PRESIDENTIAL COMMISSION ON THE
HUMAN IMMUNODEFICIENCY VIRUS EPIDEMIC

RESEARCH HEARINGS

Community-based Clinical Trials; HIV Co-factors;
Women and HIV; Behavioral Research

 

The Hearing was held at
the Metropolitan Life Building Auditorium
New York, New York

Saturday, February 20, 1988

COMMISSIONERS PRESENT:

ADMIRAL JAMES D. WATKINS, CHAIRMAN
COLLEEN CONWAY-WELCH, Ph.D.

JOHN J. CREEDON

THERESA L. CRENSHAW, M.D.

BURTON JAMES LEE, III, M.D.

FRANK LILLY, Ph.D.

BENY J. PRIMM, M.D.

PENNY PULLEN

CORY SerVAAS, M.D.

WILLIAM WALSH, M.D.

POLLY L. GAULT, EXECUTIVE DIRECTOR

COMMISSIONER NOT PRESENT:

RICHARD M. DEVOS
KRISTINE M. GEBBIE, R.N., M.N.
JOHN CARDINAL O'CONNOR

 

 

 
 

 

Research Hearing
February 20, 1988

I-N-D-E-xX

Opening:
POLLY L. GAULT, Executive Director

Opening Remarks:
ADMIRAL JAMES D. WATKINS, Chairman

FRANK LILLY, Ph.D., Hearing Chairman

Panel I: Community-Based Clinical Trials
THOMAS HANNAN, Executive Director, Community Research

Initiative.

JOSEPH SONNABEND, M.D., Medical Director, Community
Research Initiative.

CAROL LEVINE, Member, Institutional Review Board,
Community Research Initiative.

Panel IT: "Underground Drugs"
and Information Networks

MARTIN DELANEY, Project Inform, San Francisco.

JOHN S. JAMES, Editor and Publisher, AIDS Treatment
News, New York.

JOHN SCAFUTI, representing University of Central Florida
Task Force on AIDS; Orlando Gay Community Services;
Home Health Care Services, Research Division.

HERB SPIRES, Ph.D., Chairman, Issues Committee, ACT UP.

Panel III: HIV-infected Women

DENISE RIBBLE, R.N., Nurse Educator, Community Health
Project, New York.

IRIS DAVIS, M.D., Medical Director and AIDS Assessment
Coordinator, Bushwick Medical Clinic, Brooklyn.

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24

31

36

41

47

50

 

 
 

 

Panel IV: HIV Co-factors

GEORGE SOLOMON, M.D., Professor of Psychiatry, University
of California, Los Angeles.

ELINOR LEVY, Ph.D., Associate Professor of Medicine, Boston
University School of Medicine.

PETER DUESBERG, Ph.D., Professor of Molecular Microbiology,
University of California, Berkeley.

Panel V: Behavioral Research
THOMAS COATES, Ph.D., Co-Director, Center for AIDS Preven~

tion Studies, University of California, San
Francisco.

Panel VI: Sexual Behavior

 

JUNE REINISCH, Ph.D., Director, The Kinsey Institute;
Professor of Psychology, Indiana University.

BRUCE VOELLER, Ph.D., President, The Mariposa
Foundation.

JOHN GAGNON, Ph.D., Professor of Sociology, Princeton
University.

Risk Behaviors:
Research and Interventions

 

PATRICK CARNES, Ph.D., Program Consultant to the Sexual
Dependency Unit, Golden Valley Health Center,
Minneapolis.

SAMUEL FRIEDMAN, M.D., Narcotic and Drug Research
Corporation, New York.

KAREN HEIN, M.D., Director, Adolescent AIDS Program,
Albert Einstein College of Medicine, Montefiore
Medical Center, Bronx, New York.

THOMAS COATES, Ph.D., Co-Director, Center for AIDS Preven~

tion Studies, University of California, San
Francisco.

Adjournment

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94

101

108

113

131

138

143

149

163

 

 
 

 

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ry “4 f » ‘
ay m ) ‘ i!

PROCEEDINGS

February 20, 1988 [9:00 a.m.]

MS. GAULT: Good morning. Ladies and gentlemen,
members of the President's Commission, my name is Polly Gault.
I serve as the designated Federal official, and in that capacity
it is my privilege to declare this meeting.

Chairman Watkins?

Qpening Remarks

CHAIRMAN WATKINS: Good morning. Today the Commission
begins its third and final day of hearings on subjects related to
research and drug development. In the past two days we have
heard a great deal from representatives of large entitles
attempting to handle the research and drug production problems
related to AIDS, the NIH, the FDA and the private sector
pharmaceutical companies.

We also heard very moving testimony from persons with
AIDS frustrated with those systems, testimony that will remain
with us as we continue our work. Today we turn our attention to
individuals. We will hear about a research group born out of
the frustration of persons with AIDS who needed access to drugs
and others who formed underground networks to distribute drugs.

The fact that PWAs and their advocates found it
necessary to go outside the established system is a symptom of
the problems these hearing are intended to address. We will also
hear testimony about the special problems of HIV positive women
and on the subject of co-factors. ,

This afternoon we will change our focus to behavioral
research, to see if we have the tools that we need to construct
effective prevention programs to stop this epidemic.

I would like to thank this opportunity thank
Commissioner John Creedon and his excellent professional staff
for their tireless efforts on our behalf in making these hearings
efficient and possible.

I would also like to thank Dr. Frank Lilly for his
guidance through these hearings on such difficult and complex

issues, and for bringing so many of his colleagues in the science
and PWA communities before the Commission to give us testimony.

I will now turn the chair over to Dr. Frank Lilly.

1

 

 
 

DR. LILLY: Thank you, Admiral Watkins. I think that
without further ado we will continue into the planned program
this morning. Our first session will have people presenting
testimony to us about an organization formed for community-based
drug trials. Dr. Joseph Sonnabend and Thomas Hannan are going to
be our speakers. I think that Dr. Sonnabend will be our first
speaker?

MR. HANNAN: No, in fact it will be myself, Thomas
Hannan.

DR. LILLY: Mr. Hannan, I'm sorry.

Community-based Clinical Trials

MR. HANNAN: Good morning and thank you for the
opportunity to allow us to present some information about the
Community Research Initiative. My name is Thomas Hannan, and I
am a person with AIDS. I am acting as the Administrative
Director of the Community Research Initiative. On my right is
Dr. Joseph Sonnabend, who is serving presently as Medical
Director.

The woman who is seated between us is Suzanne
Phillips, a fourth year medical student who has been
volunteering her time to support the CRI and assist Dr. Sonnabend
in his research. On my left is Carol Levine, formally of the
Hastings Institute and currently with the Citizens Commission on
AIDS. She is a member of our Institutional Review Board.

Before your questions I would like to briefly describe
what the CRI is and what projects we are currently doing or are
about to begin. Dr. Sonnabend and Ms. Levine would like to make
brief remarks also before taking your questions.

The Community Research Initiative or CRI, is sponsored
by the PWA Coalition. It has an impressive institutional review
board or IRB and scientific advisory committee, and is registered
and approved by the New York State Department of Health to
sponsor well designed meaningful clinical trials of promising
AIDS and ARC treatments in a community setting, conducted by
qualified physicians in cooperation with informed volunteer
subjects recruited from their practice.

Through the CRI a larger pool of interested patients
may participate in trials and the statistical power of the
results of the studies will increase, leading to faster progress
in research. Although there is precedence for community
sponsored research, the most exciting aspect of this project is
that it originates from the AIDS community, empowering ourselves
to participate in the research that may save our lives and

2

 

 
 

 

dramatically expand the number of patients who have access to
experimental drugs.

This is a project conceived by and carried out by the
AIDS community. We are taking the initiative to seek promising
interventions against this disease in a responsible manner. The
Community Research Initiative will utilize the largely untapped
resource represented by the patients of private physicians
providing health care to the gay community and other communities
in order to seek interventions that can prevent the development
of full blown AIDS in those at risk.

It will conduct controlled trials of promising
interventions in a large group of human volunteer subjects and
design protocols from the perspective of the patient. The CRI
will also expand the number of experimental protocols under
study, including alternative treatments and areas of research
which might otherwise be neglected and are being neglected
because no financial incentive exists for pharmaceutical
companies.

Other activities of the CRI will be to provide an
opportunity for both community physicians and their patients to
contribute to vitally important research efforts, to monitor the
results of private physicians' treatment of persons with AIDS or
ARC using available drugs and natural substances such as lipids,
to help to define directions of research and to serve the
community with the latest data, and when appropriate to
facilitate the formulation of guidelines for the day-to-day
management of PWAs.

In general, the CRI will take the initiative to pursue
any research and conduct any other activity which may contribute
to the effort to learn about and eradicate AIDS.

The CRI represents a unique phenomenon. It is historic
in two respects. It is the first time in history that people
with a disease took the initiative to organize research to find a
solution to the disease. When we embarked on our pentamidine
trial it represented the first large scale trial in America to
use community physicians to collect data to be used toward FDA
approval.

In the packets which I believe the staff is going to
distribute to the Commission, you will find the list of
individuals comprising the various components of the CRI. our
Board of Governors which meets weekly, includes Dr. Mathilde
Krim; Virginia Apuzzo, Deputy Commissioner of Consumers Affairs
for the State of New York; Dr. Bihari and Sonnabend as well as
Michael Callen, a person with AIDS.

 

 
 

 

As you will read in our packet, our Scientific Advisory
Committee which generates and reviews ideas for research and from
which principal investigators are drawn for our studies includes
some of the leading scientists involved in AIDS; Dr. Donald
Armstrong, Chief of Infectious Diseases at Memorial Sloan-
Kettering; Dr. Donna Mildvan of Beth Israel Medical Center; and
Drs. Michael Lange and Donald Kotler of St. Luke 's-Roosevelt,
among others.

Our Institutional Review Board (required by law
whenever research is conducted on human subjects), and about
which you will hear more from Carol Levine, includes seven
doctors, two professors of law, religious leaders as well as
people with AIDS. I can confidently say that no other IRB
considering protocols about AIDS is as committed to protecting
the interests of subjects and to guaranteeing the equitable entry

to trials as our IRB is.

Included in your information packet is a list of 80
physicians who have private practices in New York City which
include people with AIDS and ARC. These names represent the
participating physicians who will submit patients for our
Clinical trials and who will cooperate in executing the protocols
and providing the data for collection and analysis.

The CRI has only been in existence since May of 1987,
but we already have five major clinical trials approved by our
IRB and underway. We also have other important projects in
progress.

The CRI appears to be increasingly attractive to
pharmaceutical companies for carrying out the trials of their
drugs. Our belief that we can do it quicker, more economically
and better, seems to be shared by pharmaceutical companies.

Lyphomed, one of the manufacturers of pentamidine is
funding a 200 person trial at the CRI which is already in
progress with Dr. Sonnabend as principal investigator. This was
the first trial to be approved by our institutional Review Board.

The 200 people with AIDS in the study are receiving
either 100 or 150 milligrams of aerosolized pentamidine weekly as
prophylaxis against pneumocystis carinii pneumonia or PCP, the
number one killer of people with AIDS. The subjects will receive
the drug for one year at no cost. The cost of the entire trial
will be just under $400,000.00, which includes $43,000.00
contributed by the pharmaceutical company toward general
operating expenses of the CRI. |

Now that this trial is on its feet, we have been
approached by both pharmaceuticals who manufacture pentamidine,

 

 
|

Lyphomed and Pfeizer Corporation, with offers to pay for a 500
person clinical trial for people with ARC who are at risk for
PCP.

Ortho Pharmaceuticals is paying the CRI to study its
drug, erythropoietin in a small trial. The study, which is
underway, involves patients who are anemic either associated with
the use of AZT or as a direct symptom of AIDS. The subjects will
be drawn from the practices of Drs. Barbara Starrett and
Nathaniel Pier and Dr. Starrett will serve as principal
investigator.

A third trial approved by our IRB is Dr. Donald
Kotler's protocol to test the efficacy of a therapy for
cryptosporidiosis, a devastating disease, which involves the
ingestion of cows' milk containing large amounts of antibodies as
a result of infecting the cow with cryptosporidium. Seven
patients from the practices of community physicians will be
studied. Bristol Myers is paying for all the costs of this
trial.

Our fourth trial is currently enrolling subjects. It
is a comprehensive study of AL-721 about which I will tell you
more in a moment. A parallel study of intravenous administration
of lipid which is being done nowhere else, will be considered at
our IRB meeting this Thursday.

A fifth trial which will cost approximately $.75
million has already been approved by our IRB and is about to
begin. DuPont has chosen the CRI to conduct its first trial of
Ampligen in people with full blown AIDS and will pay for the
study. The protocol which was submitted to our IRB by Dupont
originally excluded women and IV drug users. A clear example of
our IRB's concern for equitable entry to trials is its stand to
approve the trial only on the condition that the study be
expanded in the number of participants to include women and IV
drug users.

In spite of the increased costs to the company, Dupont
agreed to the conditions. This promising drug will require three
one-half hour infusions each week for the 50 participants.

An extremely important project for which the CRI is
ideally suited is our informal monitoring project or Lange
Project, so named for Dr. Lange who helped to formulate it.
Critical information about the hundreds of patients perhaps
thousands who may or may not be improving on substances which
they are currently using, like AL-721, Dextran sulfate, WOB
enzyme, or DHEA is falling through the cracks.

 

 

 

 
 

 

I am personally using these substances as well as
others and am very anxious to know whether these substances are
helping me.

| Our current Antabuse monitoring project will be
expanded to include other substances using a generic data
collection form for computer inputting. Dr. Bihari has drafted
the design for the antabuse monitoring which should establish
whether clinical improvement and increase in T4 count occurs when
patients take antabuse, a prescription drug for control of
alcoholisn.

The name Community Research Initiative should say it
all. This the AIDS community, all people affected by AIDS taking
the initiative to contribute to research responsibly. This
community is not prepared to roll over and die.

This community watched and waited as Dr. Robert Gallo
published in the New England Journal of Medicine in November of
1985, a report on in vitro findings that AL-721 appeared to be a
promising candidate for further research especially in light of
its nontoxic nature and ability to inhibit the AIDS virus. This
community watched and waited as two years passed with absolutely
no follow-up to Dr. Gallo's recommendations.

Years passed, people died, and zero research was
conducted by the government. At the same time a tiny company
with a very inappropriate name of Ethigen formerly Praxis,
claimed a patent on AL-721 and kept all other manufacturers from
supplying it but refused to make it available without medical
claims, as they could under FDA regulations, while simultaneously
pursuing drug approval.

In the meantime, people with AIDS were traveling in
wheel chairs to Israel to get AL-721, just as they were traveling
to Mexico to get Ribavirin, as I did. This community stopped
waiting for the government or the so-called patent holder to
move. This community moved. We organized an effort to make AL-
721 available by whatever means possible.

Brave people with AIDS like James Perez, a very close
friend covered with lesions, used his last ounce of energy on
this earth to produce the egg yoke extract by a labor intensive
and dangerous acetone extraction process. ‘With people with AIDS
assuming the risk of Ethigen suing for patent infringement,
manufacturers were found to provide the substance.

Thousands of people are now taking AL~721 because this
community took the initiative and still we do not know the degree
to which or even whether AL-721 works. The CRI has embarked upon
a study of AL-721 involving dozens of blood parameters to
quantify its antiviral and immune-modulating effects, if any, at

6

 

 
 

various dosages. The study, by the way, is being paid for by
money raised directly from community -- people taking action
against AIDS.

I cite the example of AL-721 to illustrate two critical
points: one, that people with AIDS should not and will not wait
until the cumbersome, time consuming process of FDA approval is
complete, especially with non-toxic substances which may help but
can't hurt; and two, that meaningful research cannot be delayed
on any substance which may prove to be effective alone or in
combination with other drugs to work against AIDS.

On the one hand we have a research establishment which
is slow and often misguided, ignoring potentially important
interventions. At the same time we have an FDA which stands as
an obstacle to people with AIDS getting as yet unapproved AIDS
drugs.

The CRI provides an answer to the two part problem I
have been describing. Large numbers of people with AIDS and ARC
will be receiving drugs which they could not otherwise access
while they are contributing to data about those drugs by
participating in controlled studies.

We hope that New York City's CRI will serve as the
prototype for many CRI's in other cities with large populations
of PWA's. We are anxious to export the concept of community-
based research to other cities and have prepared how to packets
to facilitate other communities in starting up their own CRI's.

Dr. Krim has convinced AmFAR to fund a program to
support CRI's and provide seed money to create CRI's in other
cities. This program is called CARE - Community AIDS Research
Endowment.

Finally, I cannot stress too strongly that the research
conducted by the Community Research Initiative is just as
legitimate as anything done at the National Institute of Health
or anywhere else. Our data is just as meaningful and our methods
at least as correct.

For instance, the protocol for our 200 person trial of
aerosolized pentamidine was submitted in advance to the FDA for
their approval of the study design. Our data will be analyzed
with the data from the San Francisco General Hospital Study with
Dr. Bruce Montgomery as principal investigator. Our combined
results will contribute to a faster approval of pentamidine in
this form and establish the effective dose.

Professor Peter Duesberg, who will be speaking before
the Commission a little later today, made a very amusing slip of
the tongue recently. After a public forum sponsored by the PWA

7

 

 

 
Coalition, he approached a person from ACT UP who was wearing a
button which read "Silence Equals Death," but he mistakenly read
it aloud with is charming accent, "Science Equals Death."

We cannot allow science to equal death. We must insist
that research proceeds expeditiously and properly, exhausting
every lead.

We have a responsibility to do it right. We have a
responsibility to those we have allowed to die, like my lover who
died in my arms this month, and we have a responsibility to those
that still have a chance to live. I guarantee that the CRI will
accept the responsibility of doing its part in finding a
solution if one is possible to find. And I guarantee as well
that people with AIDS will hold us all accountable to provide the
very best that we are capable of, because that is precisely what
it is going to require.

Thank you for hearing my testimony. I would now like
to introduce Dr. Sonnabend who has a few remarks.

DR. SONNABEND: I am grateful to have this opportunity to
tell you something about the Community Research Initiative and
how it particularly can contribute to the development of
effective treatments against AIDS.

Of the many emergencies that comprise the AIDS crisis,
the need to develop effective treatments is maybe the most
pressing and it is in this area that the CRI can make a
significant and special contribution. The need to rapidly
develop effective treatments means that we have to test many
different treatments and combinations of treatments
simultaneously. This is going to require access to a large
population of patients with AIDS and AIDS-related conditions as
well as, of course, an appropriate administrative structure that
will enable the trials to be conducted in a proper fashion, the
data to be gathered efficiently and the analysis done well.

Tom Hannan has just described something of the
structure that we have in place in order to conduct trials in
this fashion. The Community Research Initiative can tap into the
practices of physicians who are providing care to individuals
with AIDS in the community and this is how the CRI really
started. It started with the idea that physicians here in New
York City with large practices who see people with AIDS could
provide a great resource for doing treatment research.

We realized very early that the group of patients in
these practices are largely white gay men. Our Institutional
Review Board at its second meeting -- this is almost a year ago
-- addressed this issue of equitable entrance into treatment
trials for all people with AIDS. I think this illustrates

 

 
 

 

already a responsiveness ‘and responsibility that is an advantage
-- I think peculiar to a community-based research endeavor in
contrast to research that is conducted in medical centers.

One only has to look at the demographics of the large
multi-center AZT trial to see this contrast. There were
virtually no women, no black men who were enrolled at any of the
study treatment centers.

As a community-based organization sponsored by people
with AIDS, the CRI is particularly sensitive to their needs. The
importance given to the issue of equitable entrance is not the
only example of this sensitivity. The issue of pneumocystis
pneumonia prophylaxis and the use of placebos in critically ill
individuals are two.further examples.

As Tom Hannan said, pneumocystis pneumonia is the most
frequently occurring opportunistic infection that is seen in
AIDS. This infection is almost definitely preventable although
the kind of data that is needed in order to prove efficacy has
yet to be obtained. It is of course, of great importance to
obtain this kind of proof of efficacy.

It is also important that people with AIDS are not
denied access to an intervention that will most probably prevent
pneumocystis pneumonia even while trials establishing efficacy
are underway. The CRI is meeting both these needs; the need to
do a controlled trial and the need to provide patients with
access in other trials to a means of preventing pneumocystis
pneumonia.

As Tom Hannan mentioned, we have a formal 200 person
trial that has been underway since the beginning of the year.
This is a formal study of the effect of aerosolized pentamidine
in preventing pneumocystis pneumonia. As Tom Hannan mentioned,
the data obtained from this study which will last for a year will
be combined with the data obtained from a similar study that is
underway at the San Francisco General Hospital in providing
evidence regarding efficacy and longer term safety of this
particular intervention.

Now at the same time as conducting a systematic study
on PCP prevention, the CRI when it considers other trials in AIDS
patients has required that PCP prophylaxis is not denied to trial
participants. Of course, this means that the occurrence of PCP
in a particular trial can no longer be used as an end point.

When one is testing a particular drug for efficacy, you can no
longer look at the occurrence of PCP in a placebo group as an end
point in such a trial. This simply means that the studies are
going to be much more difficult to design but certainly not
impossible to design.

 

 
 

 

I should also point out that the move towards
pneumocystis pneumonia prevention has originated largely in the
community of people with AIDS. I believe it is largely in
response to pressure from this community. It is because of this
pressure that the use of a life saving intervention is now being
offered to more individuals.

In addition, the CRI has shown that the wider
availability of such an intervention off protocol is not
incompatible with the systematic gathering of data that is
required to obtain proof of efficacy. These can be going on
simultaneously. In other words, while we are doing the formal
studies we should not be denying other individuals an
intervention that in all likelihood will prevent them getting
what may be a fatal infection.

On the issue of placebo controlled trials, the CRI is
also responsive to the community of people with AIDS in resisting
the use of placebos in trials where the life expectancy of the
individual may be shorter than the duration of the trial. Of
course, there are places for placebo controlled trials but
critical illness with a short life expectancy is not one of
then.

There are other ways to conduct controlled trials that
do not require the use of a placebo. For example, the CRI is
about to begin a blinded trial comparing two doses of active
lipids analogous to AL-721 and Tom Hannan did say something about
this particular trial.

There is a further advantage that community-based
trials offer in comparison with those conducted in medical
centers. This relates to the fact that people with AIDS who are
trial participants at medical centers are frequently taking
numbers of interventions on their own initiative. This is much
to the dismay of the investigators who are aware that
individuals in their trials are taking substances and are even
resorting to drug testing trying to determine whether or not
these individuals are taking other interventions.

People of course do not admit to this because to do so
would exclude them from entrance into the trial. The CRI trials
are more likely to acknowledge this reality, the reality that
people are indeed taking other substances and to design the trial
around this reality. I believe it is possible to do. There are,
of course some instances in a specific trial, where the use of a
particular substance would make it impossible to interpret the
results. Overall, I believe that it is possible to design the
trial around the fact that people are taking additional
interventions as long as one knows what these are and designs the
study around this.

10

 

 
J

The conduct of trials outside medical centers is a
novel approach but it is certainly not unprecedented. Together
with Dr. Krim I founded the AIDS Medical Foundation some years
ago. One of our tasks was to conduct the kind of comnunity-
based research that the CRI is now undertaking. Our experience
in establishing an Institutional Review Board and approving and
sponsoring trials in a community setting indicates that such
trials can indeed be successfully conducted.

In fact, many of the CRI IRB members were also members
of the AIDS Medical Foundation IRB and thus have experience in
reviewing community-based trials.

I would like to end on a personal note. I ama
microbiologist and until 1978 most of my professional life was
spent in a research laboratory with some clinical experience
limited to infectious diseases in a hospital setting.

It is from this background that in 1978 I started to
see patients in a private practice in Greenwich Village in New
York City. Many of these patients were gay men who at that time
already manifested a variety of hematologic abnormalities which
in retrospect were the first and earliest manifestations of AIDS.

Thus, I have had the opportunity to observe this
epidemic from its onset. My views about AIDS have been shaped by
this practical experience of seeing many, many patients with AIDS
from the onset of the epidemic, and also my research background
as a microbiologist.

The view that I have about AIDS is that the causes of
this disease remain unknown. I do not believe that HIV is the
cause of AIDS. In my view, and of course this is not the CRIs
view it is my personal view, but I will mention it now because I
believe that the premature acceptance that HIV-1, and now HIV-2,
cause AIDS has resulted in a commitment of almost all treatment
resources towards the development of anti-retroviral treatments.
While of course such work on anti-retrovirals has to go on, it
should not go on to the exclusion of other approaches. I
believe that the CRI is less likely to be constrained by the
limitations that have been seen in previous treatment research.

 

For all the above reasons, I believe that the CRI and
hopefully other organizations similar to the CRI which will come
into being in other cities in the United States, that the CRI
represents a very significant hope for the future in bringing
larger numbers of individuals into a diversity of treatment
trials and it deserves all the help and support that it can
receive.

[The prepared statement of Dr. Sonnabend is included in
the Appendix. ]

11

 

 
 

 

MR. HANNAN: Would the Commission indulge us for a very
brief remark by Carol Levine and then we would be receptive to
answer your questions?

DR. LILLY: Ms. Levine is not a scheduled witness but we
can do that. However, I would like to point out that some of our
most useful sessions are the question and answer sessions, and we
would like to reserve as much time as possible for that.

MR. HANNAN: Of course, I appreciate that. I am
grateful.

DR. LILLY: I would appreciate it if you would make it
brief so that we could move to the questions.

MR. HANNAN: Certainly.

MS. LEVINE: Yes, I will be very brief. My name is
Carol Levine. I am Executive Director of the Citizens Commission
on AIDS. I will be testifying before you at another time in
another city on another subject. I am here as a volunteer. I am
a member of the Institutional Review Board of the Community
Research Initiative.

You all, I am sure, know that the IRB system is in
place about 20 or 25 years and is required by Federal regulation
and state law. This IRB operates under all of those regulations
much as other IRBs do. It looks at risk benefit ratio, it looks
at the informed consent process, and it looks at the selection of
subjects. You've heard about that.

Why this IRB is different, you have heard one reason,
and its particular concern with equitable access to trials which
we have discussed at great length. It is also different, I
think, because of the presence on the Board of physicians who
treat people with AIDS and people with AIDS. That has made a
difference in the evaluation of the protocols and in some cases,
changing the requirements and reducing the number of tests, being
sensitive to the burdens of the research even though it is
considered a benefit and it is a benefit to be in a research
protocol.

It also involves additional blood tests and other
interventions. We have been very sensitive to that and the
people with AIDS have made that very, very clear to us. For me,
why do I do this and each of you have heard personal reasons, I
really have a firm belief that the desire and demand to have
access to clinical research must be channeled in a very
productive way. This is a resource that we must use productively
not only in the hope that it will benefit those individuals who
are in the trials, but that it will lead to generalizable
research for others.

12

 

 
 

 

I have a second belief that is extremely important,
that local community-based efforts should be supported in
research and education on all levels. This immense problem
cannot be solved unless we really deal with communities where
they are.

Finally, a very firm belief based on what I have heard
for seven or eight years that there is no single answer, that
there will be a number of research findings that taken together
will make it possible to treat this disease. This kind of
initiative does help that. It should not been seen in any way as
a substitute for Federal, State and large scale interventions and
initiatives.

It can provide additional important information. Thank
you.

DR. LILLY: Thank you. I would like to start the
questioning with Dr. Lee. I would hope that during the
questioning that we could come to some perhaps slightly more
concrete idea of in what way the Commission can make
recommendations to the Administration that will be of use to you
and organizations like you.

DR. LEE: Thank you, Dr. Lilly. I have three sets of
comments, and I would like the panel to keep them in mind and
then come back to me with your responses.

First of all, your inclusion of active drug addicts in
your research studies, I believe is a bad mistake. For whatever
percentage of drug addicts you have in your trial, you will have
that percentage of completely flawed material available to you.
Anyone who has ever worked with drug addicts knows, especially IV
drug addicts, that they are unpredictable at almost the 100
percent level.

If you have good medical people on your Advisory Board
and you do, I am sure they will dissuade you from including those
people in your trials or collecting data in an unsegregated
manner.

Number two, your community-based research initiatives
are being strongly pumped by NIAID, by Dr. Hoth. We heard a
great deal from him last night about that. He was, as you know,
transferred out of cancer work into the AIDS effort. He is one
of the best people in this country, he is strongly on your side,
and I would hope in the next six months I would hear more
cooperation from your end instead of this constant bashing.

A last comment, you brought up this business of
Ethigen. We heard a very similar thing yesterday from HEM

13

 

 
 

 

Research. The dragging of the feet when one has a drug on tap
for personal reasons, or private reasons, or economic reasons is
something that certainly this Commission wants to address. If
there is more detailed material available on this type of
activity we would like to know about it.

One additional thing. The companies that are
supporting you seem to be getting these drugs approved in some
way and giving them to you. We have been told that the companies
are not having any hold up here at the FDA level. Is that true
or not true?

MR. HANNAN: In the context of the controlled trial
there is no hold up. My reference to people with AIDS trying to
access other substances was with regard to products like dextran
sulfate which may not be in a controlled study at this time but
people with AIDS may want to access then.

If I may respond to your remarks and maybe Dr.
Sonnabend is much more qualified that I, would also like to
respond. I am deeply distressed by your remarks that our trials
would in some way compromised because we include IV drug users.

I am not a scientist and I don't know the details of
how well science is properly conducted. It is not my job at the
CRI to do that. We have a search currently for an administrative
director to replace me who is more qualified with FDA
regulations, et cetera. I am a person with AIDS who took the
initiative to get this started and other people on this panel are
probably much more qualified to respond to your remarks in terms
of the science.

If Dr. Bihari, who is on our institutional Review Board
and Board of Directors were here to respond, he is the Director
of Addictive Services at Down State Medical Center and has on
many occasions, said that there are populations of IV drug users
and former IV drug users who could in fact be the most very
responsible participants in trials.

People in methadone centers, et cetera, who are
anxious. People with this disease have their lives on the line
and they are going to cooperate. There are IV drug users who are
participating in our trials currently and who are coming every
other week as they are supposed to for the pentamidine trial.
Without breathing this pentamidine they are in tremendous risk of
getting pneumocystis pneumonia. We have IV drug users who are
now former IV drug users because they are taking seriously
concerns for their lives. They are taking responsibility for
their lives, perhaps in some cases for the first time.

Secondly, with regard to your feeling that you have
been listening to remarks about the CRI positively which seem to

14

 

 
 

 

be. strongly pumped by the NIH, I am very grateful for their
positive remarks with regard to the CRI's activity. In fact, we
have met with Dr. Killen on many occasions and he has been very
enthusiastic about a cooperative effort.

If I seemed to be constantly bashing the system it is
because heretofore things have been going slowly. I have
tremendous optimism that the NIH especially insofar as it will
cooperate with the Community Research Initiative, will be making
great progress.

When you refer to Dr. Hoth coming over from the NCI
where he has some experience with a community-based research in
cancer research and Dr. Killen, I am quite enthusiastic and
confident that we are going make progress hence forth.

My remarks referring to what trouble we are in today
are because things have been so sluggish.

DR. LEE: My life has been spent doing drug studies in
cancer patients. There is not a cancer study anywhere that will
include active drug addicts, because their participation is too
unreliable, and therefore, the data is too unreliable.

What we do is, we will treat these patients "off
protocol," with the drugs or radiation, but we do not include
them in our statistical data. Now, we are in a very difficult
situation. So much needs to be learned about HIV in immune-
compromised, drug addicted individuals. And while I am
sympathetic to your wanting to include them, any complicated
protocol in which active addicts are included will be difficult
to evaluate, at best, especially a small study like yours.

MS. LEVINE: The IRB chose to put the conditions in
this way: the ability to comply with the protocol is a valid
criterion; but that we would not consider simply being an IV drug
user automatically exclusionary. It would be up to the
investigator to determine on an individual basis whether a person
who five years ago was an IV drug user and is no longer, that
person might be perfectly able to comply.

In fact, the importance is the population of the future
will include many people in this category. It is important to
know how these drugs act in that group. I would also like to say
as a fourth year medical student doing my clinical rotations at
Brooklyn Hospital, that I am approached many times by patients
who are not necessarily themselves IV drug users, but who are
diagnosed as having contracted -- who believe they have
contracted AIDS through sexual contact with people who had AIDS.

_ Many of these are married women with children. They
cannot afford to tap into the network in Manhattan which can be

15

 

 
 

 

very expensive. They beg me with tears in their eyes after they
have asked me for what arrangements they should make for their
funeral and the disposition of their children, do I not know of
some sort of research protocol that they might not be able to get
into. The desperation and determination, I have seen many lives
turned around by this disease, Dr. Lee.

Many people re-evaluate choices that they had made in
the past that they now view as mistakes and want very much to
live.

DR. LEE: Emotionalism is not a substitute for
evaluating these drugs properly.

MR. HANNAN: Dr. Lee, our institutional Review Board
has some very qualified people, extremely qualified, and serious
consideration entered into the decision to include IV drug users
in the particular trials. I am confident of their decision.

DR. LILLY: I would like to go on to another question.

MR. CREEDON: I would like to comment on it, because I
for one, felt good about the fact that the CRI was including IV
drug users and I would think that there would be some way of
having a statistical method, even though you are including them
you can report results both with them in and out. I would think
there would be a way of approaching it, and I would certainly
urge that you do it if you can figure out a way of doing it
without compromising the study.

DR. LILLY: I would also say that in fact since there
may be possibly differences between the responses of IV drug
users and gay males for example, that it would be a very good
idea to do one's best to collect data on that population.

MR. CREEDON: Absolutely.
DR. LILLY: Dr. SerVaas?

DR. SERVAAS: I am impressed with what you are doing,
because I think anyone of us at the table who had AIDS would
probably be doing the same thing. I really believe that. I
think that we can help you because I understand Dr. Lee, where he
is coming from. We have tested a number of former drug addicts
who are now completely turned around, completely responsible
people who are AIDS, HIV positive.

If you send to the Commission where we reach you, if
you are nationwide, we could help you get these very responsible
rehabilitated former drug addicts who now want to live as you
have pointed out, want to do everything right and have a great
deal of interest and are not going back to drugs.

16

 

 
 

 

f
‘

I believe we could help supply these HIV positive
individuals who were former drug addicts from around the country
, if you will give your address and information to the Commission.
I got the impression that you are nationwide; is this right? You
have now locations in other cities?

DR. SONNABEND: We are attempting this.

MR. HANNAN: We are attempting to create Community
Research Initiatives in other cities, as I mentioned. Right now
the Community Research Initiative in New York City is the only
one with trials underway, and we hope to serve as the prototype
for other centers and are trying to facilitate other groups in
other cities getting started.

I would like to continue with the IV drug users just
very briefly, because I don't want to dismiss Dr. Lee's concern
for the compromising of the science in trials. I don't believe
that the CRI would ever allow science to be compromised just for
the social responsibility of including IV drug users.

I believe it is possible with a creative approach. I
am quite certain that we should stratify the information that we
are collecting about IV drug users, because as Dr. Lilly
indicated, there may be physiological differences in the way this
treatment progresses in different groups including women and IV
drug users.

It is essential -- this is the only way that people in
these groups can be treated. Treatment for AIDS today is with as
yet unapproved substances and that means controlled trials.

DR. SONNABEND: Just one further point about drug
addicts and their participation in dur trials. The future of
this disease the way it is moving, is largely as Carol Levine
said, into this population. When that happens I believe the
support for AIDS research is going to decline. So we have a very
important moment now when we have the ability to reach out and
make connections with this population, that we should utilize the
time very efficiently in linking to the drug addicted community
and bringing them into trials now before the mood and climate
shifts.
DR. SERVAAS: Are you doing things with people who are
HIV positive before they get ARC? Do you have any protocols?

DR. SONNABEND: We don't currently have a protocol for
that.

MR. HANNAN: None of the five protocols that we have in
place currently are specifically to look at agents working in HIV

17

 

 
 

 

positive. Our informal monitoring project which I described,
does of course include all people in various stages of this
disease, and will be looking at large numbers of people who are
doing various interventions including HIV seropositive who are
otherwise asymptomatic to see whether those people over the long
term do not become symptomatic by using these agents.

It certainly is our intention to be doing protocols in
the future which would include those people. It is central to
our concern.

DR. LILLY: Mr. Creedon?

MR. CREEDON: I think one of the great strengths of our
country really is the whole concept of competition. I think what
you are doing is introducing an element of competition into the
realm of ideas on how to deal with the AIDS problem. I certainly
commend you for what you are doing and I say right on.

I think it is very frustrating to hear about this AL-
721. I think we ought to find out about why it was identified
by Dr. Gallo two years ago and nothing was done about it. There
has to be some kind of an explanation for that.

The other thing, I would urge you and I'm sure the
Chairman will, to let us know how you think we can help. I would
suggest that you might consider applying to the insurance
industry for some help too.

MR. HANNAN: Very good suggestion. We thought of it,
thank you.

DR. LILLY: Dr. Walsh?

DR. WALSH: I, too, have been very encouraged to hear
what you all are trying to do this morning. I am doubly
encouraged by the attitude that we heard yesterday, particularly
from the FDA because if you were not here yesterday, Mr. Hannan,
I think that you should be alerted to the fact that Frank Young
really said his door personally is open to do everything that he
can to expedite the clinical trials.

I think that when we hear things like this we ought to
quick take advantage of them before they have a chance to change
their mind. I really feel that you should contact them right
away and tell them what you are doing.

I am sure, as I think as Dr. Lee suggested to you on
your IV drug users, that in the interest of your own research and
in the interest of your own patients and colleagues that if you
find somebody violating protocol you will put them in a different
column. You may not drop them out but you will put them ina

18

Bc

 
different column, just like Dr. Lee does as Sloan-Kettering so
that you would have some collateral information.

I think any good scientist does that. Dr. Sonnabend is
going to do that. I am sure he's not going to let your protocol’:
be disturbed.

I have one question and then I am going to as you to
help us. The question that I have is I was not clear -- I think
you said -- I know in your paper that you are doing placebo
trials on people without AIDS that are not in danger of death.
But are you doing some of these drug trials at all on just
seropositives that are not people with AIDS to see whether
anything is happening to change the course of the disease? I
think I heard that you are, but I wasn't sure.

MR. HANNAN: No. In fact, we don't have a formal
protocol approved by IRB yet. We have only been existence since
late 1987. It is our greatest anticipation of course.

DR. WALSH: The other thing that encouraged me so much
is that you are getting financial assistance from the
pharmaceutical companies. Now again, this is something that I
would urge you continue to do. If we are getting into bashing
from a different framework it is much better to go to them for
financial support for your studies because they are very anxious
to have them done, than to worry about what the ultimate cost
might be later. You can bash about that later but don't
antagonize then.

Go to them for help because you are helping them and
they will help you. The request that I have from you is can you
give us either today or in writing, some concrete suggestion of
what we could do to help expedite more community-based trials.
We do'have concern, and I think some of us expressed it
yesterday, that with all the good intention in the world NIH can
restrict what drugs are to be tried.

You have to remember that these men come -- and Dr.
Sonnabend will appreciate this especially -- from a scientific
trained way of approaching things. They get on a hot drug and
that's the one. The think here we have an answer and we are
going to push this one all the way until we find something
better.

There has to be a way for us to get them to perhaps be
more relaxed somewhat with their funding or with their ability to
put out study funds, to support more clinically community-based
trials in the way in which you have organized them rather than
just the university-based trials at these so-called ATEUs that
they have.

19

 

 
 

 

The pharmaceutical companies are having trouble with
the ATEUs and they testified to this. They feel, I am sure your
method of clinical trial is much closer to what pharmaceutical
companies normally do in clinical trial. I think they would be
sympathetic to this. Perhaps we as a Commission as well as them
could help you expand this concept.

We are very conscious that your concern with people who
are dying now -- this is a different disease than say the longer
range illnesses that we see, cancers and heart diseases, where
you can take a little more time with research.

You have too many people dying too quickly. I think
that everyone is interested in finding an answer but without
violating serious scientific protocol, and I don't think you want
to do that. I know you don't want to do it, because you are
going to jeopardize yourselves if you misapply the use of drugs
or combinations of drugs as you know you can set back treatment
rather than advance it.

Your purpose is to advance and help the PWAs and not to
set them back. Let us know as specifically as you can, what we
can do to get more support and more interest and more
consideration directed to community-based trials, modeled after
your experience.

MR. HANNAN: Dr. Walsh, thank you very much for your
suggestions. We intend to provide to the Commission in writing,
details of the specifics and how you could help us and what our
needs are. Specifically right now, I can tell you that you could
reinforce your unique position of power in the report that you
come up with. You could reinforce what already is apparently
happening; that there is support for this kind of idea.

As Dr. Lee already indicated, the NIH appears to
already realized the potential of systems such as this, as
alternatives and systems which can cooperate with the NIH. Dr.
Hoth has already gone on record indicating that he would like to
support the CRI financially and use its resources as a tool for
the NIH work.

You can help us a great deal by encouraging that in
your report.

DR. WALSH: We want to turn those words into action.

DR. LILLY: A very quick question. Have you received
any government support whatsoever?

MR. HANNAN: We haven't formally requested. We have
had meetings with Dr. Killen and he has made indications that it

20

 

 
 

 

would be possible in the future, but I am not going to bash the
NIH for not giving us money.

DR. WALSH: Keep in mind incidentally, that although
the FDA is normally not a granting agency, Dr. Young did indicate
yesterday that they have given four modest support grants for
some kind of trials. I frankly don't recall what they were.

This was very unusual.

But apparently they have a small pot of money and you
are not talking about a great deal of money when it comes to the
granting cycles. It might pay to see number one, what he can do
and number two, what he could influence.

MR. HANNAN: Thank you for the suggestion. That is the
reason that I am being replaced as Administrative Director.

DR. LILLY: I would like to go to Dr. Crenshaw because
we are running very late. I'm very sorry.

DR. CRENSHAW: In relation to the inclusion of IV drug
abusers issue, in drug research not related to AIDS that I have
done in California, one of the things that we routinely do is
drug screens because you never know who is clandestinely taking
drugs. I don't know if you are already including this in your
protocols or not, but that is helpful in monitoring these issues
so that you are not surprised.

I am also very pleased to see the interest in antabuse,
which I think raises questions that can rapidly and
cost-effectively answered relatively quickly.

The thing that I would like to ask you and both to help
us with reflect upon -- although I know you've given it a lot of
thought -- as leaders and representatives for the PWAs, you hold
in your hands enormous power relating to the manner of spread of
the disease because we all agree the major motive spread we are
concerned about is sexual transmission.

What exactly do you advise in relation to sexual
behavior to prevent the spread, and how do you advise someone in
spite of the advice that you give continues to be sexually active
or not warn their partners or not use protection. I know it is a
struggle for all of us.

What are you doing; what is the current approach?

DR. SONNABEND: As a reSearch endeavor it hasn't been
our role to -- you are asking if the CRI has a role in terms of
giving specific advice to people. We have not assumed that role,
but I think the advice that the CRI might be seen to be giving is
that of the People with AIDS Coalition. That is that there is a

21

 

 
 

 

concept of safer sex, of the use of condoms and this is
promoted.

Information about safer sex and access to condoms and
information about their use is, in fact, actively promoted.

DR. CRENSHAW: I guess the comment that I would then
make is that you have a unique opportunity and even though it may
not be perceived as traditional in research from my bias,
behavior research and the issues of preventing transmission of
this disease will help you in the long run so much in the people
you are trying to protect.

The challenges that this AIDS epidemic poses, if you
can break tradition a little and see what it is that you can do
in the role of prevention since you have the opportunity in the
patients that you are working with. I think it would be very
valuable.

DR. LILLY: Dr. Primm.

DR. PRIMM: I would just like to commend the panel on
their stand about including intravenous drug users in the studies
that you do. I find that they are awfully responsible and
particularly when they are infected with the virus or, indeed,
when they have full-blown disease. And I want to let you know
that you can call on me and get some responsible intravenous drug
users who are in treatment from my program at any time you want.

It's good to see you, Suzanne.
DR. LILLY: Admiral Watkins?

CHAIRMAN WATKINS: Well, I, too, am enthusiastic about
what you are doing. I think you are at the heart of perhaps a
concept in the nation that needs to be critically looked at, not
only for the near-term, but the long term as well. I believe
that when we have a rapidly moving emerging crisis of this type
that it is very important to mobilize the community-based
initiatives in the country and pull them together as you have
done.

I think you have done it in a very responsible way. I
think you are a tremendous adjunct to what can and should be done
at the national level as well, and what I am thinking of, I am
wondering if, Mr. Hannan, you could give us a little better
picture on how the Commission might ensure that there is some
potential to have a linkage, some kind of a linkage with the NIH
in perhaps a little more -~ maintaining the independence on the
one hand, but technical link, because you are so treatment-
oriented with scientific data being supplied, which is very
necessary in this crisis, and we have seen the importance of

22

 

 
 

 

sensitivity to immediate treatment to people with AIDS. At the
same time we want to get scientific data, it seems to me you are
providing a nice sense of balance between the two different
approaches to clinical trials, and so I commend you for it.

I wonder if there might be a separate initiative, for
example, for direct NIH grant programs to this community-based
concept of research. Is there something there that can be done
to enhance not only the value of CRI, but perhaps CRI tentacles
that would be elsewhere in the country, and begin to move in that
direction to test your approach to clinical trials.

At any rate, it would be useful if you could give us a
little better idea of how there might be a coupling there for the
near term and for the longer haul as we begin to look at some
downstream concepts that might be a lesson learned out of this
infectious disease that we need to leave for the nation.

So would you be willing to do that and give us some
feel for whether or not there are some things that we can do
right now perhaps to enhance what you are doing, and to get a
better coupling, between NIH and you and, at the same time, give
us an idea of how this might be looked at for the longer haul?

MR. HANNAN: Admiral Watkins, it is incumbent upon us
to make specifics to the NIH, which we have informed them that we
will do. They have substances which they have not yet moved on,
which they have in the high priority classification, such as
dextran sulfate. We are in a unique position with this simple
substance, which is taken orally, to monitor and do a serious
trial very quickly.

In fact, the PWA health group, about which you have
heard before, which makes lipids and other substances available,
is making dextran sulfate available so that the time is right
now, before too many people are doing it and we don't have data
on it, to get a controlled study in place.

Now we could approach the NIH for that particular
project or hosts of other projects. As I mentioned, the informal
monitoring project of hundreds, perhaps thousands, of people
doing various substances is something that is not being done
anywhere else, and direct funding by the NIH for that project
would be money well spent and, in fact, it's been discussed with
Dr. Killen.

DR. SONNABEND: Maybe, Admiral Watkins, there was
something else you may be suggesting, which is how can we link,
in terms of sharing data or having some kind of dialogue.
Because, as you suggested, we represent an alternative or a
rather different way of going about this business of treatment
trials, and there would be some value if in fact there was some

23

 

 
kind of dialogue in a formal fashion that could be set up
between what we are doing and what future CRIs are doing, and the
research that the NIH itself is sponsoring. And it would be a
mechanism for a dialogue, the exchange of information, to our
mutual benefit.

CHAIRMAN WATKINS: Thank you very much.

DR. LILLY: Thank you, gentlemen and ladies, for your
participation this morning. .

"Underground Drugs" and Information Networks

DR. LILLY: Our next panel will present four
individuals who will expand upon some information that we
received yesterday as well. It would appear that in their search
for treatment for their disease, PWAs have felt that they needed
to resort to information-gathering on their own, and the
development even of systems of finding drug treatments not
through the regular channels.

We will now have a panel consisting of four individuals
who are going to explore this area for us. The first speaker
this morning is Mr. Martin Delaney, who comes to us from San
Francisco, where he has been in charge for some time of the group
called Project Inform.

Mr. Delaney.

MR. DELANEY: Thank you, Dr. Lilly.

I would like to begin by thanking the Commission for
inviting us to speak here today. I don't know, but some of you
may be aware of the fact that I was one of this Commission's
harshest critics when it was first formed. I had some strong
comments to make in the media, and I must say that since that
time I have had to eat my words, and I have been quite impressed
by the fairness and objectivity with which you have proceeded.

I was particularly impressed with your initial report
because it simply did not live up to some of the nightmares that
I had had about where this Commission was going. So I am glad
that we are in a cooperative mode at this stage.

Now, unfortunately, in my testimony today I am going to
have to say some things that I feel are critical, and I hope I
can do it in as constructive a manner as possible. I don't want
to feel that I am up here to bash the federal authorities.

24

 
 

 

On the other hand, I sat here for hours yesterday
. listening to testimony that I felt was vastly removed from the
reality that we have experienced in the community.

I would also like to begin just by following up on the
last presentation. I know we heard about NIH's interest in
supporting community research. This Commission should know that
San Francisco has had a community-research initiative in
operation since 1985, perhaps a more conservative group than the
one we talked about here, but as recently as last week that
commission, that consortium, was denied funding by the NIH.

DR. LILLY: What is the name of that group?
MR. DELANEY: Pardon?
DR. LILLY: What is the name of that group?

MR. DELANEY: That's the County Committee Consortium
operating out of San Francisco General.

Based on the testimony that we heard yesterday, it is
probably evident to the commission right now that the AIDS
community exists in a very different universe than the one that
federal officials presented.

They claimed before us yesterday that there are no
statutory obstacles preventing access to helpful drugs; that no
one has ever been denied access. We in turn have experienced a
system in which we are denied access to dozens of drugs which
have shown promise in early trials.

They claimed that drugs may be made available on the
basis of many possible criteria, including in vitro data, animal
studies, Phase 1 data, even the structure of a drug. We have
experienced a system which has denied treatment IND for drugs
which have met all of those criteria.

They see a system which is bending over backwards to
make drugs available to people in need. We have experienced a
system which has delivered a single drug.

: They see a wealth of new treatment INDs coming just
around the corner. We have heard that same promise virtually
every month for the last year and have not seen the results of
it.

They describe a utopian vision of efficiently-run
agencies which are squarely on top of the problems we face
together. We instead yesterday saw round after round of slick
presentations created by public relations specialists and, in

25

 

 
 

fact, they were the same presentations we have heard for the
last two years.

I have to ask, does the Commission seriously believe
everything it has heard from the Federal agencies over the last
two days. I desperately hope not. It has in effect been asking
the fox how things are going in the chicken house.

[Applause. ]

MR. DELANEY: And in contrast to Dr. Young's point
yesterday, I do not say this to raise funds for my organization.

MR. CREEDON: We are also asking the chicken.

MR. DELANEY: Yes, and I do appreciate that, as I said.
I think it's wonderful that you are hearing both sides of this.

FDA yesterday attempted to have you believe that the
problems exist primarily as a perception gap between the AIDS
community and what in fact has been done for it, that we simply
aren't well informed. That is simply not the case.

The member of the AIDS community who testified before
you yesterday and the people who spoke here today and will follow
me this morning in fact are among the 10 or 15 most knowledgeable
people in the country on what has been done and how the system
actually works.

These people have spent together many dozens of many
years attempting to make the system on our behalf. We have
followed their procedures, we have tested their systems, we have
filled out their paper work, we have repeatedly listened to their
same presentations over and over again, and in all honesty, I
must say we conclude that they are not telling you the whole
truth, at least not as it impacts upon us.

The facts are these:

To date, only AZT has been made available in general
under the federal process. A few days ago Trimetrexate was
released for a few hundred patients with PCP. Other than that,
all other drugs have been turned away by the regulatory process,
and most have been ignored in the testing process. The rest of
what you have heard is mere talk.

Manufacturers across the country fear using the
treatment IND process because of the manner in which it has been
managed by FDA. We have heard this repeatedly from
pharmaceutical companies who tell us they won't in a cold day in
hell attempt to use the treatment IND process. Their attorneys,
everyone else, is telling them that to use that process is an

26

 
 

 

invitation to trouble, both with FDA and, as you recognized
yesterday, with legal issues as well.

Therefore, in our experience in the community, this
lack of. access to treatment has created the vast underground of
smuggling, manufacturing and distribution of unapproved drugs. I
don't pretend to you that this is all a wonderful or glorious
thing. As they pointed out in the last presentation, we don't
know whether much of this is helping or hurting, yet it goes on
largely because people feel that it works. And I must say that
people are very quick to dismiss products that they find that are
harmful or worthless.

For years we have seen what appeared to be clinical
improvements brought about by the use of products that FDA will
not recognize and NIH will not test. I don't think we are crazy
because our lives depend upon making the right choices.

Today great numbers of HIV infected people who have
experimented with both the approved solution, AZT, and these
unapproved solutions have in fact gone on to choose the
unapproved solutions.

You have probably heard over your various hearings that
many people believe that those facing death should be permitted
access to any treatment which is shown to be safe, whether or not
that treatment has been proven effective. Many find this
argument particularly compelling where no proven treatments are
available.

Many others believe that life-threatened people and
their physicians should be permitted to decide what risks they
undertake; whether that risk be to their health or merely to
their wallets.

Currently the power of making that choice rests solely
in the hands of federal bureaucrats far removed from the agonies
of fatal illness.

Project Inform as a group concurs with this view that
people ought to be given that right, particularly people who
face life-threatening illnesses, that it ought to be up to them
and their physician to decide what choices they can make.

However, we realize in a practical sense that it would
require enormous changes in the American system of medicine to
make that a reality and, therefore, I am here today to suggest
some other things that fall perhaps short of that, but which I
feel would be possible to achieve within the current structure.

We feel basically that the treatment IND regulation as
described by FDA was a major step in the right direction, at

27

 

 
 

 

least in intention. However, we find that process has to date
been crippled before its final passage. Now you know by way of
background that the regulations have only produced one drug, and
to date not a single HIV-infected person has had access to any
drug under those regulations.

Dr. Young contends this is because no worthy drug has
yet been available. We believe, instead, that this is because of
flaws in the structure of that regulation.

Treatment use process has failed because the
regulation itself appears to have been deliberately emasculated
before its final passage. Now this is a fairly complex subject
here, and I think it is critical that the commission know the
actual language of the treatment IND regulation as it was passed
and the language under which it was first proposed by Dr. Young,
and there are some significant gaps between what he originally
proposed and what in fact he was able to move through the federal
system.

In the original version he proposed that a treatment
use of an experimental drug should be denied to a patient only
when the evidence, taken as a whole, showed that the drug did not
provide a therapeutic benefit, or when it was harmful.

In other words, he had relaxed the standard of
efficacy required for releasing a drug, a concept we agreed with.
This version was completely consistent with the advertised
purpose of the regulation.

In the final version of the regulation, however, that
was changed. In the current version of it, as printed in the
Congressional Record, it says that treatment use would be denied
when the scientific evidence, taken as a whole, fails to provide
a reasonable basis for finding the drug effective. In other
words, the drug must now again be shown to be effective. And if
we insist that efficacy be proven for a drug, we are back to
square one. No change has taken place.

At best, under the regulation, all that has been
eliminated is some of the ludicrous paper-pushing that normally
occurred even after a drug had been proven effective. We have
taken perhaps a year off the treatment process or the treatment
licensing process, not the many years that had been proposed.

Now you have to ask, "Why did this take place, what
happened here?" because it did seem that Dr. Young had moved in
the direction that we had wanted.

Our investigation tells us that this change came about
in response to pressure from the Pharmaceutical Manufacturers
Association, which acted to protect the interests of the largest

28

 

 
 

manufacturers, primarily against inroads by the smaller ones.
Under the current system, only the largest manufacturers can
afford to support the many millions of dollars it takes to
license a clinical drug. Under the new system, that would have
been changed and in fact Dr. Young said that was one of his
intentions in making that new regulation.

That aspect of the regulation was also opposed by the
most conservative members of the medical establishment, whose
concern as you noted the other day for risk overweighed their
concern for possible benefits.

Commissioner Young in private meetings with us
including just here yesterday while sitting in the audience
admitted that this was a failing of the regulation. But he
pleads with us for understanding on the grounds that he got what
he could within the federal system, even though it is not the
ideal that he had asked for.

I think it is critical that this Commission in private
ask Dr. Young and how you can help get what he actually asked,
how you can help him get around the objections that he had faced.

The regulation is further damaged, we feel, because the
language used to describe efficacy, once efficacy was put back
into it, that language is extremely vague and subjective, yet in
effect it leaves all power to release a drug solely in the hands
of the Commissioner. We believe that to date that power has been
wielded in a somewhat capricious manner and we can point to
examples in which that has been the case.

There are currently no accountability for how Dr. Young
interprets that efficacy standard and there are no printed
standards which he must adhere to.

Now obviously we believe that the immediate, wider
treatment use of AIDS-related therapies for drugs which are safe
and have a reasonable expectation of efficacy will benefit many
people in our community. We also feel it will speed the process
of research and make more drugs available to the community
research initiative.

As it stands now, many of the drugs which could be made
available in the manner are already in use by patients, as you
have heard. People are getting them from other countries, they
are manufacturing them on their own. However, this method of
getting them adds greatly to the cost, diminishes the
effectiveness and probably raises grave questions of safety and
adds nothing to the database of treatment information.

Now to rectify this, we suggest several specific
changes.

29

 
 

 

Number one is simply to define or remove the efficacy
requirement in the existing regulation. My preference is that we
go back to the original language that Dr. Young proposed; if
not, that we ask him to define in concrete, measurable terms what
standard of efficacy a drug must meet in order to get a treatment
IND. I don't believe that our group should be the only one to
have input on this, nor do I believe that FDA should be the only
one. I believe that pharmaceutical manufacturers, the National
Institutes of Health and the AIDS community itself should have
input on what the level of efficacy required should be.

To date, this failure or refusal to define the standard
of efficacy has led to a crippling fight over the release of one
AIDS drug: you have heard it referred to repeatedly in these
meetings as "the Ribavirin story," in which FDA has turned down
the treatment IND in direct opposition to the ATEU sponsored
investigators who studied the drug. I have supplied you with a
great deal of information on that situation and I would hope the
commission would read it.

Recommendation number two: This commission should ask
to establish a national databank for monitoring the treatment use
of new drugs.

Number three: It must to establish clear endpoints for
treatment use. We certainly don't want drugs out there that
can't be taken off the market if they are hurting people.

Number four: We need to ask for certification of
physicians for their role under treatment use, so that not
everyone in the world is out there using these drugs, but rather
physicians who are certified to use them and to supply data in a
clear and consistent manner.

Number five: We must establish legal protection for
sponsors and physicians for treatment use. We are in complete
support of the commission's expressed interest yesterday in
creating legislation to provide this protection.

Number six: We ask that you establish a National
Clearinghouse for Treatment Use Information, so that patients and
physicians be in the position to make informed consent on the use
of these drugs.

Number seven: To establish a formal link between this
treatment use process and the community research efforts you have
heard described here this morning; they are natural partners.

Number eight, and a very important point: We must
establish a mechanism under which manufacturers can be induced to
make their products available under the treatment IND. Currently

30

 

 
 

 

it is solely up to the whim of the manufacturer to do that and
that is not acceptable.

In conclusion, we want to say that FDA is on the right
track with these regulations but has shot itself in the foot with
the way the regulation was worded. I don't fault Frank Young for
that; I think he tried to do it correctly and he was forced by
forces beyond his power to change that regulation and I would ask
you to give me support to correct it.

In closing, I want to make a brief statement here about
the conflicting voices that you hear over so many of these
issues. I know we are saying one thing, FDA, NIH may be saying
another. But I want you to look at the historical record before
you decide who you listen to.

Historically, in 1981 through 1984, the gay community
activists urged the country to allocate necessary resources to
fight this problem. Those shouts fell on deaf ears for four
years while the epidemic grew out of control. Finally people are
listening to us.

In 1982 gay activists warned of problems in the blood
supply while the public health service ignored us. They have
listened now.

For the last two years we have been urging wider trials
and investigator-initiated research to deaf ears at NIH.
Yesterday you heard them urge the same thing.

And finally, since 1984 we have been telling you that
there are safe and effective remedies already in use, please
listen to us.

DR. LILLY: We have three more speakers and very little
time left now. I would hope that the other speakers can keep to
a somewhat more reasonable time frame.

The next speaker will be John James, who has for some
time been putting together a newsletter with respect to
information about drug treatments for AIDS.

MR. JAMES: Thank you for having us here and for having
such a broad range of viewpoints in these hearings. That builds
confidence.

Just one change in the schedule. The name of the
newsletter is "John James Newsletter." It has gotten called that
but that has never been its name. I don't know where it came
from. The name is "AIDS Treatment News." I think you have my
statement, so I won't read it all. But I will indicate some of
what is there and leave it for the record.

31

 

 
 

 

Anyway, this began as a volunteer effort for an AIDS
organization of Documentation of AIDS Issues and Research
Foundation in San Francisco and it just grew. It was not started
by intent. It grew to a circulation of 3500 in one year with no
advertising or promotion, just be word of mouth, indicating the
need of people for the information.

People with AIDS react in different ways. The people
I hear from are the people who do want to take a personal
involvement in their medical care. The people who resign
themselves to death or who decide that they are just going to
follow their doctors and not be involved, I don't hear from them.

But from these people I do hear it is a unique
viewpoint, being on the phone continuously -- that is how the
newsletter is put together. I am not a physician, I am not a
scientist. I am doing this as a journalist, talking to people,
getting on computer databases, talking to scientists and
physicians to persons with AIDS and ARC.

One of the comments -- thoughts in trying to bring
this together was that oddly enough, there doesn't seem to have
been a survey -- I don't know of a survey of people with AIDS or
ARC or antibody positive asymptomatic people, as to what they
think is a scientifically, professionally conducted survey as to
what they see as going on, what they would like to see as changes
in the process.

In fact one of my recommendations in this paper is that
such studies be conducted. In the absence of that I took as
putting together a wish list -- actually we're just one item on
the wish list from Dr. Nathaniel Pier, who is a physician in New
York in private practice with a caseload of about 300 people with
AIDS or related conditions.

He commented that above all that anybody diagnosed said
for the wish list of what he believes we should have, which I
believe is as close as anything I have hear to what the AIDS
community I am in touch with wants. Anybody diagnosed with
HIV-related disease or immunodeficiency be given a full
assessment of their situation and be allowed to choose to receive
a therapeutic regimen or decline it.

Theoretically all 500,000 persons infected in New York
should be allowed access to some form of therapy if they wished.

To satisfy scientific needs they could be enrolled in
formal protocols. Otherwise clinicians should be allowed to use
empirical regimens with patients properly monitored. This way
everyone would be given the optimal chance to save their lives
and nobody would be allowed to twist in the wind. Furthermore,

32

 

 
 

 

‘3 Sse vt

we could look at the results and get a sense of what works much
more rapidly than under the current systen.

Persons could use single drug treatments or rational
combinations based on the best judgment of experienced
physicians. What is happening now is that it takes several years
of preliminaries on single drugs before combinations have been
approved and yet most of the experts have believed for years that
combinations are going to be required.

What we propose here is what is already done -- this is
Dr. Pier again -- with cancer patients. Almost no one diagnosed
in the United States today with cancer is denied an opportunity
to participate in potentially life-saving therapy. There is in
place a widely-accepted system for providing these experimental
and established therapies to cancer patients. This system
advances our knowledge of the treatments for this disease, but is
also a humane and compassionate way of caring for patients.

To the argument that there are no AIDS treatments
except AZT because no others have been proven effective, we would
answer that we are currently capable of choosing safe, rational
approaches to therapies. In addition, people. are using these
therapies anyway. Our proposal would allow them to do so under
Supervision so this can be done safety and the data developed can
be critically evaluated and thereby be helpful to others instead
of remaining anecdotal.

Okay, the next section on problems I will have to skim
that and get on to recommendations, but there are a lot of
details in here, there are some things in here in fact that have
never been public before and I recommend that investigators for
the commission take a look at the written material.

Just to briefly -- Dr. Pier worked for about two years
trying to get some consideration of the drug called Lentinan,
which I understand has currently been placed in the highest
priority at NIH, but he worked two years completely fruitlessly
on it. He was surprised by the current interest and it is my
understanding from him that, talking to one of the people on the
community, there wasn't any new information. It was just a
hunch. In other words, the decision could have been made four
years ago when the first indications in Japanese research -- this
drug is used in cancer treatment in Japan -- and it was reported
that .it was effective in treating retroviral infection to
patients, HIV and HTLV-1.

Anyway, there is a pack of correspondence which is
submitted into the. record with this and that can be reviewed.
That is his correspondence with federal agencies and others in
attempting to get some consideration and his effort was entirely
fruitless until possibly today.

33

 

 
 

 

Some other concerns besides that one, we have heard - -
this is one of the pieces of new information on AL-721, a comment
of the unhappy story of repeated failures are described at length
in the back issues of my newsletter which have been put in a
15-page computer generated index and they have been entered into
the record also. So there is a copy of this. That you can
follow historically. The old articles have not been changed
except for update sections, so you can just see historically as
it has been covered over the last year and a half, what's
happened.

We have also heard reliable information that AL-721 was
used to treat one person successfully before it was even brought
to Dr. Robert Gallo's attention in the laboratory test. My
understanding is that Dr. Gallo did not know that, however some
of the people involved in promoting the drug believed in it
because of the results in an actual case. This has never been
public before. Part of the investigation by the way, there is
somebody writing a book on AL-721 and I can get you in touch with
him. His number is in the back issues here also.

One of the commissioners yesterday asked Dr. Frank
Young of the FDA what about the possibility of medical treatment
to help with the drug abuse problem. AL-721 was originally
developed and is still a promising candidate as something to help
relieve withdrawal symptoms and therefore help people get off of
the drugs permanently. However we have not had even a little
pilot test with 10 or 20 people to see if this approach merits
further investigation. It has been known for years, it's been
known from animal, from laboratory, from theoretical
considerations only -- not even a small test on people.

Trimetrexate is another concern. That is the one that
was just released in the treatment IND, which of course we are
very happy to see. But there is theoretical reason to believe,
and physicians who are knowledgeable are quite interested in
Trimetrexate as a possible use for cryptosporidiosis also. There
is no satisfactory treatment for that; that is the one that
causes a severe and often fatal diarrhea in people with AIDS. It
looks like this would work. It is so safe that almost nobody had
to be taken off the treatment of people with AIDS for
pneumocystis. However, I learned yesterday in talking with one
of the company spokespeople that the manufacturer has no intent
of developing it for any other opportunistic infection than
pneumocystis for AIDS and I have been hearing that physicians
have been unable to receive it under compassionate use for
cryptosporidiosis. So in other words in the current system, it
will never be tested.

The Salk polio vaccine -- this is not the new Salk
vaccine that is being worked on, this is the old one from the
'S0s -- several physicians have used this in treatment of

34

 

 
 

 

persons with ARC especially and are quite enthusiastic. They
don't say that it works, but it ought to be tried. Recently
physicians have had a hard time purchasing the vaccine from the
only company in the United States authorized to supply it. They
have been getting things like, "You have to sign an affidavit
that you will use this only for immunization against polio."

Now this is a drug that is regularly available.
Physicians have every right to use it for use other than the
approved use and I don't know how this is going to resolve itself
but I have heard from two different groups of people that they
have had trouble with the company buying this regime.

DR. LILLY: I am sorry to interrupt you but I am afraid
we are going to run out of time and you said in your write-up you
have 10 recommendations coming up. It is that we would like
really most to hear.

MR. JAMES: Right. I'11 skip to the recommendations.

DR. LILLY: I'll skip to the recommendations as to what
we can do to help out. Much of what we are talking about we have
here before.

MR. JAMES: Okay, recommendations:

1. The Commission or another body investigate the
problems cited above.

2. The Commission arrange for a survey of people with
AIDS or ARC as to what they see going on, what they would like to
have happen.

3. The Commission ask the FDA to provide guidelines to
researchers outlining what studies would be required to qualify a
drug for a treatment IND. You have heard that. And it should
also say when it is or is not ethical to require a placebo and
when it is or is not ethical to withhold proven therapies such as
pneumocystis prophylaxis. The problem is that we are concerned
that some of these requirements are being placed on the studies
under the table. We want the FDA to put its name on exactly what
the ethics requirements are. We are concerned that studies -- a
placebo is required when it shouldn't be and the pneumocystic
prophylaxis and other important treatments are withheld.

4. The Commission recommend creation of a public
computerized and printed registry of all human trials and should
include from each one, each drug the protocols and language that
can be understood by a lay person -- required for federally
funded programs and encouraged for private ones -- and take steps
to make access equally available to all qualified persons.

35

 

 
 

5. A system must be established for ensuring fair
access to everyone in need, such as a lottery. If you look it
has been almost entirely white and often gay people in the
protocols so far and male very often.

6. That the commission suggest the creation of a
confidential, voluntary registry of individuals affected whereby
they be informed of trials for which they qualify. That would
also help in the recruiting which scientists say they have a
problem with, but if everybody who wishes to register is told the
people that want to get into these trials.

7. The commission recommend the immediate expansion of
funding for experimental trials organized and run at the
community level, such as CRI.

8. Encourage the current attempts to share are
disseminate reagents, materials and scientific data within the
scientific community. NIH has done some programs on this that
make it possible for researchers to obtain good monoclonal
antibodies and such cell lines and such.

9. That the Commission recommend the development of a
system such as compulsory licensing, which would prevent
proprietary restrictions on data and access to drugs from
impeding development of AIDS treatment.

10. We urge the Commission to recommend that
individual patients and their physicians be allowed to choose
safe experimental therapies under supervision even before
efficacy has been confirmed if informed consent is obtained.

And the rest of it is in the record.

[The prepared statement of Mr. James is included in
the Appendix. J

DR. LILLY: Thank you very much. Our next speaker is
Mr. John Scafuti representing a buyers' club in Orlando, Florida,
as well as Home Health Care Services, AID Orlando, the University
of Central Florida Task Force on AIDS, and Orlando Gay Community
Services.

MR. SCAFUTI: Dr. Lilly, Admiral Watkins and
distinguished members of the Commission, thank you for allowing
me this opportunity to offer proposals to defeat this epidemic.

While it is a little difficult for someone from the
South to talk rapidly, I will do my best in the interest of time.

(Laughter. ]

36

 

 
 

 

DR. LILLY: Thank you.

MR. SCAFUTI: My testimony is dedicated to the memories
of three particularly motivated men who have preceded me here,
Tom Jefferson, Patrick Haney and Jim Sammone. They have all
expired within the last two months, highlighting the urgency of
our task.

I will present two sets of recommendations for
expediting delivery of unauthorized or investigational new drugs
at the earliest possible time. The first set of suggestions are
made within the current framework of the drug approval system. I
estimate this method of proceeding to be only half as effective
as the second more comprehensive set.

Under the new regulations governing IND compassionate
use treatments and IND protocols, a specific example is cited on
page 19467, column two, next to the last paragraph, qualifying
all stages of HIV infection as "immediately life-threatened,"
thereby clearing the way for even the asymptomatic patients to
receive the most advanced treatments as soon as possible.

With as many as two million potential clinical
subjects, there should be no problems filling clinical trials, a
requirement for consideration of IND compassionate use
treatments.

In most of the current trials in progress clinical
subjects are recruited from the most financially secure and most
pharmaceutically sophisticated patients. Both the FDA and the
pharmaceutical companies fail to address the implications of this
reality.

These patients are much more likely to follow through
with the full term of the trial but are not nearly as likely to
adhere to the conditions of the trial. This results in a smaller
subject population but questionable validity.

A far more fertile source of clinical subjects is in
the very clinics where current care is significantly inferior, VA
hospitals, prisons and free government clinics. This would offer
some hope of advanced treatments to the underprivileged that
doesn't now exist.

While the populations in the trials would have to be
expanded to allow for a higher dropout, the trials would be far
more valid due to closer adherence to the testing conditions.
There will be charges of bias against the underprivileged and of
using them as guinea pigs.

The truth is that their care will be significantly
improved, they will enjoy a sense of contribution to society and

37

 

 
 

 

the financial burden for much of their care will be shifted to
the private sector, the pharmaceutical companies. The test
results would be far more valid due to closer adherence to the
conditions of the trial. In short, the positives far outweigh
the negatives, regardless of the potential criticism.

Under the new FDA regulations for IND compassionate use
treatment protocols, a surprising possibility has emerged. By
the time a drug has neared the end of Phase II, small controlled
studies, and the four general criteria have been met allowing IND
treatments to begin, there may be more liability to the
physician, pharmaceutical company and the FDA for not providing
the drug than that which is associated with providing it.

An interesting historical fact is that only one case
has been tried where an investigational new drug was
administered. The decision in all of the courts was consistently
for the defendants. What this indicates is that early usage of
promising new drugs for AIDS is likely to be rather non-
litigious, while delaying usage, conversely, could attract
significant class-action litigation.

Two major defects in the IND treatment approach could
and probably will nix the whole system. While the FDA seems to
be bending over backwards to provide promising drugs at the
earliest possible time, the pharmaceutical companies are not
compelled to provide the drugs and the third party payers,
Medicare, Medicaid and private insurance, are not compelled to
pay for the drugs.

Historically, the FDA has played a passive role. Even
if they are now inclined to be more proactive, it will be some
time before they will be capable of making that adjustment.

To make the system work, the government must put the
public interests of the ravaged populations above the proprietary
interests of the pharmaceutical companies. The appropriate
legislation accomplishing this must be enacted.

Part of that same legislation should include a
requirement that third party payers must pay for all IND
treatment situations. Without this legislation, the new FDA
regulations are clearly worthless with only the very wealthy
having any opportunity to use expensive investigational new drugs
such as Ampligen.

The next set of recommendations fall outside of the
current health care and drug approval systems. Do not pursue a
Manhattan Project for AIDS. The historical Manhattan Project had
a narrow well-defined purpose. The scope and implications of
this disease are far too broad and comprehensive to be dealt with
in the same manner.

38

 

 
 

 

Such a project would likely be biased towards strictly
HIV theory, be focused on magic bullets rather than disease
control, and would not adequately address multifactorial
possibilities.

. Instead of the Manhattan Project, the Congress or the
President should literally "Declare War on AIDS" and appoint
"Joint Chiefs of Staff" under the Department of Health. This
body should have the same power to fight AIDS as its military
counterpart during times of war.

Represented on this committee should be the Surgeon
General, the Commissioner of the FDA, the head of the NIH, the
Commissioner of Insurance, a representative of the pharmaceutical
industry and the head of the Department of HRS.

Balancing the traditional government and bureaucratic
bias in the composition just stated, it is essential that leaders
of groups hardest hit by this epidemic be well represented on
this panel: homosexuals, blacks, hemophiliacs and women.

Since many of the anticipated decisions will be
economic and based upon questionable statistical data, it is
essential to include cost accountants and statisticians as well.
At no time should the private representation be outnumbered by
the government representation.

A significant effort should be made to include HIV
positive individuals whenever possible. No one has a greater
inherent human right to make decisions affecting survival than
those who are struggling personally to survive. This would
formulate strategy, implement policies and serve as a board of
appeal for conflicts which would inevitably arise.

Rather than trying to squelch the AIDS drug
underground, those efforts would be miserably unsuccessful, ill-
advised and a huge waste of time, money and energy. We should
instead devise a strategy for gaining as much information as
possible from that system. We must provide physicians with
incentives to track and report the polypharmaceutical treatment
strategies which are being followed by their patients.

Most experts agree that ultimately a multifactorial
approach consisting of combinations of anti-virals, immune
enhancers and immune modulators will effect the greatest degree
of disease control.

Instead of fighting what is going to occur anyway, we
could gain valuable insights for controlled combinational
studies based upon subjective indications which become apparent
when the data is reported in huge numbers by physicians
throughout the country.

39

 

 
 

 

To create incentives for this project, I propose the
following:

--Number one, statisticians working with highly
informed physicians and researchers who have an understanding of
the polypharmaceutical possibilities would design computerized
patient histories, regimens, baseline and maintenance lab data in
the most convenient fashion possible.

--Number two, participating physicians should be given
a prestigious labeling which could be recognized by the general
public in advertising media, for example, NDI - "New Drug
Investigator."

--Number three, provide participating physicians with
the most sophisticated interactive data retrieval system to date,
enabling them to know immediately as evolutionary advances in
treatment possibilities are occurring. Also include a complete
registry of all trials planned or in progress relative to any
AIDS issue.

--Number four, the government should pay the physician
for his additional efforts on a per patient basis.

The significance of creating the model described above
cannot be underestimated. While there are very few reports of
drug interactions with AIDS, there is no responsible tracking
going on and extremely useful combinations may be going
unnoticed.

By expanding the subject population to enormous
proportions we can validly include a large number of variables
and still produce extremely valuable subjective indications for
more controlled research. This offers the opportunity of "leap
frogging" current step-by-step traditional research.

Another area of concern that heretofore has gone
unaddressed is the degree of infectiousness by those that are
pursuing aggressive anti-viral regimes and are consistently
antigen negative and consistently viral culture negative.
Virtually all other retroviruses go into relative infectious
remission and yet remain in the body.

We cannot let these epidemiological possibilities go
unexplored. I do not suggest that behavioral changes be
abandoned, quite the contrary but we must not ignore any
possibilities for epidemiological control. There is no research
that I am aware of that explores this issue. We are told that
saliva does not transmit AIDS because viral concentrations are
too low to accomplish infection. It is notable that we are not
told that there is no virus in saliva. What about other areas of
drug-induced low viral concentrations?

40

 

 
 

 

These proposals are.obviously not "business as usual."
Imagine the progress we could make if they are implemented. It
is long past time to drop a "business as usual" approach.
Several enclosures have been included which support the
conclusions reached above.

Enclosure number one is a lengthy example of a child
thriving by using unauthorized drugs. Enclosure number two is an
example if inferior medical care which exists in VA hospitals and
enclosure number three is an example of results using drugs prior
to marketing approval, DHPG.

Thank you very much for your consideration.
[Applause. ]

[The prepared statement of Mr. Scafuti is included in
the Appendix. ]

DR. LILLY: Thank you, Mr. Scafuti. I would like
rapidly to go on to finish this segment with a presentation from
Dr. Herb Spires who represents the organization ACT UP here in
New York.

DR. SPIERS: Mr. Chairman and distinguished members of
the President's Commission on AIDS. Thank you for the
opportunity of presenting the testimony on behalf of ACT UP, the
AIDS Coalition to Unleash Power.

In the race against time, I will read like the hare if
you promise me that you will listen not like the tortoise. For
us, AIDS is not only about health, it is about politics. This is
a connection many of you may find difficult to accept. I first
became aware of AIDS in the summer of 1981 when it was called
"gay cancer."

I now realize that I made a fatal error in my
understanding then. I focused on the word "cancer" and assumed
that this new and mysterious disease would be dealt with in the
Same manner as Legionnaire's Disease, which is to say with great
urgency from our medical establishments and the White House
alike. It was not.

It was a politically unpopular illness and not until a
few courageous voices spoke out against the lackadaisical
political and medical response to the by then already epidemic
proportion of the disease did the true personal, social and
cultural horror begin to stir the national conscience.

This historical context is the framework by which we
judge today's promises of fast-tracked drug developments and
redesigned systems for clinical trials.

41

 

 
 

 

It is from within this tradition of neglect, even
though perhaps benign neglect, that we are compelled to make
sense of the fact that as of this moment a person with AIDS has,
in the entire breadth of this nation, access to only one ATEU
trial testing a drug other than AZT and at that, there are only
25 slots available.

This historical context prompts us to ask embarrassing
and provocative questions. Is scientific methodology really the
only reason that as of February 5, 1988 83, percent of all people
enrolled in ATEU trials are on AZT? Are our scientific wits so
dull that we cannot find effective alternatives to cruel and
self-defeating double-blind placebo trials? Are women, Blacks,
children, Hispanics and drug users somehow innately unqualified
for drug trials for they are woefully under represented in trials
currently underway?

Is the NIH really committed to a worldwide search for
potential new drugs or is it too comfortably wedded to domestic
products? Why must drug companies retest potentially life-
saving drugs because the FDA fails to make its rules and
regulations for the design of acceptable protocols clear and
comprehensible?

In making answer to these and other questions the
politics of drug development must be addressed. There is still a
leadership vacuum in the fight against AIDS. Despite the noble
intentions of political and bureaucratic functionaries, AIDS will
remain a controversial issue on the national agenda until the
Chief Executive of our country removes it from partisan and
ideological politics by personal moral examples and by bold
leadership.

We have been told that AIDS is the nation's number one
health problem, yet this four letter word was not once uttered in
President Reagan's State of the Union address last January.

Is this the type of example to set for his
subordinates? Does this demonstrate commitment and concern? Can
the President not hold publicly an AIDS baby in his arms or avail
himself of a photo opportunity to shake hands with a Person with
AIDS to educate the public about compassion and how this disease
is really transmitted? Let's start at the top. Let's start with
the role of the Chief Executive. Recommend to this President and
the next to become truly involved in the fight against AIDS.

You know that the AIDS Treatment and Evaluation Program
has not been a resounding success. After 18 months not a single
report has been published. You have been told that it has been
revamped and redesigned, that new committees have been added to
expedite the testing of more and different drugs.

42

 

 
 

 

Nothing could please us more than to see that happen.
But we have had experience with the ATEU program first hand and
we know that if it is going to work it must, one, include
participation from community physicians and, two, must win the
confidence of the very people it seeks to recruit.

This means outreach to AIDS communities in culturally
appropriate ways such as designing clinical trials commensurate
with nonwhite, non-middle class values. It means alternatives to .
placebo trials and it means convincing people like Dr. Iris Long
sitting to my immediate right that genuine efforts are being
made.

ACT UP is singularly proud of Dr. Long. There is
perhaps no more informed person on drug treatments currently
underway in this country than she. What we have learned about
the problems with the ATEU program can be of use in preventing
similar errors in the new program.

Not content with simply a critic's role, Dr. Long and
several other ACT UP people have undertaken a pilot project that
will serve as a prototype for a national effort. We are
developing our own data bank on treatments at hospitals in the
greater New York area.

Physicians and PWAs need up-to-date information about
drugs and drug treatments and this information is nowhere
available. Certainly, the government's databases, PDQ and
CLINPROT are not the answer. In addition, ACT UP will
demonstrate the importance of a Central Registry of clinical
trials for researchers and physicians, another idea we strongly
urge this committee to take under advisement.

For many of us, perhaps for many of you as well, there
is still a mystery as to how drugs are selected for clinical
trials by the NIH. Successes or failures notwithstanding, it has
never been satisfactorily explained why AZT and not some other
drug or drugs was put on a fast track approval process by the NIH
and the FDA.

Recent press reports once again testify to the
inherent suspicion on the part of our great medical
establishments to substances developed abroad. To ensure that
domestic business considerations should never be allowed to
impinge upon drug selections we urge the creation of an
Ombudsagency to examine the experience of other countries in the
search for new drugs to be tested.

"The real problem," says Commissioner Young, “is where
do you get the ideas and where do you get the compounds from?
That is the major block." Mandate imagination and creative
research through such an Ombudsagency.

43

 

 
 

 

To de-mystify the process of drug selection and to
inspire trust and confidence within the various AIDS communities
we make two recommendations. First, both the FDA and the NIH
must make greater efforts in providing timely and current
information that is organized and systematized. The above
mentioned national database is indispensable in this regard as
are monthly and weekly publications and a National Hotline on
drugs and treatments to which physicians and PWAs can make
reference. Second, structure community physicians' and PWAs'
participation in all drug review committees.

On Tuesday of this week with not a little fanfare, the
FDA announced that trimetrexate had been approved under a
Treatment IND. Bravo! But questions remain as to liability and
treatment costs within a Treatment IND protocol and in spite of a
two day conference just this week, the regulations pertaining to
Treatment INDs remain murky, prompting a number of informed
persons to wonder whether pharmaceutical companies would indeed
submit their drugs for Treatment IND approval.

You have heard some glowing reports from the FDA
Commissioner. Let's hope they come to fruition. But again we
have historical reasons for being more than a little skeptical.
Supposedly thousands of drugs have been examined, over 40 are
"in-the-works" yet only AZT is approved.

What is the status of DHPG, the only hope for people
suffering from CMV infection? Will or will not the Commissioner
approve its release or must the parent company put it back into
trials causing further delay of the only drug effective against
CMV retinitis?

And who in the government is willing to take even a
modicum of responsibility for possible abuse of The Orphan Drug
Act? The government grants exclusion drug marketing rights to
companies, yet it refuses to monitor possible abuses of a
federally created monopoly.

In 1984, Pentamidine cost $24.95 a vial. It now costs
four times that amount. Who pays for this whopping increase?
Individuals, insurers and in a variety of ways, taxpayers.

While the government granted a marketing monopoly to
Lyphomed for Pentamidine, the FDA's Office of Orphan Products
Development says that it has no monitoring power. We all know
too well the astronomical cost of AZT, another Orphan Drug Act
product.

This act was intended to induce companies to develop
drugs that otherwise would go undeveloped without forms of

44

 

 
 

 

financial assistance. A wise policy and within the tradition of
Chrysler and Lockheed bailouts.

But has it become a government handout? Perhaps it is
time to consider a Untied States Drug Development Corporation
that would be self-financing and would treat drug patents and
marketing rights as part of the public commonwealth.

Time does not permit me to focus attention on other
issues with which we are concerned. For example, does the FDA's
Informed Consent Regulation, 21 CFR 50, which requires informing
patients of alternative therapies before signing them up for a
trial mean making them conversant with drugs and treatments being
used in a limited geographical area or does it mean all drugs and
treatments used throughout the country?

Obviously, the answer to this question is of
significant moral and legal importance. Discrimination, housing
and health care, education are all part of the politics of AIDS.

The National Leadership Coalition Against AIDS, a group
of business leaders, recently suggested a bill of rights for
Persons with AIDS and for seropositives. Its time has certainly
come and I commend their idea to you.

I wish to close with that with which I began. We the
women and men of ACT UP are gadflies, the grassroots variety.
That is why this Commission, the White House, Dr. Young at the
FDA, Dr. Fauci at the NIH, governors, mayors, representatives,
council members, senators, health commissioners, candidates and
many other varieties of politicians and bureaucrats and their
anointed appointees, find us buzzing about.

We are driven by the Politics of AIDS and despite
attempts to shoo us aside, to ignore us, spray us with
insecticide, and all other means to dispel unwanted pests, or
more accurately, those perceived to be pests, we will in the
tradition of political gadflies keep you honest by "ACTing UP."

(Applause. ]

DR. SPIERS: Recent rhetoric would have us believe that
the epidemic is over, at least here in the U.S. It isa
consummation devoutly to be wished. Still, one cannot help but
wonder if the very same people who were so late in coming to the
battle are not prematurely calling it at an end?

For many here present this morning, the full effect of
the politics of AIDS was brought home forcefully by the death in
one's arms of a lover or a son or the diagnosis of Kaposi's
sarcoma in oneself or in a friend.

45

 

 
 

 

My mistake, the mistake of those most effected by this
disease, was to remain silent too long; quiet in the assumption
that the health of the body politic was above the ideological
issues of partisan politics.

With our mouths closed we watched the deaths mount. In
high school, we were taught that the price of freedom is eternal
vigilance. Sad to say, in the Age of AIDS, many of us have
learned that in our democratic society the price of health is
perpetual pressure and an ever ready pair of vocal cords.

In fighting for the cause of human life, no price is
too high. And so, even though some contend that the epidemic is
over because they believe it has not entered the white
middle-class, heterosexual population, we will continue to bring
pressure to bear commensurate with the goal we are seeking, an
end to AIDS, an end to dying.

My testimony, then, is a kind of pressure, delivered
before you in the form of verbal pleading. We ask you to examine
fairly, carefully, critically all the testimony that you have
heard and received. Weigh it on the scale of scientific merit
and reason, but also measure it with the rule of your own
personal integrity. You will be making recommendations affecting
who will or will not suffer, who will or will not die.

On this issue, we cannot and will not ever be silent
again. We ask that your officially sanctioned voices speak out
with us. Thank you.

[Applause. ]

(The prepared statement of Mr. Spires is included in
the Appendix. ]

DR. LILLY: Thank you, Dr. Spiers. The length of the
presentations precluded us from asking questions. Those members
of the Commission who have questions to ask you will submit them
to you in writing and I would be appreciative if you would
respond to them as rapidly as possible.

MR. DELANEY: Dr. Lilly, let me say that I resent the
fact that our community members have been forced to squeeze their
presentations and are limited in time here. Three PWAs yesterday
were given seven minutes each to speak. Dr. Young got two and a
half hours.

DR. LILLY: I am sensitive to that. I think, however,
that we have understood your points of view and I will certainly
do everything in my power to see that the Commission pays
attention to your points of view.

46

 

 
 

 

HIV Infection in Women

DR. LILLY: The next panel will consist of two
presentations concerning HIV infection in women, an issue that
the previous panel has stressed as being of considerable
importance.

Our panel on HIV infection in women is represented by
two individuals, Denise Ribble, a nurse educator at the Community
Health Project will be our first speaker.

. MS. RIBBLE: Good morning, members of the Commission,
the three of you that are still there.

In the context of women and AIDS, transmission studies
have established that men can infect women sexually, that female
IV drug users can get AIDS, that women can infect men sexually to
a much lesser degree and that infected mothers can pass this on
to their babies.

However, transmission studies do little for the woman
who has been an epidemiological guinea pig. Though researchers
often glean a very complete medical, social, sexual and drug
history from these women, they do not provide risk reduction
education. They do not provide support in dealing with
transmission dynamics.

Transmission dynamics is a polite way to describe a
situation when a woman in a culture that doesn't talk about sex
would like to practice safer sex with a man who doesn't want to
put on a condom.

Transmission studies do not provide information on what
kinds of care and services infected women need. In New York
City, in fact, infected mothers are enrolled in studies and once
they have their babies, their babies are enrolled in follow-up
medical studies and the women are not enrolled in any kind of
follow-up medical or psychosocial study.

No one cares about prostitutes as infected women,
however, there is considerable interest in their role as a
vectors of disease, forcing those men to have sex with them, no
doubt.

[Applause. J
MS. RIBBLE: The reality in my experience is that men

pay 15-year old girls a premium price to have sex without a
condom.

47

 

 
 

 

There has been a disturbing trend recently to minimize
the risk to heterosexual women based on transmission to the
general population and I just kind of want to review kid of what
two percent or 2.6 percent transmission in the general population
means. In New York City what that means is that if there are a
million women who are living in New York and 2.6 percent are
infected, then there are 26,000 infected women living in New York
City right now.

These are not women who are at high risk because we
know the transmission rates in women who are at high risk are
much higher than 2.6 percent. These are women who decide that
they will participate in a transmission study.

The fact is that women are at risk, okay, and the fact
that they are not necessarily perceived at risk and, then, not in
need of services continues to be a problem in everything from
public health education to research protocols.

For women at risk or infected this perception is
another obstacle in access to medical care and psychosocial
Support. Where is the research into prevention for risk
reduction strategies for women and the resources to reach them as
individuals in families and in their diverse communities?

There are 4,100 cases of CDC documented AIDS in women.
There has been a statement made that these women are sicker and
die faster. Eight years into the epidemic, we don't know why.
Where is the research into saving women's lives?

There are no co-factor studies right now that
specifically address co-factor issues in women. There is a
study that is starting in New York City at Columbia University.
When I called Columbia to ask to enroll some of my female
clients in their study they told me that they could be enrolled
through a methadone maintenance program.

However, most of my clients are not, nor have they ever
been, IV drug users. There are also a few lesbians in my female
clientele population and for them to go to a methadone
maintenance center to participate in a transmission co-factor
study is kind of ridiculous.

I was informed that the questionnaire that would
address those women, the ones in my clinic, was being worked on
right now and would probably be piloted three or four months from
now.

Studies have shown that ethnicity is a high risk but
there are no studies that discuss ethnicity and/or being female.
Researchers have suggested that the disease may have a different
etiology in women and they suggest further study but they do

48

 
 

 

little to actively recruit women into those studies. When asked
why, they make statements like "women are a harder population to
study. They are unreliable. They are not homogeneous." Yes,
indeed. You are right. They are not.

(Applause. ]

MS. RIBBLE: Other possible co-factors that might
contribute to the disease in women include things like female
hormones, other infectious agents, genetics, psychological
state, ethnicity, chemical dependency, health related activities,
support networks and stress. Since there are no studies we don't
know the role these co-factors play and what others might be
involved.

Co-factor studies should include women and while we are
at it, let's not just study women for five years, let's plan for
co-factor interventions and study for improving the odds of their
survival.

There are no studies of the efficacy of alternative
treatments for women. This is compounded by the fact that there
are almost no studies of alternative treatments at all.

Current testing protocols for experimental drugs in
clinical trials exclude women in a discriminatory way. For
example, one of the inclusion criteria for the Ampligen study is
to be a gay and bisexual man. A woman can meet all of the
medical criteria but she doesn't have the biological
requirements to get into the study.

Other studies which specifically exclude women are
Isoprinosine, Immunthiol and Thymopentine. Many justifications
are given for this but the bottom line is that the FDA will
approve a drug that has never been tested in women and, in fact,
they recommend that no drugs be tested on women of child bearing
age unless it is a life threatening illness. I think AIDS is a
life threatening illness.

(Applause. ]

MS. RIBBLE: Experimental drug protocols are sometimes
made available to people who are very ill. There are even fewer
formal protocols available for people who are infected but not
severely symptomatic or immunosuppressed.

Only one experimental AIDS treatment drug has been
released for compassionate use. Most of these drugs are not
released for compassionate use and one of the reasons often given
is that the drug has not been tested in women.

49

 
 

 

This places women in the position of a double bind;
they cannot receive experimental drugs because they are excluded
from drug trials, and, they cannot receive drugs that are not
released for compassionate use because the drugs have not been
tested on women.

Women must have equal access to experimental drugs and
this must be mandated in all protocols. When dealing with a life
threatening illness, it is unacceptable to disenfranchise women.

The only other option available to women who are
infected but not sick are alternative therapies. There are
really no good studies of alternative therapies; so there is no
way to know if they are going to be effective in women; because
there is no way to know if they are going to be effective at all;
because they have not been studied.

A lot of times women do not have access to alternative
therapy information because their traditional practitioners do
not inform them that these things are available. If you are
living on welfare and you have food stamps and it costs $25.00
per month to buy vitamin C to just take 1500 milligrams a day,
there is a good chance that you cannot afford $125.00 every three
months to buy AL-721 and there is a real good chance that unless
you live on the East Coast or the West Coast, that some drugs
just won't be available to you at all.

I will to now turn the microphone over to Dr. Davis who
is going to be more specific about the needs of women and
especially minority women.

(Applause. ]

DR. LILLY: Yes, the next speaker will be Dr. Iris
Davis who is the AIDS Assessment Coordinator of the Bushwick
Medical Clinic in Brooklyn and with her is Dr. Aliyah Morgan who
is the Medical Director of this clinic. Dr. Davis will speak.

DR. DAVIS: Good morning to all members of the
Commission and audience. We are here today, Dr. Morgan and
myself, to present and highlight issues of HIV related disease
including the full blown syndrome of AIDS in women especially
dealing with women of color, those of African and Latino
derivation.

It is a difficult topic to begin with, the issue of
women with HIV disease because it is an ill-defined population
not fully stratified and without question not well studied.

The difficulties exist due to lack of definition of
health status of Black and Hispanic women in general in this
country. However, extrapolating from prior evidence and

50

 

 
 

 

knowledge that we have of morbidity and mortality, the numerous
indicators from cardiovascular disease to the rates of cancer
within these subgroups, the statistics are supportive of a
decreased health status of those communities in general as per
prior federal reports.

If we continue to look at data for women with a history
of intravenous drug use, we are struck by even higher morbidity
and mortality rates. Due to a lack of seroprevalence data, |
there are marked limitations of discussion of eventual cases of
women in all of the defined risk groups whether it be intravenous
drug use, sexual transmission or "other," including blood
transfusion.

Indeed, because present percentages are based on a
subset population of the total at-risk population and an
examination of other medical co-factors that have been linked to
the rising number of cases of AIDS in minority communities such
as tuberculosis, pelvic inflammatory disease, the increased
incidence of endocarditis, et cetera, we feel that we have
defined as a nation and certainly as a city the tip of an iceberg
alone.

The medical model of study and research is an'excellent
one perhaps for a definition of vector. However, for definition
of vector relations of sex and race and causative co-factors, it
does not help us decide how to change behavior patterns, how to
mobilize and educate communities or how to support those within
the community that are ill as cited per Friedland, et al.

When speaking of studying women with HIV disease,
especially Black and Hispanic, one must remember that they do not
present as primary patients to academic centers and their
emergency rooms. Those academic centers, however, are the ones
that determine research initiatives, support them and frequently
define the governmental response to health and disease in this
country.

Therefore, issues of clinical care, who cares for the
population at risk and who ultimately defines the access to care
both quantitatively and qualitatively may have a critical impact
on who survives or has a lower morbidity with HIV disease.

What is interesting to note in both Weston and
Rothenburg's data is that Blacks have a decreased survival time
versus whites of eight months after initial diagnosis of CDC
defined AIDS versus 18 to 24 months. In Rothenburg's
multi-varied analysis which I do not believe as yet has been
published, even when initial diagnosis, date of diagnosis, risk
group and sex are controlled, Blacks and Hispanics with AIDS
still survive for shortened periods. The reasons are still
unknown. They have not been looked at.

51

 

 
 

 

The epidemiology of HIV disease is defined by cases of
cbc defined AIDS. This continues to change in New York as the
proportion of AIDS cases after 1985 continues to increase in
Blacks and Hispanics. Women in New York City represented 11
percent of the total cases in New York City and they represent
almost half of the female cases in the nation. As of 1986 per
one hundred thousand women when we look at New York City in the
25 to 44 year old age group, there is an incidence rate of 55 per
hundred thousand for Blacks, 42 for Hispanic and ten for whites.

Eighty-four percent of all female cases are Black and
Hispanic. Only 6l-percent of those cases, however, are women who
have a known history of intravenous drug use at some point in
their recent medical history. Twenty-two percent are actually
due to sexual transmission. What is very important to note about
the mean age of the group is that it is in the early 30's, prime
child bearing years.

When we begin to examine characteristics of the male
partners which I do not think has been sufficiently discussed in
the media or in medical journals, we note that 37 percent of
males in the Black community and 23 percent of males in the
Hispanic community are bisexual. Another interesting point from
ARTC data which is data from an intravenous drug treatment
program located here in Brooklyn, that intravenous drug using
males usually tend to have non intravenous drug using partners.
These are all critical issues.

When you couple the issues together of possibly
increased incidence of bisexuality versus homosexuality within
the minority communities, as well as the fact that intravenous
drug users tend to have non-intravenous drug using partners, the
overall seroprevalence within the community might be frightfully
high and the cumulative indices, I think, give us some indication
of this.

For example, non intravenous drug using gay and
bisexual Black males have a 1.6 percent times higher incidence of
eventually developing AIDS if they are HIV positive. It is eight
times greater for Black women, 6.8 percent times greater for
Hispanic women to go from HIV positive to AIDS versus the White
population.

It is important to look at those co-factors and
determine why they exist across the spectrum for both males and
females but especially for women at such higher rates. It is
important we feel also to look at the data within New York City
as a pattern that is beginning to change not only here but is
beginning to change nationwide.

There are an increasing number of cases in San
Francisco, Houston, wherever I have had verbal communication with

52

 

 
 

 

practicing associates like myself who are community based across
the nation and practice in minority and urban communities.

New York City has 30-percent of the total cases in the
nation. Now 16-percent of all cases in the nation are in the
municipal system of the New York City Health and Hospitals
Corporation.

Therefore, it becomes extremely important to look at
preconceptions based on misleading data. Statistics do not
reveal the distinction between those individuals who have had
intravenous drug use ten times in their life or every day, 15
times a day. They do not distinguish between those populations
and therefore do not help us define patient behavior. They do
not help us define patient relationships to health care status
and health care access.

We have noted extensively within our own community
center that our patients repeatedly expressed the fact that they
thought that they were safe because they are predominantly
recreational drug users, as is most drug use in this country,
frequently recreational, whether it be heroin, cocaine or
alcohol. It is a weekend phenomenon, sometimes a monthly
phenomenon. It does not classify someone as an addict nor as an
untreatable person.

These stereotypes then lead to questions. The question
is how large is the true population at risk in this nation in all
communities not only within the minority community but especially
how many women are at true risk and at what point are we going to
see the true number of cases present themselves to medical
institutions.

There is another interesting subset of patients that we
are following. These are "clean" drug users. These are people
who have been clean for greater than three to five years but
after struggling with addiction and changing major life behavior,
these people find themselves stricken with a fatal illness.

They bring their partners to us. Their partners find
that men that they accepted as men who had changed a pattern and
are now "clean." Now, they see themselves as "punished" for
having accepted a man whoever had a history of drug use. You
know, there is no such thing any more in New York City as a clean
drug addict. If you have ever used drugs, you are a tainted man.

So when you also look at the issues of drug therapy, it
becomes critical to look at the issues of intravenous drug use
not only in women in therapy, and how they respond to therapy,
but the non-intravenous drug using partners and how they respond
to therapy, how they look at therapy for their partners and how
they do or do not support any type of adaptive behavior.

53

 

 
 

 

The issues of seroprevalence and latency within the
disease especially for women are areas to examine for future
therapeutic decisions. Therapy for women is not discussed, I do
not find as a medical practitioner as a whole. The more
important question it seems to me when people speak to me is, is
the woman infecting the man or is she infecting the child. No
one asks me about the status of the women.

[Applause. ]

DR. DAVIS: Not a single research trial in this country
for HIV disease has had a significant female population, not one!
Whether we are discussing antiviral agents such as AZT or more
recently developed drugs such as Ampligen, especially when you
discuss the drug trials in Ampligen which is manufactured by
duPont which without question decided not only would they not
take any women, they would without question never take anyone who
ever touched intravenous drug use whether they were an addict or
not an addict thereby precluding all but the 37 percent, presumed
37 percent, known minority gases that are gay and bisexual males.
They left out anybody who was black, Hispanic or women, period.

[Applause. ]

DR. DAVIS: Access in general to clinical trials has
been limited for women based on women's entrance point into the
medical system, their multiple social problems such as lack of
Support structures, transportation to the centers, running
certain trials, day care arrangements and general lack of
understanding and knowledge about experimental treatment
modalities so that most women from the types of communities that
we serve that we had heard of from anecdotal references do not
seem to have knowledge that AIDS and HIV disease may be a
treatable disease especially if you present at an early point in
the disease process.

So to even start discussing co-factors, I find somewhat
unreal. It means defining ways of gaining large enough cohorts
to look at women with HIV disease from all spectrums of the
disease from asymptomatic to AIDS.

Drug testing should be done where patients are treated.
Frequently for women of color, community health centers are the
first line of treatment. Flexibility should be sought within
medical institutions to share data and research modalities.

Women in all chronic illnesses, as supported by a large number of
psychosociologic data usually bear the brunt of caring for sick
individuals within a family structure.

When you start talking about a woman who is HIV
positive and has a sick husband and may have a sick baby and this
is how she found out she was sick, that then means that she

54

 

 
 

delays her entry into the medical system even further to care for
those sick individuals within her own family. We find that
pattern repeated daily.

We would like to delineate further on local issues to
touch upon problems that we feel are important in caring for
women with HIV disease. The institution which we are affiliated
with, Woodhull Hospital and Medical Center, is a typical
community hospital in the municipal health hospital system of New
York City. It has been caring for an increasing number of cases
of HIV related disease since it opened in 1982.

The ambulatory care centers of Woodhull see over a
third of a million cases annually and, in fact, the New York City
Health and Hospitals community health centers see four million
cases annually.

Within our community even in light of increased
federal cutbacks every year since this administration began its
present reign, we operate at or above capacity. Our service
community is a poor one which is born out by the 1980 census
tract information. Thirty-five percent of the incomes are below
the poverty level. Twenty-five percent are below $5,000.00 per
year. Fifty percent are below $10,000.00 per year.

All health indicators such as cirrhosis, infectious
diseases, increased infant mortality are well above New York City
rates. Our ambulatory AIDS treatment unit was opened in July of
1987. Referrals are from anonymous testing sites, physicians and
primarily from patients. Our clinic sees approximately 700
patients in a general medical population per month but of that
percentage, a mean number of 130 cases are HIV related disease.

We have an active case load of 300-plus HIV patients.
Eighty percent of those cases are of color. Hispanic is almost
50 percent. Black is approximately 40 percent. Haitians are
five to ten percent, and the others include whites as well.

Women comprise approximately one-third of our present
HIV case load which increases every month as women tell women
that there is a place where you can go where someone speaks
Spanish, where someone is of color, and where a lot of the
practitioners are female.

We offer testing, counseling and general medical care
including drug trials to our patients. Even our statistics are —
not consistent with other figures as previously cited. We have
difficulty with the incidence figures as cited of seroprevalence,
since within our own testing which is totally voluntary and is
primarily of women who present themselves saying, "Oh that dude
I might have dated ten years ago, maybe he used drugs." We have
a 28-percent seropositive rate in asymptomatic women.

55

 

 

 
 

 

Counseling is a dramatic process within our clinic and
the need is compelling within our community. We begin with one
target case and often end up counselling and treating family
members whether HIV positive or not. This labor intensive
process in any situation becomes acutely severe for us due to
issues of homelessness within the community, ‘unemployment --
especially as households lose their female wage earners, lack of
insurance, which limits visits to the clinic and real issues of
discrimination based on the fact that you have HIV disease, that
you are female and that you are of color.

It often takes weeks to months for us to treat either
the male or the female sexual partner or to have them come in,
because of the need for wage earnings within the household.
However, our patients return for a re-visit rate when they enter
the system that would make any private or public institution

happy.

Although we have not adequately studied the reasons
why we believe this is because we provide one of the few places
where they can openly discuss their disease, we provide group
support, and we can discuss issues that cannot be discussed in
the community at large, especially within the Black and Hispanic
communities. You do not go around telling people that you have a
bisexual husband, and that this is the way you found out you
have HIV disease.

We attempt in these counseling sessions to empower our
client, which is very important to us. We wish them to be able
to discuss issues, we wish them to be able to deal and cope with
their illness as well as to learn how to live with it to the best
extent possible, and we try to help them to educate their own
surrounding community.

Treatment of HIV disease is limited by the number of
staff people and the resources of a very strained municipal
system. We are able to offer AZT, for which we have not noticed
significant sexual difference thus far although we have not yet
correlated all our data, and in coordination with another
community-based research initiative have instituted disulfiram
and aerosol pentamidine in studies as well, and we hope to have
more drugs available within the next three months.

Here then is where we think perhaps the Federal
government can step in. First and foremost, the real importance
of community health centers must be realized. We area primary
link to under-served populations.

(Applause. ]

When you speak especially about populations that are
high in terms of low insurance rates, that they have low income,

56

 

 
 

 

they're poor and they're undocumented -- you're looking at the
physicians. who take care of those type of populations. Further
federal cutbacks will lead to a further diminution of quality of
care in community health centers. As it presently stands, we do
not have significant numbers of outreach workers in the community
to educate the populace about a disease that is now best handled
within the "medical best knowledge" with preventive behavior.

Multiple studies have documented changes in behavior
among the "hard core group" of intravenous drug users who may not
have stopped using drugs but they do stop sharing needles. They
do learn how to use bleach. If you can change behavior in the
"untreatable" group with prevailing medical presumptions, then
certainly you can change people who do not even have that
underlying behavior as their risk behavior and risk factor.

Further, monies are needed to support efforts within
the community to educate and protect itself such as ADAPT, a
group of prior intravenous drug users within the New York City
community. Staffing in our institutions for support services
such as social workers, technicians, community outreach workers
is stretched to an unbelievable point that I find hard to
describe to you here today. In our facility, we reached
saturation three months ago. Now remember, we opened in July.
Our numbers have increased steadily every month.

Municipal systems have not been able to adequately
subsidize salaries. This limits our ability to retain and
recruit staff, especially when dealing with nationwide problems
such as the nursing shortage. Loss of designation as medically
underserved areas, especially during the time course of this
administration, hurts us for the recruitment of physicians and
other health care workers. Perhaps in the solving of individual
problems, for example, one real practical solution we can give is
physician indebtedness to the Public Health Service. AIDS
ambulatory care facilities should be given priority status. We
can use all the doctors we can get.

We would also like to note that AIDS is another case in
point that should really be looked at in the context of the full
health care within the community. It is the last insult ona
number of insult. It is not an isolated disease in an otherwise
healthy community.

When women cannot have enough money to support their
families, find adequate housing, feed their children and pay for
medical bills, they drop out of a wage-earning system. Most of
our women enter our system working; they quickly have to stop.
They do that because Medicaid provides transportation, medication
and other ancillary benefits.

57

 

 
 

 

 

Housing is a major and critical issue and cannot be
looked at outside of the AIDS issue. It is -- especially for
low-income communities when you talk about crowding, poor living
conditions and no place to house sick people, especially if you
have a sick woman with three children, then you see, the way the
present system is structured there is nowhere to put a woman like
that when she lost her apartment because she went into the
hospital and she was sick for a month from PCP and she farmed her
children out to her family -- this is a real incident. She lost
her apartment, there's nowhere to put her. So then the Bureau of
Protection for Children in New York City came and took her
children away. It's either that or they must give their
children away for adoption. Obviously, family structure is not
considered important within the context of the overall health
care of the initial patient. Housing initiatives are therefore
desperately needed, especially for women with AIDS.

Equal rights and the lack thereof is also frequently
set in tone by the Federal government. I think it is critical to
understand the impact the Federal government can have in this
area where all trials should be open to any individual who
complies with the rules of the treatment regulation. It is
discriminatory to do otherwise.

[Applause. ]

There is a lack of coordination between major medical
institutions and local community medical institutions. There is
a vast amount of data that is just not being looked at, it's not
compiled. When you have two doctors and two nurse practitioners,
it is difficult to look at the data when you're seeing 19 to 20
cases a day. There is just not enough time, there's not an
epidemiologist on service, and you don't have a computer.
However, the Federal government could certainly step in by asking
bodies such as NIH to compile data if it was sent voluntarily by
those institutions so that large patterns of change in the
disease and who it affects could easily be seen in that type of a
setting.

An initiative on drug abuse and therapy is critical,
without statement. What this epidemic may help us to really
define is common behavior in all our communities across this
entire nation that is hidden. It should be remembered in the
process of teaching about HIV disease, you teach much, much more
about health care and we have been able to see real change. I do
not believe that the gay model in which that community was able
to turn around so many things such as sexually-transmitted
diseases, the decreasing incidence of gonorrhea, et cetera, and
changes in actual behavioral patterns, cannot be replicated in
any community within the United States.

58

 

 

 
 

 

Our government, insofar as positions in the front line
aspect of coping with women with AIDS disease, in addition to all
the other health problems of the population, we are astounded at
the stigmatization presently occurring within the media and the
presumption that a stigmatized patient who will get AIDS has to
be either Black, Hispanic or a chronic intravenous drug user,
this is just not qualifying, it's not correlating with the data
we are collecting.

Ignorance -- we remember the War on Poverty. The three
women you see right here were born at the institution of such.
We cannot believe that the end of the War on Poverty is going to
be the benign neglect and ignorance of a major epidemic that can
change the entire face of this nation, and that this is the only
answer this nation has to offer.

[Applause. ]

DR. LILLY: We will now have a questioning period. Dr.
Davis has given us an extraordinarily detailed presentation and
we will now have a brief questioning period. Perhaps we could
start with Ms. Pullen.

MS. PULLEN No questions.
DR. LILLY: Dr. Primm?

DR. PRIMM: Dr. Morgan and Dr. Davis and Ms. Ribble, I
want to thank you for a very complete presentation, and I'm sure
that as well as I am very proud of what you have said today, that
unquestionably your father, who I served with in the Army as you
know, would also be very proud, Dr. Davis.

I'm happy that you cite the study that was done at the
Addiction Research and Treatment Corporation that you are
involved with on an ongoing basis in your own work, where a
number of men who are intravenous drug users have as sexual
partners non-intravenous drug-using women who certainly are more
than likely to be positive for the antibody to the virus.

I noticed something else that you didn't talk about in
your presentation. In this week's Sciencé magazine, or last
week's Science magazine, I don't know whether you read that
article that talked about oral contraceptives may be making women
even more susceptible because of the kind of receptivity that's
created in the endometrium when oral contraceptives are used.

And you all might want to look at that factor as a co- factor in
the seroprevalence or the incidence and prevalence of the
problem -- infectivity among your patient population.

59

 

 
 

 

Again, let me commend you. I have no questions. Your
presentation was complete and succinct and with great candor, and
thank you very much for that.

DR. LILLY: Dr. Crenshaw.

DR. CRENSHAW: I also would like to thank you for your
presentation, and you raised so many important points, I'm sorry
to be limited to address just a few because I think this issue
deserves much more time and airing.

In a disease that kills two generations at once, we
tend to focus on the babies, as indeed they deserve the
attention, but the women often get lost. I really am troubled
that this far into the epidemic there are destructive articles
such as have appeared recently, minimizing the threat to
heterosexuals, to people in general. I think it kills people, I
think they lower their guard, and I think we need to be more
responsible. And even if we're wrong, if we're inadvertently
exaggerating the threat, we'll save lives and we'll be careful.

So I completely agree with you that we need to learn
the extent of the disease among women so that we can respond and
address it better. I have, long before the AIDS epidemic,
struggled with the problem -- and you're probably aware ~- that
in all drug research, long before the AIDS issues, women are
considered as modified men. The studies are done primarily on
men unless it's endocrine or birth control, and the special side
effects that could affect women in very devastating ways aren't
addressed.

I would love to have help on how to change the
situation, and maybe this is one of the positive spin-offs of
research in AIDS because women will have to be completed in these
studies, and they need to be entered now, five years ago, not
five years hence. So anything you can give me on good ideas on
how to encourage all of the research to address the special
problems of infected women I would be most receptive to.

MS. RIBBLE: Could I comment on that? I'd like to make
two comments. I think the first comment is that one way the
Federal government has of directly addressing that issue is to
mandate to the FDA that no drugs will be released unless they
have been tested in women, and that the recruitment of women into
studies will begin immediately, that they will back- recruit into
studies that don't include women at this time, and that they will
really make an effort to recruit minority women.

And I also want to include not just women but the

straight men, for example, who have also been excluded from those
studies. You know, not every man wants to go to a study and

60

 

 
 

 

pretend that he's gay or bisexual to get a drug, which he may
not get because he might be getting a placebo.

My second very strong recommendation is that the CRI
has an initiative which is to provide treatments that have been
shown in modified testing to be safe and that need to be reviewed
in terms of efficacy and to not do placebo control trials on
drugs already shown to be safe. Women could certainly benefit by
having more CRI type drug trials and less scientific testing that
demands that you will denote the effectiveness of a drug based on
how many people in the placebo group die.

DR. CRENSHAW: Thank you. And I might also add that I
think in the area of prevention women are being both misled as a
result of much of this kind of information we described, and
deluded by the lack of sophistication we have about sexual
practices and the lack of understanding that artificially
classifies as two separate compartments heterosexual and
homosexual, and women are usually the last to know what their
sexual partners are truly doing if it's something they want to
keep from them. So we need greater sophistication and
understanding, and we need women to become a little more alert
and aware so that they don't inadvertently put themselves at
risk.

DR. DAVIS: I think some statistics that can easily be
looked at -- we are part of the Community Research Initiative
here in New York, we have just joined it in the hopes of gaining
more drugs for our patients. As a physician, I do not wish to
unleash large trials of drugs that have not at least been having
some type of placebo testing in small groups because I have seen
what AZT can do in a negative fashion to people. It is really
remarkable. We do not have the same result overall that were
cited in the original study, but of course I can't give you that
kind of specific information here.

But I'm just saying that if one community practitioner
in the most drug-ridden, low-income area of New York City can
give you this kind of information, do you have any idea of how
much information is out there when you look at Harlem, North
Bronx, the South Bronx, Staten Island and Long Island. And this
is just New York City.

There's a National Cancer Registry. Wy can't we have
national statistics on AIDS on what treatment has done for
somebody at somebody's clinic. I mean, there's Medlines. We can
all plug in. I'll go to the local library and plug in my data.
And the NIH I do think is capable of doing that.

I do think also the Community Research Initiatives need
to receive more funding in terms of the RFP process -- you know,
that's a difficult process to mount. You're talking about

61

 

 
 

 

statisticians, et cetera. When you look at the RFP process
Someone who is in a cummunity project like myself really doesn't
have the capacity to necessarily get an NIH grant. I can assure
you it won't be due to lack of determination.

However, the reality of the process is that if I'm
seeing 19 acutely ill patients a day, counseling, treating,
running a group three times a week, I need some kind of help. We
cannot take anymore cuts in funds in community health centers.

DR. CRENSHAW: You're doing a remarkable job with a
paucity of funding, and you are a remarkable example that shows
what is possible, not what's impossible, so thank you very much.

DR. LILLY: Dr. Walsh?

DR. WALSH: Dr. Davis, I had to step out because I was
talking with Mr. Delaney about what he and Mr. Hannan are
interested in, in trying to clarify a way to get some of these
things to help you and to clarify a strategy because we didn't
have time for questioning, so I missed a little bit of the early
part of your presentation.

When I came in I think I heard you say, however, or
point out the much greater incidence in women of HIV positivity
than has at least been reported. And I was wondering, you know
this Commission is informed on a weekly basis by CDC of the
incidence of disease, the distribution of the disease and where
it comes from and so on. And it just seems to me that those
figures, as I see them, don't represent anything like what you
are talking about, and I'm sure it's not intentional on CDC's
part to --

DR. DAVIS: No, actually cDC is now coming to look at
our community. We called them, we told them. We have a 46
percent rate in men -- 33 percent in children.

DR. WALSH: This is what my concern is because I share
what Dr. Crenshaw has said; this sort of complacence that there's
not much heterosexual transmission, that women are not getting
the disease, and I think that we may be living in Fairyland on
that.

DR. DAVIS: I can assure you, you are.

DR. WALSH: It just isn't true.

DR. DAVIS: I don't mean to be facetious; I just am
telling you the numbers rise every day.

DR. WALSH: But again, I think it also supports so
strongly the position that Mr. Hannan and his colleagues took

62

 

 

 

 
 

this morning of how much more use can be made of the community-
based efforts. And this Commission has to find a way to do that,
or to urge it. We can't do it; we can urge it. And I just think
it would be helpful to us, certainly to me, if we could get more
frequent information from people like yourself telling us exactly
what's happening in the real world, and maybe in a sense you
share the responsibility to the extent that maybe you get
impatient with them because I'm sure you send them statistical
information; maybe they just don't accept it or don't use or
whatever. Who knows?

But for some reason, it's not surfacing, and I think
it's important that the Chairman be able to include in his
recommendations to us as the Commission the fact that there seems
to be something wrong with this statistical information, and ways
in which we could take samples to correct it. Because again,
this would benefit the efforts at treatment that you want, the
efforts at getting more funding that you want or more diversified
funding. And I would be very grateful.

But I did hear you correctly, then. I was astonished
at what I thought I heard. And I am sure this can be replicated,
as you said, not only in Bushwick but in Staten Island and in
other places, which means to me it's a much greater problem than
the country has been led to believe. And when we're criticizing
high officials in the administration, keep in mind they're only
getting the same official information, also, that we're getting.

DR. DAVIS: Well, please take my information straight
to them.

DR. WALSH: So that's what you have to do.
Unfortunately, they don't get it. But you know, those things --
I wish it were true. I wish that everybody who wrote a letter in
some way that it would get there but it doesn't.

But I think that we can get it to them through this
Commission, and I think it's very important that we find other
sources of data so that we can raise questions. We have no basis
to raise them unless we get that information.

And I want to thank you for waking us up.

DR. DAVIS: Thank you. Can I just respond a little bit
to both of you. I think one other major problem is that -- and
I'm very aware of this. I chose to be a public health physician,
and I think that often physicians of my generation, especially of
my racial and sexual background, have chosen this path. However,
it also means that when you talk about the liaisons between
public and private medicine, let's just be very real. That's
that world on that side of town, and this is this side of the
tracks. There is no question that the Federal government

63

 
 

 

supports private institutions and public institutions. You all
can make rules -- or rather, the federal institutions can make
rules about how much has to go across the tracks; I don't care if
it tunnels under or if it goes over, but it does have some
control over those issues.

It's real important ~- community health centers can't
take AZT levels, but most women in New York City receive AZT in
community health centers. I can't get an AZT level; you think I
an afford to pay for AZT levels? Who's going to pay for it?
Burroughs Wellcome is making too much of a profit; I've already
asked them. There has to be greater cooperation. It's a
national epidemic; it's not only in Bushwick, you know. It's not
only in Brooklyn.

Sometimes it seems to me when I go to conferences with
other physicians, there's a real lack of saying if you bleed, I
bleed. You know? There's a real lack of understanding that it
really is one nation with many diverse populations.

DR. WALSH: Again, shouldn't Medicare and Medicaid, for
example, pay for the experimental drugs? That's something the
Congress has to handle; that's something that maybe we should be
recommending.

DR. DAVIS: Or a protocol to establish such.
DR. LILLY: Mr. Creedon.

MR. CREEDON: I really don't have any questions but I
think that the testimony has been very valuable, and as Dr. Walsh
says, it proves the importance of groups like your own and Mr.
Hannan's; the local groups are really going to make the
difference here. The Federal government can't do it all; they
can help pay for it but I think efforts of groups like yourselves
are going to make the difference. Thank you.

DR. DAVIS: But there is a differential in front of you
now. New York Hospital does get more than Downstate Medical
Center.

MR. CREEDON: Well, we have to address that.
DR. LILLY: Dr. ServVaas.

DR. SERVAAS: Thank you for coming. I really like
your suggestion about a national AIDS registry, and I'm surprised
that we don't have one, like the National Tumor Registry. I
wonder if you could tell us in your own observation -- I've heard
conflicting advice from different sources in the country -- about
women when they become pregnant. Do you observe that they are

64

 
 

bend ne)

more likely to become ill with AIDS when seropositive women
become pregnant?

And then I had another question. I don't know how many
women you have who are HIV antibody-positive, but would these
women, in your opinion,: be. willing to try non-toxic preparations
to see if. they could go on longer and not get ARC or AIDS? In
your opinion. ;

DR. DAVIS: Let me answer the second question first
because it is actually easier for us. If I can be so asinine,
the day when we called DuPont we literally had a face-down about
Ampligen. The two of us stood in the hall and cried, and our
patients surrounded us. Our staff continued to surround us until
you had 29 crying people in the hallway.

Our people beg us for treatment. In the media, there
is not sufficient knowledge, especially because I think
especially in the minority communities people feel so
stigmatized, it's like you're saying these are not bank clerks,
which they are -~ most of my women are bank clerks, they're the .
people who serve you at McDonald's, they're the people who have
low-income jobs in society, and you're saying that they have
given nothing of value in the society. And so they don't come
for treatment often, and they hide all aspects of their disease.
So that when I'm not able somehow to put them into that systen,
they just give up. It is just unreal.

There's no question -- we're using disulfiram, which as
I'm sure you all know follows the principle of DTC and is a
T-cell stimulator. We're using that because it's a drug that New
York City Health and Hospitals Corporation already has; I don't
have to write but a certain number of protocols and I can put it
on the streets today, which I've done.

DR. SERVAAS: So how many women could you find who are
seropositive who would likely participate in --

DR. DAVIS: All of my women participate in drug trials,
if allowed. I have over 100 women now.

MS. RIBBLE: And I have another 135. And I have some
who would fly in from Wisconsin if, they could get Ampligen,
because that's how far my phone calls come from.

DR. SERVAAS: And have you observed that women, when
they become pregnant, become ill more quickly than the women who
are seropositive -- .

DR. DAVIS: I don't think we can adequately respond.
We are both internists; we tend to see a general medical
population. We're picking up HIV disease from our hypertensive

65

 

 
 

 

lady who says, well, I know you have this program here and my
husband did that 10 years ago so can you just test me? Do you
understand? So we're coming from a different base of population.
We get women after they've had a baby and after the baby got sick
and somebody said you'd better go get HIV tested over in that
clinic. So I would prefer not to give improper data.

DR. SERVAAS: Thank you.
DR. LILLY: Dr. Lee?

DR. LEE: Dr. Davis, first, I wonder, because we were
given so many figures, if you could give your epidemiologic
stats on your patient population to us in writing. Could you do
that? I'm not asking for a document; I'm asking for what
percentage of what population that you're seeing is positive for
HTLV. Maybe you've got three or four subset numbers. I'd like
them. And I'd like to know exactly what population you're
looking at in Bushwick. Okay?

DR. DAVIS: I would love to give them to you.

DR. LEE: Number two, I cannot get a handle on really
what effect the bisexual man is having on women. When I look at
the patients, my gut feeling is that it would have been very
large; that women have a bad exposure at a high level, but
looking at statistics, I can't find that.

Now, you say you're seeing it, and I'd like to know.
Do you have anything specific on that? We can't come up with
that number.

DR. DAVIS: First of all, we're citing New York City
incidence numbers right now. We've only been in reality for six
months, Dr. Lee, so you can understand how upsetting these
statistics are to us, too. If we collected this in six months,
what are we going to collect in a year?

We are finding the prevalence rates of bisexuality to
be much greater than that of homosexuality among both Blacks and
Hispanics. I can't give you a number. I give you my word, I
will go home, look it up and send it back to you.

DR. LEE: If you can find something, I would be very
interested in that.

SPEAKER: Why?

DR. LEE: Why? Because this has a big effect on, or
should have a big effect on women's attitudes towards sex. One
of our conferences in April is going to be focused on the drug
abuse problem, the family, difficulties in the inner cities that

66

 

 
 

 

seem to promote drug abuse, the high level of single parent
households in this area; the problems that women are facing that
seem to us in our research are getting worse in these
communities rather than getting better. And we'll be in touch
with you, Dr. Davis, to perhaps participate in that conference
in some way.

Lastly, I didn't get from you -- are you really
involved with the Community Research Initiative? I sensed
hesitation in many ways. Now the reason I'm saying this is I can
guarantee you that this is going to be a prominent part of our
Interim Report. I know we're going to be strongly supporting
these Community Research Initiatives. We have been told that
there is a very high level of receptivity at the NIH for these
efforts, and we have been told that the funding is coming very
rapidly for this.

So personally, from what we're seeing, I would urge you
to join forces with these people rather than try to do it all on
your own. Now, am I wrong there?

DR. DAVIS: Oh, no. I just ask that you fund them
sufficiently. I have no secretary, I have no epidemiologist, I
do not have a computer --

DR. LEE: Well, they do.

DR. DAVIS: They do, but they have to use it for their
work. There are three community health centers such as mine in
New York City alone that just are devoted to a general medical
clinic with an AIDS treatment unit within it. Then if you start
talking about the local physicians that we hope to pull with us,
somebody's got to collect that data. So they've got to be given
sufficient funds to give us that kind of administrative,
bureaucratic support. The community health center doesn't have
it.

DR. LEE: As I understand it, these people do, though.
They have volunteers, they're very well organized, they have
funds. They're going to get more funds, and I would say --

DR. DAVIS: Wonderful.

DR. LEE: If I were in the community, I'd join forces
with them. Mr. Hannan, would you like to comment on this?

MR. HANNAN: I met Dr. Davis two days ago when we were
giving testimony at Albany, and at that time she wasn't familiar
with the fact that our IRB had insisted that IV drug users and
women be included in our Ampligen trial.

67

 

 
 

I am so incredibly encouraged by the fact that groups
such as Dr. Davis' group are willing to join forces with us
because it has to be a team effort. We need more people in our
trials. Those people need to get the substances which they
deserve before they have yet been approved as therapies for AIDS.

Thank you, Dr. Davis, because your testimony was
brilliant and I'm so proud to be cooperating with you.

(Applause. ]
DR. DAVIS: Thank you, Dr. Lee, for the support.

DR. LILLY: I would like to ask just one very brief
question. One thing that you said just in passing that I think I
agree with you on but I'd like just a couple of comments and I
hope it won't take me terribly long.

You said that although gay men were able to get
themselves together very early in the epidemic and to, ina
sense, take charge of their own lives and form organizations and
help themselves out to a very considerable degree of success,
that minorities and women may not be able to bring that off, and
I wonder if you could --

DR. DAVIS: Oh, no, I totally disagree with that. I
think that people are people, okay. And I really believe that
communities, even though there is this perception of the gay
community as this very well-off, middle class, white institution
that can take care of itself -- well, 10, 15 to 20 percent of my
patients are gay white men who come from the Village because they
can't afford anybody below 14th Street.

{[Applause. J

I think the whole issue of sexuality that Dr. Crenshaw
and Dr. Walsh raised and what is really known about sexuality,
lower income and especially when you're talking about poorly
educated gay men, whether they're white, Black or Hispanic, they
really don't know how to integrate into a GMHC, and it's not
because of GMHC. I'm going to tell you, I wish to give credence
and support for what gay people have done for all people's lives
in this country today.

I think, though, that you must deal with cultural
issues. You know, homophobia really exists in this country.
That's not an illusion. And when you talk about Black and
Hispanic communities, homosexuality is really not part of our
cultural norm in general; this issue has been discussed in
national Black magazines like Ebony, Jet, and Essence. We
really, as a culture, often do not tolerate it. When you start
talking about religious aspects of our community, which is -- if

68

 

 
 

 

you remember, we have come all the way from King through Jackson
-- the church has been a major source of political power. It has
been a difficult coming together.

; I do think that the communities can be mobilized. I'm
just saying that you have to look at different aspects of the
community to decide where to mobilize it. Some of the groups
that are mobilizing I can tell you right now within our community
are gay, bisexual men, the National Conference of Negro Women.

We hope to try and apply and go to various sororities,
fraternities, certainly. But that type of network -- just like
GMHC -- didn't start yesterday; it started out with 20 volunteers
and people who were dying of AIDS and were committed to giving
something back before they left this earth. And I think what
you will be seeing is that process replicated for women, for
Blacks, for Hispanics, for whoever gets touched by a disease
where they hold their child while they die.

DR. LILLY: I certainly hope you're right. I would be
very happy to see it. Admiral Watkins.

CHAIRMAN WATKINS: Dr. Davis, we're going to be making
recommendations here in the very next few days on our Interim
Report to the President, and I think your testimony and that of
Ms. Ribble has been very important to us today. I know it's been
difficult for you to get the kind of support you need in many
areas, and so we'd like to take your written testimony that you
have and your handwritten notes there, if we can, and let us
photocopy it while we have the staff to do that. So we don't
want you to get out of the roon.

The reporter here will eventually give us that piece of
information through the transcript, but I think we could use it
right away if that's acceptable to you.

DR. DAVIS: We will do our best.
CHAIRMAN WATKINS: We can do it for you.

DR. DAVIS: It was only through the kindness of the
network that exists among those of us who work with AIDS that we
were informed 36 hours ago that we would be testifying, so we
will write it up today. We have been up for the past 24 hours.
We will type it this afternoon.

CHAIRMAN WATKINS: I merely meant to have copies of
your handwritten notes, if that's something that you would be

willing to let our staff have to trigger our thoughts off as we
prepare our Interim Report.

DR. DAVIS: Okay.

69

 

 

 
 

 

CHAIRMAN WATKINS: Another question, just one question
for either one of you two. If the Federal government were to
directly fund community-based drug trials, let's say through CRI,
for example, and with your new affiliation, close affiliation
with CRI, how could we include your organizations in that? And
would that be a logical way to move with this CRI under this
federal funding mechanism?

DR. DAVIS: I'm sorry. You're asking whether we wish
you to directly fund the community health center, or you're
asking whether to directly fund CRI? I think I've missed the
question.

CHAIRMAN WATKINS: We were talking earlier about the
linkage between your organization, say, and the CRI trials where
women would be included and drug users would be included. I'm
just asking the question would this -- how could we include your
organization as part of that effort were additional funding to go
to CRI to conduct trials, along the lines that both you and
former witnesses have recommended this morning for women and drug
users?

DR. DAVIS: I think money has to -- I mean, with CRI
here in New York City, I am not frightened of the fact that
minorities and women -- they've obviously got outreach efforts
trying to adequately serve those communities, and we will attempt
to help them organize as well as we can through the network of
people that we are aware of. However, I think it has to be
specified. I think the same laws that exist for discrimination
on the books right now have to be applied to medical care.
Medical care is not an option always in this country; it is often
a privilege.

DR. LILLY: The Commission is very grateful for your
participation this morning. It's been unusual; you have said
many things that we had not heard before and we certainly will
take them into close consideration in our further work. And
thank you.

(Applause. }
HIV Infection Co-factors

DR. LILLY: There are three speakers in the next panel
on Co- Factors who are going to speak to us with respect to
things that are not perhaps the direct cause of the epidemic but
play strong factors in its occurrence.

Our first speaker in this session is Dr. George
Solomon, who is Professor of Psychiatry at UCLA. We would be
very grateful if the speakers could keep their presentations
relatively short and concise.

70

 

 

 
 

 

DR. SOLOMON: I think I shall start by referring to
psychoneuroimmunology that began over 20 years ago, but really
is burgeoning at the present time as a result of realization. that
the immune system is not really autonomous but is influenced by
neuroendocrine mechanisms. For example, there was a conference
late last year co-chaired by me and Dr. Lydia Temoshok sponsored
by NIMH on the relationship of psychoneuroimmunology to AIDS
research.

Psychoneuroimnunology is concerned with complex bi-
directional, two way, interactions between the central nervous
system, which not only mediates psychological but also biological
processes, and the immune system. The immune system itself is
not only responsible for resistance to infectious diseases and
cancer, but also is being found to play an important
bio-regulatory function. This field reinforces the view that all
disease is multi-factorial and bio-psychosocial in onset and
course, and the result of interrelationships among specific
etiologic agents, such as bacteria, viruses, and carcinogens, and
genetic, endocrine, nervous, immune, emotional and behavioral
factors.

As a result of the various hypotheses and postulates of
psychoneuroimmunology that began a number of years ago with a
single one, that stress could express immune function and now
number some 40 odd, there are hypotheses that can be derived that
are more specifically applicable to AIDS, and I would like to
mention these very briefly.

These questions include:

--Are stress or other psycho-social factors related to
vulnerability to HIV infection? We certainly know that
homophobia, for example, may make the gay lifestyle a
particularly stressful one in certain circumstances, and
certainly a drug abusing lifestyle is full of emotional
distress.

~-Is pre-existing immunosuppression a facilitating
factor for infection and seroconversion? We know that some
infections, such as Epstein-Barr virus infection, can be
immunosuppressive, but we also know that drugs, particularly
exogenous opiates, and emotional distress can be
immunosuppressive.

--Can stress activate HIV from a latent to a rapidly
replicating state? It is now known, of course, that HIV can
exist for long periods of time in a latent, low replication
state. We also know, and there is good research, that stress can
activate other viruses, particularly the herpes viruses. The
discoverer of the tat gene -- transcriptional activating gene --

71

 

 
 

 

himself referred to stress as a possible cause of activation of
that gene, one of the two genes that can activate HIV.

--Are psycho-social factors related to progression of
HIV disease? In seropositive asymptomatic individuals, there
are varied courses of drops in helper T-cell, T4, numbers. Some
people's numbers gradually decline. Others have a more rapid
Slope of decline. Some people's plateau out. Some declines are
quite flat and then suddenly begin a rapid drop. Research
currently underway by Dr. John Fahey and Dr. Margaret Kemeny, at
UCLA, is hoping to see whether psycho-social variables can
influence the decline or steadiness of immune function in HIV
antibody positive asymptomatic individuals.

~-Can psycho-social variables be correlated with
specific alterations in immune function associated with HIV
infection? We have current evidence in persons with AIDS that
there are psycho-social correlates of a number of specific immune
functions including numbers of helper T-cells, virucidal cells,
cytotoxic cells, suppressor cells and natural killer cells and
their activity. In general, in a very over simplified summary,
one can say that better immune function is associated with
better psychological status in sick individuals and worse
emotional state with lower numbers of specific T-cells. Indeed,
there possibly may be psycho-social correlates of elevations of
sets of cells that may serve a compensatory function in the face
of deficiencies of helper T-cells induced by the virus. In
other words, cytotoxic T-cells or natural killer (NK) cells may
be elevated in some positive way and help out when there is
deficiency of other components of the immune system, which has to
be thought of in a complex and interacting way.

--Is length of survival related to psycho-social
factors assessed at an earlier point in time? I really wish I
could go over with you some of the psycho-social variables that
we found associated with long survival in persons with AIDS. It
has been a great privilege to get to know some of the most
remarkable people I've ever met, who are among the long survivors
with AIDS. Their remarkable emotional strength and coping
capacity and their long survival I don't think are just
coincidentally correlated.

This correlation has very important implications, I
believe, for the problem of the disease among IV drug abusers. I
also happen to run a substance abuse center in a VA setting. I
really think we are dealing with quite a different population
often times among such individuals who almost by definition are
non-copers, using very maladaptive and self-destructive means of
dealing with life and their problems. I think psychosocial
factors such as poor coping ability, as well as continued
substance abuse, may well account in part at least for far

72

 

 
 

shorter survival of drug abusers with AIDS, on average, than gay
_ persons with AIDS.

At any given level of deficient immune function, do
psychological factors relate to presence or severity of secondary
disease? Again, we have seen a number of people who, just
looking at their immune function on laboratory tests, seem in
very bad shape, but they are doing quite well Clinically. There
seem to be some psycho-social correlates of the relationship of
any given level of immune function to the severity of clinical
illness.

Can psychological interventions ameliorate the stress
associated with AIDS and ARC and improve immune status and the
clinical picture? Research again at UCLA by Doctor Sheila Namir
shows that group interventions that are aimed at improving coping
skills are not only supportive but having to do with active ways
of dealing with the problems associated with the illness,
markedly decreased emotional distress. Current studies are now
underway to determine whether these decreases in distress are
also associated with improved immune and clinical status.

I'd like to make basically three recommendations. ‘The
first is that any social policy that is developed for dealing
with the HIV epidemic take into account the role of emotional
distress that may be engendered by whatever that policy is. In
view of the fact that there are so many people who are already
infected and asymptomatic, how policies affect how one feels
about one's self, one's place in society and what sort of support
one is getting, may have a great deal to do with the actual
rapidity of decline in immune function or incidence or
progression of the disease itself.

Secondly, I should like to recommend that psycho-
social variables along with biomedical and immune parameters be
included in as much research as possible on course and treatment
of HIV disease, in view of evidence which suggests that such
factors may play a role in progression, and perhaps even in
treatment response.

Finally, I should like to recommend that the
Government's own programs, particularly within the VA, should
serve as models. Current cutbacks in provision of treatment for
drug abuse for addicted veterans, are absolutely appalling and
in contrast, need to be expanded in conjunction with an active
program for prevention of infection as well as for psycho-social
support of those already infected.

I could go into detail about expanding programs to help
addicted veterans, many of whom became addicted in VietNam. I
wrote the first paper on drug abuse in VietNam and testified in
Congress about that in 1971. The Government itself is cutting

73

 

 
 

 

back its own programs in these areas. For a long time, the VA
was not even offering voluntary testing for asymptomatic at risk
individuals. I think that is utterly appalling, along with cuts
in staffing and duration and intensity of treatment for IV drug
abusers.

Those, essentially, are my recommendations, again
emphasizing that we should not separate psycho-social and
biomedical research, but should integrate then.

Thank you.
DR. LILLY: Thank you, Dr. Solomon.

The next presenter will be Dr. Elinor Levy of the
Boston University School of Medicine.

DR. LEVY: Thank you. I would first like to say that
primarily I'm an immunologist, so my remarks are those of an
immunologist with an interest, strong interest, in AIDS.

I have a brief statement. Each year, we learn a little
bit more about the natural history of HIV infections. We now
know that following infection with HIV, some individuals develop
AIDS within a year, while others remain without any symptoms for
at least seven years. Similarly, we know that some individuals
with Kaposi's sarcoma die within months of diagnosis, while
others live longer than six years.

At this point, however, we have little evidence or
information to explain the differences, these variabilities, and
therefore we're unable to advise the one to two million,
estimated one to two million Americans infected with HIV how to
maximize their longevity. Should they change their habits, their
diets, their attitudes?

I personally believe that the focus on drugs alone is
too narrow a focus. There is evidence that suggests, as Dr.
Solomon has mentioned, that these factors, including nutritional
ones, may have important influences on the progression of
HIV-related diseases, and I was pleased to hear the Commission's
interest in the large number of healthy seropositives. Very
little at this time is being done to look at what co-factors are
involved in progression to clinical symptoms and frank AIDS.

I will concentrate my remarks on nutrition as a
possible cofactor in HIV-related disease. In general,
malnutrition is associated with a significant impairment of
immune response. The immune response is also sensitive to
deficiencies and excesses of single nutrients and to the quantity
and quality of fat intake. Nutrition can be shown to affect

74

 

 
 

 

susceptibility to a variety of infectious agents and is
implicated in the development of cancer.

I have been involved in a pilot study of men with
AIDS-related diseases who chose to follow a macrobiotic regimen.
This regimen includes a vegetarian diet, a change to a healthy
lifestyle, and a sense of hope and control. The large majority
report an improvement in AIDS-related symptoms and additionally
in the group with KS, we've also seen an increase in the number
of lymphocytes, a significant increase over the first three years
after diagnosis. Six out of 19 of these men are alive now more
than three years after a diagnosis with KS.

Research into nutrition as a cofactor for the
progression of HIV-related diseases is difficult for several
reasons; among them, prevailing research priorities, the
complexity of studies in this area, and certain methodological
problems.

Research priorities have focused on finding a cure and
developing a vaccine, both worthwhile but still elusive goals.
Only: recently has there been a shift to improve education to
prevent HIV infection and an interest by ADAMHA in the role of
psychosocial factors, including alcohol and drug abuse, in the
progression of AIDS.

The group we have been studying is an example of the
likely interrelationship between nutritional, psychosocial, and
behavior choices. Studies must take into account these
interrelationships in order to interpret data correctly.
Additionally, there are methodological problems in accurately
assessing nutritional status, especially in AIDS where absorption
may be a problem.

I would recommend that the NIH foster more of an
interest in nutritional and other co-factors through
organizations of small workshops, such as that organized by Drs.
Solomon and Temoshok having to do with psychosocial factors, to
bring together the multidisciplinary talents needed to work out
design and methodological issues and by encouraging research
through RFPs.

I would recommend that nutritional components be added
onto ongoing natural history studies, and/or that new studies
focusing on psychosocial and nutritional factors be encouraged,
including those with intervention designs.

Finally, I would recommend that the NIH create

multidisciplinary review committees to properly review these
grant applications.

75

 

 

 
 

In view of other testimony this morning, I would also
suggest that the CRIs and other informal, community-based data-
gathering organizations include information on alternative
therapies, including nutritional approaches, to their database.
Many, many people who are at risk are trying alternative
approaches, and that shouldn't be ignored.

At this time, I cannot give an estimated cost for
implementing these recommendations, but suggest it would be a
modest investment compared to what would be saved in health care
and social service costs if onset of debilitating symptoms can
be delayed or prevented.

Although the state of our knowledge about the factors
predisposing to the progression of HIV infection is not
extensive, it is still likely that these co-factors play an
important role. There is an urgent need for research in these
areas, so that accurate information can be used as a basis for
more effective treatment strategies and educating persons at
risk.

Thank you.

[The prepared statement of Dr. Levy is included in the
Appendix. ]

DR. LILLY: Thank you, Dr. Levy. I certainly would
agree that nutrition studies have often, in many senses, been the
poor stepchild of the biomedical world.

Our next speaker is Dr. Peter Duesberg, who comes to us
from the University of California in Berkeley, where he is
Professor of Molecular Microbiology.

DR. DUESBERG: I thank the Commission.

The hypothesis that the AIDS virus is the cause of
AIDS, as we heard on many occasions yesterday and today and the
day before yesterday when I wasn't here, I assume, is the basis
for a $1 billion research effort in this virus, which is by now
probably the most expensive virus in history. It is the basis
for the rather toxic AZT therapy of AIDS patients, and, in fact,
that is now being extended as a prophylactic therapy for those
who have no symptoms yet, and it is also the basis for the famous
AIDS test, which is, to say the least, at least psychologically
somewhat toxic, at least to some people who commit suicide or get
their homes burned down when they are positive.

Now all of this would be highly justified, of course,
if we indeed knew that the virus is the cause of AIDS, but I
submit to you that I don't think this is proven and there wasn't
any time to prove it. The scientific community was under

76

 

 
 

 

tremendous pressure to come up with the cause for AIDS, and in
this rush to come up with the answer, probably many questions
were left unanswered, and what I think is actually worse, many
questions were never asked.

There was no time for slow answers. There were only
fast answers, as we heard in the testimony yesterday from Drs.
Roper and Sam Broder. We had fast tests within five or six
months. We had fast vaccines. The vaccines didn't work, but we
had faster AIDS yet, and in fact we just read in The New York
Times last Sunday how many vaccines we have. None of them works.
And there were pages and pages of discussions why they don't
work, except to mention the possibility that the virus may not be
the cause of AIDS, and that's why they don't work. This may be a
rather simple answer, but too simple for The New York Times.

 

[Applause. ]

Now what I would like to address today in the little
time that I have are the problems that I have with the
hypothesis, the questions that haven't been asked, and answers --
I don't have too many answers unfortunately, but also the
questions that haven't been answered.

One of the problems that I have with the hypothesis is
that the AIDS virus doesn't follow the rules that all other
viruses, known to me at least, and all other retroviruses known
to me, follow.

One of these rules, for example, that viruses follow,
believe it or not, when they cause a disease is, they are active.
They are biochemically active, metabolically active. They do
something in order to get something done, exactly like you and
me. When we want to get something done, we have to work for it.
It's true for chemistry; it's true for physics and biochemistry,
except for the famous AIDS virus.

That one isn't doing no nothing, as they say. That
virus is latent and inactive. In fact, it is only detectable by
the most expensive laboratories in the country, even in the fatal
course of the disease. It is no more active in those who are
dying from it -- or inactive, I should really say -- than in
those who have no symptoms whatsoever.

Perhaps the best case in point here is the famous
controversy between Drs. Gallo and Montagnier's labs where the
virus came from. It has escalated into an international
controversy between the United States and France, which was
finally only settled by Presidents Reagan and Chiriac. The
difficulty would have never happened 100 years ago when Robert
Koch and Pasteur were competing, because they were dealing with
microbes that were active at clinically relevant concentrations.

77

 

 

 
 

 

It would never have happened to Salk and Sabin either. They
were isolating viruses when they were clinically relevant at high
concentrations.

This virus is at such low concentration that it is very
difficult to isolate it. That's why we had that famous
controversy.

It is also relevant to point out, in view of the famous
AZT therapy for this virus, AZT is an inhibitor of DNA synthesis,
an analog of thymidine which when incorporated into the DNA of a
growing cell or replicating virus stops DNA synthesis right
there. The buck indeed stops right there. As Sam Broder put it
nicely, it is aesthetically pleasing to see the sequencing of DNA
when he is treating patients with that drug. He would indeed do
that only if there were any DNA synthesis.

Again, not even the most expensive laboratory in the
country can detect DNA synthesis. All they could come up with
is, in 15 percent of AIDS patients, they find some DNA, not
actively being synthesized, but that's five-year-old DNA. The
latent period, as you perhaps recall, is five years for that
virus to cause the disease.

So that AZT therapy does one thing for sure. It kills
all growing cells. Whether it does anything else, I haven't
heard any discussion about. It certainly can't hurt DNA
synthesis when it is not going on, but it may be like it often is
in medicine, like chicken soup, things have unpredictable
benefits. But in this case, it's a designer drug. One thing it
does for sure, it kills every cell in which it's incorporated.

Now another rule that viruses regularly follow when
they cause diseases, they intoxicate or infect or kill more cells
than you could possibly spare or afford to lose during the course
of the disease. That is to say, the hepatitis virus only bothers
you if it is chewing up half of your liver or a third of it. If
it claims 1/1000th or 1/10, oooth of it, you will never notice you
were infected. The same is true for polio virus. 99 percent of
all polio virus infections are latent, because the same thing is
happening as in vaccination. A couple of million cells are
killed in your guts. You make antibodies. You will never notice
it.

But only when the virus penetrates deep into host
territory, kills off or infects or intoxicates large fractions of
specific organs of the host will you experience symptoms of a
disease.

Paradoxically, the AIDS virus doesn't do anything like
that. It actively infects never more than one in ten thousand
T-cells, even during the fatal course of the disease. This is

78

 

 

 
 

the equivalent of losing one drop of blood every day
approximately. You and I could sustain that for approximately
10,000 years without changing anything. We would look exactly as
we look now.

Another rule that viruses commonly follow when they
cause a disease is that shortly after exposure, after a take, you
develop symptoms, or you don't. If you're lucky, you don't; if
you are not lucky, if you took, then you have a disease a month
or two months later. This is true for both casually and
non-casually transmitted viruses. You know a month or two months
later whether you have hepatitis, when you are stuck by a
needle, or herpes when you have had some intimate contact or
rabies when you're bitten by a dog or polio or measles or mumps
when you are simply casually exposed to somebody who has that
disease.

So that is to say, viruses work quickly or not at all.
Again, the AIDS virus seems to be the exception to the rule.
This virus is said to cause disease only after a latent period of
at least five to seven years. What it does in those five to
seven years, how it's making up its mind to cause a fatal
disease, if it couldn't do that five to six years prior to this,
is not ever explained in any of the papers I have seen.

Another cardinal rule in virus infection, in
immunology, is that viruses cause disease or at least the primary
symptoms of the disease before immunity, not after immunity. The
host, in other words, has to be permissive to the virus to let it
happen. If you are not permissive -- that is to say, if you have
antibodies, if you are vaccinated -- the virus has no show or has
not a good chance to cause a disease. In fact, typically it
doesn't.

This is exactly why vaccination works so well. Ever
since Jenner discovered the principle of vaccination 200 years
ago, antibodies were seen as evidence for a successful rejection
of the prior infection and as protection for the future. That's
why we were all vaccinated against polio, against measles,
against mumps, against herpes or hepatitis, whatever is available
in the form of vaccines.

Now the HIV establishment has reeducated 250 million
Americans to know otherwise. Now we are all educated to know if
you make antibody to this virus, this is a prognosis for death.
It's bad news. You're going to die five years from now. You can
start committing suicide or do other things.

So the AIDS test is measuring nothing but antibody to
the virus, which until a few years ago was something you should
be pleased about, you were to be congratulated for because your
immune system was intact. You could make antibody to the virus.

79

 

 
 

 

The AIDS test not only measures antibody to the virus.
It also tells us that the antibody works really well, so well
that it is extremely difficult to isolate the virus. I already
alluded to the difficulties in isolating the virus. That's a
typical example.

Unlike all other viruses, the AIDS virus is not
killing cells. It is a retrovirus. The hallmark -- wait a
minute; I have a couple of slides. I began to forget my slides.

(Slide. ]

This is the first statement I made. I will just leave
it there for a second. That the viruses have to be active when
they cause a disease.

Now I have to find the right button. Wait a minute.
This one would be it.

(Slide. ] )
Okay. This is the next one, that they have to infect a

large number of cells when they cause a disease. Again, the AIDS

virus doesn't do that. And I'll be catching up in a second.

The third one was that the viruses usually act fast or
never. The AIDS virus needs five to seven years.

And this is the immunity statement that typically once
you have antiviral immunity, you are protected. That is not to
Say that nothing is ever perfect on this planet. You can lose
it, and the virus can come back. But typically that works. With
AIDS, the rule is, the disease follows only after antiviral
immunity, at least it is said to.

{Slide. }

And here, I am at this point. The AIDS virus is a
retrovirus, and the retroviruses, unlike all other viruses, do
not kill cells. They need living cells in order to replicate, to
survive.

This is why retroviruses were the most plausible viral
carcinogens or models for viral cancer in Nixon's war on cancer.
And a number of us owe our careers to the cancer-virus progran,
studying retroviruses as possible human carcinogens. One of them
is, for example, the famous Dr. Frank Lilly, who is in this roon,
and the other is Dr. Peter Duesberg. All of us were retrovirus
hunters, because we were all convinced that retroviruses are very
likely carcinogens, because unlike all other viruses, they do not
kill cells when they infect the host. In fact, they often

80

 

 
accelerate growth. That's why they were considered possible
tumor viruses. Other viruses always kill.

_Now the HIV establishment again has educated us
.otherwise. They have said paradoxically this virus causes AIDS
by killing T-cells. I don't know the explanation for that or no
answer for that.

Another peculiarity about this virus is that unlike all
other viruses known to me -- in fact, all other microbes known to
me -- this virus is said to discriminate heavily between boys and
girls and among those between heterosexuals and homosexuals.

HIV, paradoxically, prefers men in this country, at least, with
an absolute majority of 92 percent. That's the CDC's statistics,
not my work. And even now, seven years into the epidemic, when
we always hear that this is a rather permissive and liberal
country, the virus should have made it out of these groups into
the general population. But it hasn't.

Now perhaps there is one very last comment that I
would like to make that raises a question about this virus being
the cause of AIDS. Basic logic has it that viruses that are
pathogens that are responsible or made responsible, held
responsible, for disease have to be at least present, if not
active, when they are responsible for the disease, and they
should be present in all cases of the disease. This is called
Koch's postulate, Koch's first postulate. If that one isn't met,
you don't have to worry about the second, the third, and the
fourth of Koch's postulates.

Now paradoxically, the CDC guidelines of September '87
stipulate exactly what you have to do or what you can do if you
want to diagnose an AIDS patient, if there is absolutely no
laboratory evidence for that virus, using the most sensitive
techniques that biochemistry or biotechnology has to offer. And
it stipulates in the statistics that about 25 percent of the
cases of the 1987 AIDS vintage, like approximately 3000 cases,
fit only the revised guidelines, which means there is simply no
evidence for the virus.

[Slide. ]

I made a slide here of this paper from the CDC which
appeared in the Journal of the American Medical Association.
This is a computer disk which they offer you free, how you go
about it when you want to diagnose an AIDS patient when you can't
find the virus.

See, this is easy when it's positive. Then you just

follow Dr. Gallo's or Dr. Fauci's advice. You have an antibody
positive test, and if something happens to that person, it's an

81

 

 
 

 

AIDS case, whether it's an airplane accident or a disease or
diarrhea. That's easy.

(Applause. ]

When it's unknown or inconclusive, then the cDC
provides help. This is in the table. And when it's totally
negative, you can still win. There are still possibilities here
or here. That fits in your Mac computer.

So I would conclude, then, from what I have said,
unless all of these problems can be solved, the AIDS virus cannot
be the cause of AIDS. But unlike my competitors, I'll keep an
open mind, and I'll wait for their answers, the answers from Dr.
Fauci or Dr. Gallo or Dr. Broder, and I have been waiting for a
year almost now. They didn't come yet, but maybe they're
preparing then.

So in terms of recommendation, I could only say we
could probably make tremendous savings in spending on the study
of this virus, about a billion dollars, and all of this money
could be made available for the study of AIDS, the disease that
we have to deal with.

Thank you.
[Applause. ]

[The prepared statement of Dr. Duesberg is included in
the Appendix. ]

DR. LILLY: Thank you, Dr. Duesberg. You have made your
usual and very charming presentation. Most of the scientific
community enjoys your iconoclasn.

I would like to speak briefly to the seven points that
you made on your slides. In so doing, I would like to recommend
that as I do every few years, it would perhaps be good if you
were to sit through our graduate course in animal virology. In
fact, all of your hypotheses are subject to exceptions. There
are indeed other viruses that do those things.

Your first point was that all known viruses are
biochemically active when they cause disease and you give polio
and hepatitis as an example. HIV apparently is not active.
Hepatitis virus, one of the ones you mentioned is indeed
biochemically active when it causes hepatitis, but it is not in
any traditional sense that we know, biochemically active when it
causes liver cancer, which it does, a long time after the initial
infection, after a very long latent period.

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DR. DUESBERG: Can I answer to this?
DR. LILLY: No, not yet.
(Laughter. ]

DR. DUESBERG: That's what I suspected.

{Laughter. ]
DR. LILLY: I didn't interrupt, you, did I?
DR. DUESBERG: No.

‘DR. LILLY: Your second point was that all known .
viruses when pathogenic infect and kill more cells than the host
can spare or replace. That is a difficult statement because in
fact we do recover to full normal health after many viral
infections. On the other hand, what you seem to be worried about
there is you are not satisfied with the explanations that people
have for why T-cells are killed. I don't think anybody is. That
is one of the things that we don't have an explanation for. I
don't think that means HIV is necessarily not the cause of AIDS.

In fact, most viral infections that I am aware of do
spare at least some cells among the target population in the
body.

Your third point was that all known viruses produce
primary viral disease after a short latent period of one to two
months. They act quickly or not at all. That contradicts the
review in which you first proposed that, in which you pointed out
that some people pay attention to the existence of a primary HIV
induced disease, which is a little bit like a brief and not
terribly noticeable case of mononucleosis. I'm perfectly willing
to accept that HIV is an acute virus in causing that disease and
perhaps in a sense like hepatitis, like herpes virus, then goes
to sleep in some sense for a long period of time and then is
capable of being reactivated.

Point number four is that all known viruses cause
disease in the absence of or prior to immunity. I would simply
like to point out that herpes lesions, the initial herpes ;
lesions probably occurs and certainly occurs in the absence of an
immune response. On the other hand, herpes, as most people who
have it, know that virus also becomes latent and is capable of
being reactivated later in the face of a very strong immune
response.

Point number five, HIV is a retrovirus and
retroviruses don't kill cells. That is indeed classically true.

83

 

 
 

 

Here again, your point there is we don't know the
mechanism whereby HIV is responsible for killing T-cells and I
agree with that point. We do not know that mechanism. I think
almost everybody is willing to agree that it might be secondary,
that the virus does not do it directly, it has an indirect
mechanism for doing it. It could even be a co-factor.

Point number six was no known virus discriminates
between men and women nor between heterosexuals and homosexuals.
We heard a great deal of testimony this morning about AIDS in
women. We have a great deal of dates about AIDS in Africa and
the Caribbean as a disease of heterosexuals. The fact that it
came into the United States and Europe largely in a founder
population is very simple and straight forward.

Your seventh one states that Koch's first postulate for
identifying a causative pathogen states that the pathogen must be
present in all cases of the disease. I can list a large number
of diseases for which I don't think you would take exception to
the cause, measles virus is widely accepted as the cause of
measles. Measles virus is not demonstrable in all cases of
measles. Syphilis, spirochete that is thought to cause
syphilis, is not isolatable in all cases of syphilis.

When we come to your conclusion that HIV is not the
cause of AIDS, you may be right. There is a slight possibility
that HIV is not the cause of AIDS. The evidence to date is in
fact circumstantial. But, there is an awful lot of it. I think
that even a small number of years before the institution of the
polio vaccine, there were still people who were saying that polio
virus was not the cause of poliomyelitis, that it was proven
essentially by the fact that people were able to make a vaccine
that actually protected, a polio virus-derived vaccine that
protected against the disease, poliomyelitis.

That was the final proof and probably the only real
proof that polio virus caused poliomyelitis. I think that will
undoubtedly stay true in the case of AIDS and the connection
between AIDS and HIV.

Dr. Duesberg, you and I have been very good friends and
I desperately hope that we will continue to be very good friends.
You have an awful lot of experience with retroviruses as
molecules in tissue culture. I wonder if you have very much
experience with viruses as pathogens in animals?

DR. DUESBERG: Is that a question?
DR. LILLY: Yes.

DR. DUESBERG: There was a monk in Czechoslovakia, a
Catholic monk. He had very little experience with genetics.

84

 

 
 

 

DR. LILLY: He had a lot of experience with peas, and
what he published about was peas.

DR. DUESBERG: He had an open mind, although he was a
Catholic monk. It seems to me that you are a teacher of
undergraduate virology. I am teaching graduate virology at
Berkeley. I think I could answer some of your questions if I had
the time.

DR. LILLY: I agree that this is a very poor forum for
this discussion. We are not going to satisfy it here and now. I
want to make the point that there are in fact people who like Dr.
Duesberg, do not have any personal stake in the answer to this
question, who disagree with his answer to it. I do not have a
personal stake in whether HIV causes AIDS or not. It seems to me
there is a great deal of evidence for it.

I would like to say also that I really appreciate Dr.
Duesberg's iconoclasm in that iconoclasm is very good for the
scientific community. It is very good for us to be forced to
re-examine the fundamental principles, the principles that we
think are fundamental. They may not be fundamental in fact.

For that reason, I rather regret that this has come to
be a forum, a very superficial one, we will not settle the
question today for this, and I should say one of the reasons I
regret is because I heard Dr. Duesberg make a presentation a
couple of weeks ago to a group of people, to an audience in which
a large percentage of the audience consisted of people who were
HIV infected and some of whom were asymptomatic, some of whom
were symptomatic.

The person who sat down beside me, who I came to know
very shortly, was a man who had said he had just before been
diagnosed. I sat and listened to Dr. Duesberg through the filter
of my conversation with this young man who was very upset. I
realized that this young man was not understanding the points
that Dr. Duesberg was making. He was not a scientist. What he
was hearing was the experts don't know anything, they are fakes,
they are frauds, you are on your own, and that was devastating
information.

For that reason, I regret that it has become a public
question, although I realize that Dr. Duesberg did not make it
so.

DR. DUESBERG: I would like to address this one point.
You said yourself that I may even be right and the evidence is
circumstantial. In the meantime, people are taking AZT, which is
clearly a killer. It is one of the most toxic --

85

 

 
 

 

DR. LILLY: You don't seem to want to let me finish
because I had a question to ask you. I was going to end ny
presentation with a question to you.

Since HIV is "bullshit", what should the scientific
community be doing?

DR. DUESBERG: The exact quote is "cock and horse
shit." That is what the nation's leading AIDS researcher said

that in Spin Magazine.

With regard to AZT, even if the virus were the cause,
AZT could be efficient if the virus were actively making DNA at
the time when this drug is delivered, but there is no evidence
for that. In fact, even Dr. Gallo and other laboratories that
cost about $1 million a month to run are unable to detect DNA
synthesis at the time AZT therapy is used. In the face of what
you just said, the evidence is circumstantial, I wonder how good
a public health policy that really is.

DR. LILLY: Do you think measles virus causes measles?
DR. DUESBERG: Yes.
DR. LILLY: Dr. Lee?

SPEAKER FROM THE FLOOR: I would like to address
something.

DR. LILLY: I'm sorry. We have a very tight schedule.
We are already over time for this session. We are going to have
to maintain the protocol for these hearings. It is impossible
for us to be able to entertain comments from the floor. We would
be pleased to receive anything in writing to the Commission. We
are serious about taking them into account.

Dr. Lee?

DR. LEE: Dr. Solomon, I commend you for your early
reports on the VietNam vets and drug abuse. I take care of a
number of those people who have ended up being HTLV positive with
very aggressive lymphomas and they are a particularly sympathetic
group.

I wanted to ask you a question about stress. I'm sure
you don't have an answer but I would like to hear your thoughts.
Stress is with all of us. When we look at stress today in the
cancer world, we never could find anyone who didn't have stress.
At least it was my theory that the best way to deal with stress
is to deal with the cause of it. As long as you don't go back
and deal with the cause of it, you are constantly dealing with
the sympton.

86

 

 
 

 

When you are trying to get a handle on stress, have you
found any way to measure it?

DR. SOLOMON: I don't like the word "stress" because
stress refers to something external. I much prefer the term
"distress." There are various forms of emotional distress, which
result from external events not being adequately coped with or
old issues within the person, not having been resolved. These
can lead to emotional distress of various forms. All distress
isn't the same, just as the immune system is not uniform and
isn't uniformly suppressed or enhanced.

In my research and in that of others, there are a
number of studies to show that different forms of stress or
distress can affect immunity in different ways. I would say that
in humans, depression, particularly helplessness and
powerlessness and feelings of despair and grief, which certainly
are relevant to the HIV epidemic, are particularly damaging to
immune function. Of course, how this is related to clinical
illness is sometimes open to question.

In humans, there are studies to show that bereavement,
depression, even examination stress, are all reflected in some
aspects of immune function and that certain things such as social
support can buffer the effects of those stresses.

I do prefer to look at how the person deals with
stress, and how it is affecting the individual, rather than what
the event is.

DR. LEE: There is no question that it affects disease
adversely, but we all have it at high levels almost daily.
Really, if somebody in this audience were to stand up and say
they are they without stress, I would love to meet that person
and talk to then.

But the question is, can you measure the stress so that
it is meaningful to us?

DR. SOLOMON: Yes. I have been impressed that
psychological measurement really isn't that much less accurate
than immunologic measurement and that we indeed to have tests for
anxiety, for depression, for a variety of emotional states and
traits and for coping that indeed can be quantified and
correlated with physiological measures and clinical status.

DR. LEE: Thank you.
DR. LILLY: Dr. SerVaas?

DR. SERVAAS: I want to thank the panel, particularly
Dr. Levy. -

87

 

 
 

You are interested in keeping people with AIDS alive
six years longer and there are so many differences of opinion
among infectious disease experts on what is and is not
immunosuppressive and how immunosuppressive is alcohol and how
much, since you are talking about diet, how much alcohol is too
much in order to maximize longevity.

I wondered if you could tell us in addition to
nutrition what you know about smoking and taking aspirin and all
the other things that we now advise the HIV positive individuals
to do or not to do.

DR. LEVY: As far as chronic effects, I think alcohol
doesn't have a particular effect on immunity until you get into
an advanced alcoholic state and already have liver disease.
Acutely, you do have diminished immune responses, perhaps for 24
hours after heavy drinking, you may have diminished immune
responses. I think it is extrapolating but one would imagine
that you are more vulnerable during that 24 hours and you are
allowing perhaps a step up in the advance of this virus which
does progress and have a very slow advance.

Although there is not hard evidence, I'd’ say it would
be advisable for people to cut down on alcohol consumption.

DR. SERVAAS: How much?

DR. LEVY: I would have to do some research. I would
have to look at that. Apparently, with breast cancer, there is a
suggestion that as little as one drink a day is a risk factor.
Something quite modest might be something to look into.

As far as smoking, heavy smoking is thought to impair
immunity upwards of two packs a day over an extended period of
time, but I believe moderate smoking hasn't been shown to have
much of an effect.

DR. SOLOMON: I might add that heroin is extremely
immunosuppressive because of its intermittent use, unlike
methadone, which is a steady dose, and which does not appear over
a long period of time to be immunosuppressive. Thus, it is much
more adaptive for a person to be on methadone maintenance than to
be taking other forms of exogenous opiates, like heroin. Drug
effects on immunity vary. I am not cocaine advocate, and I think
cocaine abuse might be a worse epidemic even than heroin. Its
effect on immunity, however, is less than heroin. Again, it is
specific to the particular drug.

DR. SERVAAS: Thank you.

DR. LILLY: Mr. Creedon?

88

 

 
 

 

' MR. CREEDON: I am very interested in the nutritional
and the other psycho-social factors involved in this disease. I
notice that Mr. Hannan and Dr. Sonnabend are still here, and I
would hope if it were possible in your clinical trials to include
these factors. I think it could have significant benefits, not
only as the Admiral has said on a number of occasions that some
of the things that we are learning and some of the things that
are being brought to our attention could be useful not only in
the war on AIDS but looking forward to other types of medical
problems.

I think that if anything, the pyscho-social aspects and
the nutritional aspects may have been neglected and we might have
a basis here for establishing an approach to scientific inquiry
that would be the start of a movement that could be significant.

L

CHAIRMAN WATKINS: I would agree with that. I think it
would be very important if we could have some kind of a concept
on how this might be reflected, how this might be picked up. It
is the kind of things we would like to note in our report. We
have already put emphasis on psycho-social factors and we don't
know enough about the nutritional impact. We have asked many
questions to witnesses who have come before us about the kinds of
things that Dr. Levy talked about and haven't received very
Satisfactory answers, perhaps we need to know a lot more.

MR. CREEDON: Maybe they could work with Mr. Hannan.

CHAIRMAN WATKINS: Mr. Hannan, could you indicate
whether you would be willing to at least receive representation
from these two to see how they might have some kind of an impact
on trials as an adjunct to what you are already doing.

' MR. HANNAN: Of course.

MR. CREEDON: I would like to ask Dr. Duesberg one
question. Recognizing the state of scientific knowledge or
reported Knowledge or whatever, what recommendations if any would
you have for the Commission? You have a question, you are a
respected scientist, a number of the witnesses that appeared
before us today, including Dr. Sonnabend, and yesterday,
expressed similar doubts about whether HIV is the culprit, and
yet the whole scientific community is lined up on the other side.

What do we as a Commission do? Do we ignore you or do
we suggest that a certain amount be Spent on other research?
What do we do?

DR. DUESBERG: You are the only one who hasn't done
that so far. You have not ignored me. You have asked me to
come. We have to find the cause of AIDS, and I think Frank Lilly
would be satisfied if we found the true cause. I think we would

89

 

 
 

 

have to have better reporting to do that. We are told that
something is antibody positive in any of a number of diseases,
that I, admittedly, not being an M.D., cannot possibly reconcile
from my narrow perspective of a molecular biologist, as being
caused by one agent. In fact, whoever coined the word "AIDS"
showed more wisdom, because AIDS means acquired immunodeficiency
syndrome. "Acquired" doesn't mean infectious and "syndrome"
doesn't mean a disease entity. It is a collection of old
diseases.

There is dementia, diarrhea, weight loss, pneumonia,
pneumocystis carinii, Kaposi's sarcoma, lymphoma, these things
couldn't possibly all be caused by one agent. They couldn't even
be explained on the platform of immunodeficiency.

If you are immunodeficient, at least from what I know,
you don't become stupid. You don't develop dementia. There are
models like that, people born without immune systems and kept
alive in sterile "bubbles," they are not stupid. There is a
mouse model for that, which was specifically developed to test
whether immunodeficiency increases cancer incidence. It doesn't.
They do not develop any more tumors than any other laboratory
mice. One of the key symptoms of the disease is Kaposi's sarcoma
and lymphoma and dementia now.

Maybe antibody is a good marker to know about but we
should not just call it AIDS. We need to know who gets dementia,
who gets Kaposi's sarcoma, who gets lymphoma and who has diarrhea
and who has just weight loss.

DR. SOLOMON: There are many similarities between the
immune system and the central nervous system. We now know there
are a number of similarities in so-called messenger substances
that communicate between nervous cells and lymphokines or
cytokines that communicate in the immune system. This is the
basis of Candace Pert's work, in which she has basically in her
Peptide T research, tried to develop a treatment for AIDS and has
tried to block a receptor site for a neuro peptide through which
the virus may enter the cell.

We know there are similarities. We know there is
involvement in the brain of macrophages and some neurons also
have the T4 receptor site. When Dr. Duesberg says how could the
virus cause dementia, there are a number of ways the virus could
cause dementia because other viruses, such as measles virus,
affect both lymphocytes and the nervous system.

MR. CREEDON: Thank you.

DR. LILLY: Dr. Walsh?

90

 

 
 

 

DR. WALSH: I don't have a question; I do have a
comment, however. I would first of all reassure any of you who
may have been in doubt that the compelling evidence of the cause
of AIDS I think is well known and also the fact that continuing
research is going on and will continue to go on -- and that is
how we are finding also the mutants and the various strains.

One thing I would hope, and Dr. Duesberg certainly is
entitled to his theory and his opinion, but I would hope that you
would press your theory within the scientific circles and not
carry this uncertainty to the public in order to sensationalize
something that isn't worth -- at this point -- talking about.

By that I mean, whether you are invited now -- not only
on "Good Morning, America" but on several other shows, to have
the scientific integrity to resist until you have something more
substantial to say, rather than causing the dismay or despair
among those people who are susceptible to the depths that they
can be thrust by uncertainty. ;

As Dr. Lilly has said, you are a respected scientist
and I think you keep your theories in scientific discussion until
they are proven; don't confuse the public; don't confuse these
poor people who are suffering with this disease. It is very,
very unprofessional.

VOICE FROM THE AUDIENCE: It's been a year and they
haven't answered him. One year ago. he wrote it, and they
haven't answered him. Where is the scientific community's
response to Dr. Duesberg? You should be ashamed of yourself for
saying something like that, Dr. Walsh.

DR. LILLY: Dr. Crenshaw?

DR. CRENSHAW: What I would like to share or express is
that while I find it very difficult as you heard earlier to
accept any theory based on a distinction of this virus between
whatever label someone happens to carry -- their sex or their
sexual orientation -- I don't agree with that. I think that this
is everyone's disease and we have to stop thinking of it as such
a selective virus.

I have to say that I think that it is really important
that we negotiate that fine line between a catechism of AIDS
where no unpopular theories or outside concepts are entertained,
and getting diverted or going astray on issues that mislead us in
some way. We don't know everything about AIDS, I don't think, so
I think we do need to keep that aliquot of open mind and if Dr.
Duesberg's theories have merit, the evidence will accumulate and
accrue.

91

 

 
 

 

On the other hand, it is difficult because we are
trying so hard to get all of the information accessed and all of
the answers, and there are majority opinions and majority
reports, so I would just urge for a balance where we can listen,
have an open mind -- but not toss out what we have achieved.

DR. LILLY: Ms. Pullen?

MS. PULLEN: Dr. Duesberg, if you believe that because
of the things you say about viruses AZT could not be working to
arrest this virus in any way, how do you explain that in many
cases it appears that AZT in some way has prolonged life and
improved health of individuals who are taking it, at least for a
period of time?

DR. DUESBERG: That is not for me to say. I can only
say, on the basis of antiviral therapy, it cannot work. If it
helps, all the better for Dr. Broder. I would like to see the
data. What I have seen hasn't convinced me of what you are
saying, but maybe he has those data. I haven't seen them. But
it can't hurt a virus that doesn't make any DNA, that is for
sure.

And I know one thing also for sure. This stuff is used
for sequencing, as Dr. Broder proudly advertised yesterday. He
said he finds it aesthetically pleasing that he is sequencing DNA
in human bodies. What he is saying is he is chain terminating
and killing cells. That he does very successfully and I
understand that people need red cells, transfusions -- they need
other transfusions because it is killing cells. It is developed
for chemotherapy: it is a killer. That is what we know.

It may work like chicken soup; I am not an M.D. There
is a mystique. I don't know how aspirin works, I don't know how
cocaine works and I don't know how AZT might work in addition to
what it does for sure: namely killing cells that incorporate
that drug. That is what it is designed for.

DR. LILLY: Admiral Watkins will close out the
session.

CHAIRMAN WATKINS: To Dr. Levy and Solomon, could you
give us any idea of how effective CDC or NIH has been to date in
collecting any data on co-factors and -- that is one question --
and the other one is, what would you -- looking into the
government agencies, who do you think would be the most
effective, and who should perhaps we look at to charge with
additional research on co-factors?

Could either one of you or both of you respond to those
two questions?

92

 

 
 

DR. SOLOMON: I would like to comment perhaps in
addition to Dr. Levy about this. The situation has improved
recently. Initially, NIH would not look at anything psycho-
social as related to its biomedical and immunological studies.
And in contrast, NIMH wouldn't fund anything biological. For
example, our attempts to get money to do very expensive
immunological testing in conjunction with our psychosocial
studies work were consistently thrown out by NIMH.

This is now changing, thank goodness. But I think that
perhaps this separation of institutes between NIH and NIMH has
been a problem and that there needs to be coordination among the
various institutes: Infectious Disease, CDC, NIMH and perhaps a
greater coordination could be arranged among these so that a more
integrated approach to research could take place.

CHAIRMAN WATKINS: Thank you. Dr. Levy?

DR. LEVY: I would agree with Dr. Solomon's comments.
Recently ADAMHA has begun to fund co-factor studies, although
they are just beginning and I think there are not that many yet
funded. They are interested in psycho-social influences,
including drug and alcohol, as co-factors in the development of
AIDS.

I think if you throw in nutrition, the division that
Dr. Solomon was talking about between NIH and NIMH becomes more
of a problem, because then I really don't know -- I have thought
of this -- where would one submit such a grant? It is hard to
say.

The study sections are not set up with the expertise to
properly evaluate such studies.

CHAIRMAN WATKINS: Would the two of you be willing to
team up and send me a letter, a specific letter saying what you
think is needed and from your vantage point, how you think that
collaborative effort could be enhanced and what you would do to
enhance it, because I think it keeps coming up in these
discussions and it keeps getting sloughed off, perhaps without
any conclusion. I would like to try to put some steam into that
engine and see what we can do to bring about a much better
dialogue on this particular subject.

Thank you, very much, panel members for being here. We
will go to the next panel now, and I would like to turn over the
chair now to Dr. Theresa Crenshaw, to deal with the entire
session this afternoon on behavioral research.

So, Dr. Crenshaw, if you will take the chair, please,
and our first witness will be Dr. Thomas Coates for a very brief

93

 

 

 

 
 

 

introduction before we go on to Dr. June Reinisch, Dr. Voeller
and Dr. Gagnon.

Behavioral Research

 

DR. CRENSHAW: I would like to begin the hearings on
behavior and sexuality, so if those of you who are going to stay
to hear those hearings could gather, we will get started.

We have such a very brief period of time to deal with
the subject. I know it has been a long day and it will be a
little bit longer, but I would like to very briefly create a
setting here for you wherein a disease that is primarily
transmitted through sexual behavior we need to draw on experts
who have a long history and reputation in understanding the
complexities of human sexuality to put many of the things that we
need to know in order to act responsibly and plan the future into
perspective.

The first is going to give us an overview of
behavioral research and the possibilities in modifying sexual
behavior -- Dr. Thomas Coates, who is Co-Director of the Center
for AIDS Prevention Studies at UCSF.

Thank you, Dr. Coates.
DR. COATES: Thank you, Dr. Crenshaw.

First, let me introduce myself and say a few words
about my background, because I think it is very important for the
points I am going to make. I ama psychologist. I am an
associate professor in the Department of Medicine at the
University of California, San Francisco. I direct the Behavioral
Medicine Program in the Department of Medicine there. I am also
on the attending medical staff of the University of California
hospital. I believe that those Capacities straddle, sometimes
uncomfortably as straddling always is, the worlds between the
behavioral and the biomedical sciences.

I would like to actually make two general points in
this opening session, and I was asked to make some statements
about the role of behavioral research in health problems
generally and the kinds of contributions that behavioral research
can make and the kinds of questions that can be answered. I
would like to do that.

But I would like to precede that by saying that
ironically -- you know, your comments are very well taken -- AIDS
is fundamentally not a viral disease. AIDS is fundamentally a
behavioral disease. The modes of transmission have been well

94

 

 

 
 

described and there is some uncertainty about other specific
modes, but the major modes are well known.

Yet it is ironic that we continue to spend precious
little money on prevention and especially on prevention
research.

Let me draw some comparisons. The National Heart, Lung
and Blood Institute, which is where I have received my funding
for the last 12 years I have been involved in cardiovascular
disease prevention, an enterprise that has paid off well. All
one needs to do is look at the dramatic fall in deaths and
disability due to cardiovascular disease over the last 20 years
to realize that this research has paid off.

The NHLBI spends $132 million annually on prevention
research and on behavioral research.

The National Institute of Mental Health's current
budget for AIDS prevention research is $5 million.

The total PHS budget that was requested for AIDS
research, the original PHS budget that was requested for AIDS
research in 1988, was on the order of $900 million -- $412
million for research, including only $28,000 to ADAMHA. In
essence, we have the ratio between traditional biomedical and
behavioral research being 4:1, and within the prevention arena,
again the ratio being about 10:1 between programs and research.

It is vital that we support more research in this area
and it is vital that this be placed at the NIMH and I think it is
vital that this Commission make a strong statement to ADAMHA that
they need to support behavioral research.

Now what can behavioral research do? Now that we want
to support it, does it have any place?

[Slide. ]

I'd like to use this little schema to talk about the
relationship between the relationship between biomedical and
behavioral research and to point out the major questions that are
relevant here. I like it because it divides the world into four
boxes and it is always simpler when you can deal with four boxes
instead of the complexity of reality as it is. Nonetheless I
think it is useful.

Independent and Dependent Variables, Biomedical and
Psychosocial Variables -- the upper left hand quadrant being the
domain of the traditional biomedical sciences; that is, the
effort is to find the lesion or the agent that produces a

95

 

 
 

 

biological outcome and somehow to take care of that agent either
through a procedure or through a chemical.

The lower right hand quadrant defines the domain of the
traditional behavioral sciences. That is, we are interested in
outcomes in terms of cognition, in terms of affect, in terms of
behavior and we want to know what other psychosocial variables
are related to those conditions.

The interesting arenas are on the other diagonal; that
is, moving first to the lower left hand quadrant, we are asking
about the influence of biomedical variable on psychosocial
variables. Here is where behavioral research becomes quite
important. We can ask this in a number of dimensions. What is
the influence of the virus either in a primary way or due to
secondary infection on people's cognition, on their behavior, on
their affect? Can we, in fact, through various biological means
modify people's cognition, behavior and affect?

It is probably the one arena in which modern
psychiatry has advanced remarkably over the last 20 years, and
that is by finding better ways to intervene chemically to modify
major problems such as schizophrenia and the major affective
disorders.

The other arena is the arena you have just been
considering, and that is, "Do psycho-social variables in fact
influence the biological variables?" We can ask about that in
two different ways. We can ask about behaviors that are
directly related to disease, behaviors such as smoking tobacco,
ingesting drugs, behavior such as nutrition and exercise and
certain kinds of sexual behaviors that are related to certain
kind of biological outcomes because they introduce the disease
process or make the disease process more rapidly. We can also
ask about affective states which influences biological outcomes
and ask questions about the potential of intervening on those
psycho-social states to modify the biological outcomes.

Now the problem is, when we get to the area of AIDS
research and we get to the area of sexual behavior research and
to IV drug behavior research, we want to somehow put these in a
special category. I will submit, and my testimony later I think
will provide evidence, to submit that these behaviors are under
the control of variables that influence many other kinds of
behaviors. So therefore the objective becomes one of describing
those determinants and deciding if we can intervene on those
determinants.

Let me go back to an important model, and that is the
important model used by the National Heart, Lung and Blood
Institute and the important model used by the National Cancer
Institute in its War on Cancer.

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Again, in both arenas there has been a long, 10-20 year
history where the progression has been from describing the range
of behaviors related to those diseases in the population and in
various sub-populations to developing studies that will describe
the determinants of those behaviors in various populations to
describing, to developing intervention studies that will
hopefully modify those behaviors and look at disease outcomes as
a result.

Let me make real explicit two biases that pervade the
scientific world that inhibit the progression of this kind of
research. I think they are important biases. They are
important scientific biases which have inhibited an effective
response to the AIDS epidemic.

The first is that somehow behavioral research is a poor
second cousin to the so-called "hard sciences." It has been very
interesting for me in my cardiovascular research history and now
in my AIDS research history to venture into other people's
sciences and to realize that they have the same problems that my
sciences do. The variability around a single measure of immune
function or immune status is I think well known, just as the
variability of a single blood pressure measurement is well known.

I would submit that the behavioral sciences can be just
as "hard" and as theoretically driven as the biomedical sciences.

The second point I would submit is that the tradition
in our academic institutions is that so-called "basic research"
that is translated to mean "laboratory research" somehow has more
credibility and believability than the clinical field trial. As
anyone knows, both are need to carry on an adequate and to
develop an adequate knowledge base.

The last comment that I would make with regard to this
issue, and it's not intended necessarily as a criticism but I
think just as an observation. I think that this committee also
operates in a culture that shares the norms of the larger culture
and I think it is interesting in a three day hearing that this
session is coming at the end. I think that tells it all. Thank
you. : .

DR. CRENSHAW: Thank you very much.

What we might do with the next few minutes is ask
questions before the next panel takes place. We just have a few
and bear in mind that Dr. Coates will be available later for
additional testimony, additional questions.

Dr. SerVaas?

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DR. SERVAAS: Do we have your testimony in writing?

DR. COATES: I was told that I didn't need to prepare
this particular opening segment of testimony in writing. My
testimony later in the hearing will be in writing and it does
make some of these same points.

DR. SERVAAS: You will be testifying again?

DR. COATES: I will be testifying on behavior change,
particularly in gay and bisexual populations, the reasons for
those behavior changes and a program of research that I think is
needed at the NIH to promote that activity.

DR. SERVAAS: I'm sorry, I haven't done my homework,
but I am just curious. You are a cardiovascular researcher,
clinician?

DR. COATES: I am a behavioral scientist; I ama
psychologist by training. My appointment is in medicine. I run
a subspecialty clinic in the Department of Medicine. My research
prior to AIDS was done in cardiovascular disease prevention and,
since 1983, I devote a considerable energy to AIDS prevention --
which I think is the primary research agenda in AIDS.

DR. SERVAAS: Well, I am so happy you are here because
I can't agree with you more that we should be spending a bigger
part of our budget on prevention. Certainly if we can do for
AIDS what we did in cardiovascular work, that is an excellent
point. Thank you.

DR. CRENSHAW: Mr. Creedon?
MR. CREEDON: No questions.

DR. CRENSHAW: Dr. Walsh?

DR. WALSH: Dr. Coates, I -- just as you, I am somewhat
astonished that in all of our hearings we have heard relatively
little about behavioral research despite the fact that we have
had pleas from some behavioral scientists early on.

But in one of our earlier hearings, the Director of the
National Institute for Mental Health appeared before us and,
while it was not earmarked money per se, he did make the
statement that at least in the area of drug abuse, which
astonished me, that he had not had sufficient requests to use the
funds he already had.

This didn't make any sense to me at all.

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I wondered whether there is such a vigorous earmarking
between behavioral research money just for AIDS or whether the
Institute of Mental Health funding could be used, since so much
of it is involved with behavior in drug use and so on. Do you
have any awareness of whether that line is so rigidly drawn at
NIMH?

DR. COATES: You mean -- I am not sure I understand
your question.

DR. WALSH: The funding that would be available --
like if they have given only $5 million for behavioral research
studies in AIDS --

DR. COATES: Annually.
DR. WALSH: That is a drop in the bucket.
DR. COATES: Exactly.

DR. WALSH: But if they have given $160 million or
whatever it is for behavioral research in substance abuse, is
there any way we can get that funding combined so that more could
be directed towards AIDS behavioral sciences?

DR. COATES: In AIDS prevention, yes.
DR. WALSH: Actually, AIDS-related diseases.

DR. COATES: In AIDS-related diseases as well. There
are two problems here. One is my look at the portfolio of
research for the National Institute on Drug Abuse lists
approximately nine studies aimed at various populations for AIDS
risk reduction and then there are community demonstration
projects in six cities.

I think that is a drop in the bucket as well.

The difficulty also comes in the structure of the NIH
and ADAMHA and it is somehow divided by body parts and diseases
and doesn't seem to have a central nervous system that allows it
to communicate among its body parts and diseases. I think there
is incredible need for better coordination.

As an example, research is vitally needed on the
intersection of IV drug use and sexual behavior, which is to be a
major mode of transmission. It seems like that is a perfect
point of intersection for cooperation between NIDA and NIMH.

As another example, and as I am’you will find out from
the next panel, research in sexual behavior, just describing it
in the population as well as understanding its determinants for

99

 

 

 

 
 

 

various sub-populations does not reside within the purview of
any one institute. The National Institute of Child Health and
Human Development is interested in adolescents and young adults
principally from a fertility perspective, which is important but
no one has the mandate to develop and implement a program of
sexual behavior research. I think there should be that.

DR. WALSH: This concerns us a great deal because you
know we keep talking about the greatest weapon we have is
education and then we talk constantly about counselling and yet
the answer to all of that rests in behavior research.

DR. COATES: Indeed.

DR. WALSH: In how you find the answers. I think it
would be very helpful to us when you do have your written
submission that you give us some very good specifics.

DR. COATES: Indeed. I will.

DR. WALSH: I think we can have an influence on that, I
really do.

DR. COATES: Let me give another example that I think
this committee can address. That is, a structural problem in the
relationship between the NIMH and ADAMHA. When NIH coordinating
committees are set up, frequently they don't involve folks from
ADAMHA. If ADAMHA is invited there, they are invited as
observers only. I think that is not the way. Again, it isa
reflection of the biomedical view of behavioral sciences.

Ironically, however, the biomedical scientists are
saying, "This is a behavioral problem." Even if you have got an

efficacious agent -- and I think we have got examples -- we know
that penicillin works for syphilis and gonorrhea except for
penicillin-resistant gonorrhea -- delivering it is still a

problem. We know that we have an effective vaccine for hepatitis.
Delivering it is still a problem. So the behavioral and the
biomedical really needs to be combined. Condom efficacy may not
be a problem. Compliance with techniques to make condoms
effective may be a problen.

DR. WALSH: Well, since that is our prime weapon for
the next 10 years, based on everything we have heard so far, it
seems absolutely backwards to me. We will need your help.

DR. COATES: Indeed. Thank you.

DR. CRENSHAW: thank you very much, Dr. Coates. We

look forward to hearing from you again a little later. I
would appreciate if the next panel would come and join us.

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Sexual Behavior

DR. CRENSHAW: We will be hearing first from Dr. June
Reinisch, Director at the Kinsey Institute, and after that from
.Dr. Bruce Voeller, from the Mariposa Research Foundation, and
then from Dr. John Gagnon from Princeton University.

I want to first apologize to all of you for the brevity
that you are faced with during this testimony and I hope that it
turns out to be just a preview of an expanded, in- depth look
into all of the issues that I know you will just touch on today.

So because of the brevity, let me not add to it by
taking any more of your time. We look forward to your comments.

DR. REINISCH: Thank you, Dr. Crenshaw.

My name is Dr. June Reinisch and I am Director of the
Kinsey Institute for Research in Sex, Gender and Reproduction at
Indiana University. I am also a professor in the Departments of
Psychology and Psychiatry. In addition, my staff and I author an
internationally syndicated column which appears across the United
States and in eleven countries around the world. The column is
based on current research data and provides readers with facts,
not advice.

First, as this is the first time that the testimony on
sex behavior has been brought before the commission, I want to
express my deep concern for the lack of adequate time to present
information on this most sensitive area of human concern, which
is essential to the control of the spread of the AIDS virus. It
is impossible to make comprehensible recommendations or propose
model solutions without providing the background information on
the history of sex research and what we know and don't know. I
hope that additional sessions of the committee in the future will
be devoted to the complexities of these crucial issues and I hope
that you will permit me today to take a little additional time
from my question and answer period to speak so I can provide at
least a minimum of these kind of data. I want to share data with
you, new data and old data.

Sex research, that is who is doing what, with whom, how
often, and under what circumstances, and information on the
attitudes which related to these behaviors will provide the
essential foundation upon which effective programs of behavior
chance, so necessary to stemming the tide of the AIDS epidemic,
must be built.

This yet-to-be-collected information will also provide
crucial information for conducting research on the efficacy of
barrier methods to block infection with HIV and assist in the

101

 

 
 

 

identification of appropriate subjects for such biomedical
solutions as testing vaccine.

The sexual behaviors that place individuals at risk for
infection by the AIDS virus are not new. Nor are they limited to
the cultural post-sexual revolution America. Despite the beliefs
of some that behaviors related to HIV transmission are the
product of Western civilization in the second half of the
Twentieth Century, even a cursory examination of the
archeological and ethnographic record reveals art, artifacts,
literature and ephemera which reflect the ubiquitous panhistoric
omnicultural nature of the behaviors implicated in the
transmission of the AIDS virus.

Much of the very limited research on human sex behavior
has been plagued by a number of serious limitations, resulting in
most cases from a general lack of both public and private
research support for scientific investigation into human
sexuality.

Despite these shortcomings, I have selected among the
best small, usually government or foundation funded scientific
studies and the large, usually commercially supported surveys to
gain at least a limited perspective on the patterns of sexual
behavior, but only in white, middle class, relatively educated
Americans.

Based on these data, some preliminary insight can be
gained into the prevalence of risk-related behavior, such as
heterosexual and homosexual anal intercourse, fellatio,
cunnilingus, extra-marital contact, group sex, bisexuality and
the use of prostitutes.

I will be referring to data from 16 studies, beginning
with the original Kinsey research.

I must emphasize here that very rough estimates from
these data can only be made to white, middle-class, usually urban
Americans between 20 and 45 years of age and not to the numerous
ethnic, racial, social and sexual orientation and age groups
which comprise the United States.

Secondly, all of these data are flawed. There has
never been a scientifically designed, face-to-face interview
study of the American population. Had there been such publicly
funded research describing the major subgroups in our society we
would be much closer to behavioral control of this epidemic than
we are today.

(Slide. ]

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I think the prevalence of monogamy in our society is
one of the issues that we are all concerned with, since we know
that the number of partners has something to do with the
transmission of this virus.

Here you see a number of studies on the extramarital
affairs of husbands, and as a conservative estimate we can say
that approximately 40 percent of the American population who is
married and who is male has had at least one extramarital affair.

You will see we have considerably more information on
females than males because of the surveys conducted regularly by
women's magazines like Redbook, Ladies Home Journal, and

Cosmopolitan.

 

One of the enduring beliefs in our culture is that
women are much less likely to be involved in extramarital sexual
interactions. Although it does appear that husbands ar more
likely to participate in extramarital affairs, wives are not far
behind.

(Slide. ]

Our conservative estimate from the data that are
available: about 30 percent.

Why are the bars so uneven? It indicates the variation
in methodologies used, the biased or small samples involved, the
different levels of scientific expertise involved in the designs
of these studies. Nevertheless, even if the most conservative
estimate from the 1940s are taken -- in this case 20 percent of
wives involved in extramarital affairs -- it is clear that we are
dealing with a significant portion of our population.

[Slide. ]

The next behavior about which we have some but by no
means adequate information is anal intercourse, the behavior most
implicated in the sexual transmission of AIDS in this country.
This is a behavior which most people believe is not common in the
heterosexual community.

[Slide. ]

Here, from a few studies on heterosexual males, in
heterosexual anal intercourse we have a conservative estimate of
20 percent, which you will see in the next slide probably is too
conservative because when we look at the data on women, we find
out that conservatively 35 percent of women have had at least one
experience with heterosexual anal intercourse.

(Slide. ]

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Sexual prostitutes is also been suggested as an avenue
of transmission of the virus into the general population --
heterosexual population. Prostitutes appear to be infected not
by their customers but via shared needles during IV drug use and
perhaps more importantly from sexual behavior with their IV drug
using husbands and lovers.

Our conservative estimate of use of women prostitutes
by the general population is 35 percent.

We are all concerned about the question of the spread
of the virus from groups with a high prevalence of the virus to
the larger "heterosexual" population. Comprehensive descriptions
of sex behavior in all segments of our society will provide
answers to these questions. We don't have the answers.

We all know about IV drug users and the gay community
and would like to believe that the majority of our population is
isolated and thus safe from the at risk groups. The data that I
am going to show you now, present to you now, show ale this is
really not true.

[Slide. ]

If you ask homosexual men have they ever had
heterosexual intercourse, two-thirds to three-quarters of
homosexual men report from various studies over time that they
have had sexual intercourse at least one time with women and
one-quarter to one-third of homosexual men report that they have
been married for some time in their lives.

When we look at the general male population, we see
that approximately one-third of the general male, American
population has had at least one sexual encounter with another
male following puberty. When we ask gay males about their
interactions with married men, Kinsey showed as others have that
70 percent of gay white males have had sex with a married man at
least once and 20 percent of these have had six or more married
male partners. We are not isolated from each other.

A recent Institute study of cross orientation sexual
behavior in lesbian women sheds additional light on the
inaccuracy of sexual orientation labels for predicting actual
behavior.

(Slide. ]
In a sample of 300, nearly 300 lesbian women from
around the United States, nearly three-quarters who currently

label themselves as lesbians, had at some time previously labeled
themselves as heterosexual or bisexual. Approximately 20 percent

104

 

 
 

 

had been married or co-habitated with a man. One~-quarter. .
reported that they had always labeled themselves as lesbian.

Behavior across sexual orientation boundaries in terms
of intercourse with men -- these supposedly safe lesbian women
who are supposedly the lowest risk group in our culture,
approximately three-quarters of lesbian women had sex with a man
since age 18. One-half of the currently labeled lesbian women
had had sex with a man since 1980; that is our banner year for
the beginning of the AIDS virus in large amounts in this country.
One-quarter of the women who reported that they had labeled
themselves as lesbians had had sex with a man always labeled
themselves as lesbian, and that is the middle pie, had had sex
with a man since 1980 and one-third of all the lesbian women
reported that at least one of their male sexual partners was a
man who had sexual experience with other men. In most cases they
were men who labeled themselves as "homosexual."

[Slide. ]

Depending on whether a woman knew she had had a male
sex partner who was what we would like to call "behaviorally
bisexual," since even if they called themselves "homosexual" they
are obviously having sex with women, we asked was there any
difference in the frequency of high risk sexual behaviors,
depending on what kind of a partner you had -- at least the
partners you knew about. The left bar -- 41 percent of the
population from the general population surveyed in various ways
since 1974 reported having had anal intercourse at least once.
There is no information as to their knowledge of their male
partners' sexual interactions with other males, but from our
experience it is unlikely that many would know, since American
men and women talk very little about sex, and homosexual behavior
is a particularly taboo subject.

Of lesbian women whose male partners as far as they
knew were only heterosexual -- that is the middle bar -- 24
percent had experienced anal intercourse, while of lesbian women
who knew at least one of their male partners had homosexual
contacts, 45 had anal intercourse. Other studies are now showing
us as well that women who have sex with behaviorally bisexual
partners are more likely to have anal intercourse. We also expect
that lesbian women are more likely to know of their male
partner's homosexual contacts than are heterosexual women.

Another way we think communities are safe from
infection is through geography.

(Slide. ]

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In my last slide -- I think Americans believe that if
we are separated by distance from the cities identified as having
high risk of infection then we are safe. We asked our subjects
about trips to New York, San Francisco, Los Angeles, Houston,
Washington, D.C., Miami, Chicago, Newark, Philadelphia or Dallas
~~ the ten top CDC cities for AIDS infection since 1980 -- had
they visited and had they had sex with a partner from that city
at that time. On the right bar, 29 percent said they had had sex
with a resident of one of the ten high risk cities. Eleven
percent said they had sexual contact with -- remember these are
lesbian -- with a male resident. At the right bar, of these
lesbians or bisexual women who had sexual contact with a male in
one of these cities, for 49.5 percent it was a first contact with
a new sexual partner. Again, this is since 1980 -- and remember
that this is based on the lack of information that we have about
Americans of all sorts. Everybody has been considering lesbians
to be the group who is at lowest risk for infection with HIV.

Although all too scarce and flawed, and this is just a
little of the data I'd hoped to present today but there isn't
time -- research conducted during the past 40 years describing
American sex behavior nonetheless alerts us to our grave lack of
information in this vital and the fact that none of us or our
families or friends are really isolated from or completely safe
from this threat.

We all live in overlapping communities of risk. With
self-control and modification of sexual practices serving as the
only protection against sexual transmission of human
immunodeficiency virus (HIV), a precise understanding of sexual
behavior in the various ethnic, racial, social, age and sexual
orientation groups which constitute our society and an
appreciation of the methods, procedures and techniques necessary
to derive accurate data are essential in the identification of at
risk groups and in the design and implementation of educational
programs directed towards attitudes and behavior change.

What are my suggestions for guidelines for future
research?

First, we are a heterogeneous society and when it
comes to sex, this factor is even more meaningful. We must
accurately identify, acknowledge and target for research and
education our subcultures. For example, American Blacks are not
a homogeneous group. They minimally include Haitians, Caribbean
Blacks and Afro-Americans. Our American Hispanic group culture
includes Cubans, Puerto Ricans and Mexican- Americans. They are
not the same. For example, the Mexican culture in America is
based on the Mestizo culture of Mexico, a mixture of AmerIndian
and Spanish culture. In that culture, male anal intercourse is
only considered homosexual if you are the receptive partner. If
you are the insertive partner, you are considered heterosexual.

106

 

 
Heterosexually, anal intercourse is used to maintain vaginal
virginity before marriage and as a contraceptive method after
marriage.

This is only one tiny example. We cannot believe that
we understand any one group just because we have some information
on white, middle-class Americans, which is by the way also
inadequate.

Secondly, in any survey research we must over-
represent, we must over-sample ethnic, racial and subcultural
groups.

Thirdly, interview schedules and questionnaires must be
developed by as wide a variety of individuals representing as
many subgroups as possible.

Fourth, interviewing should be conducted by
interviewers matched to subjects on at least sex and race, if not
age.

Fifth, and perhaps most important, vernacular -- that
is, the language of the culture -- must be used instead of
sanitized, often incomprehensible language. That is, explicit
language and visual aids targeted to specific groups must be
permitted if meaningful sex behavior research and effective
behavior change programs are to be developed to halt this
dreadful epidemic.

I have interviewed women seven months pregnant, sitting
with me at the table, and I have asked them whether they have had
vaginal intercourse and they have answered me, "no." And when I
asked them, "Well, how did you get pregnant?" they have other
words in order to describe the activity that caused them to
become pregnant, but "vaginal intercourse" is not one of then.
They don't understand the word "vagina" nor do they understand
the word "intercourse" because they come from a different
cultures and we have many cultures in this country.

Finally, the limited data available demonstrate that
these behaviors are not rare, that they are universally
practices, many of them at substantial levels in the
heterosexual community. Although there is no doubt that
practicing abstinence assures complete safety from sexual
transmission of the virus, even some individuals who have
dedicated their lives to God are not successful in maintaining
sexual abstinence. As I am sure you are all aware, there are
more than 20 reported cases of AIDS in Catholic priests.

We must develop techniques for helping people to
practice all sexual behaviors with care and thoughtful self-
control. To do this, we must appropriate major public funding

107

 
 

 

for research describing American sexual behavior and developing
behavior change strategies that are succinctly targeted and
explicit about sex and drug use. To draw limits for or to deny
funding to groundbreaking research cripples us in our search for
the weapons with which to fight this devastating disease.

DR. CRENSHAW: Thank you very much, Dr. Reinisch. You
did a remarkable job of covering an enormous amount of territory
in a high speed, very condensed period. We will save questions
for all of the panel members until the end of the presentations.

Dr. Voeller?

DR. VOELLER: I am Bruce Voeller, I am President of the
Mariposa Education Research Foundation, and our main area of
research and education being in the field of human sexuality,
with particular emphasis based on my training as a physiologist
and biochemist in the area of physiology of human sexuality and
prevention related to that.

A group of us at the University of California Mariposa
Foundation and University of Southern California have the
principal Federal contract for the testing of the efficacy of
condoms and spermicides, both in laboratory work and in clinical
trials. We have already completed a comparable study for the
British Government in that field. That is something of my
background. I also am the one who gave AIDS its name.

Dr. Reinisch and I agree that at some levels, there was
not sufficient time under the circumstances for us each to lay
out an array of things to tantalize you with what might be more
interesting broadly if there were more hours to hear from us, so
she presented an array of information of the sort you just heard
and I repeat, to tantalize you, to wet your appetite for what is
really behind all of that and Dr. Gagnon will present additional
related materials.

I want to look back just a little bit and specify what
I think some of the problems are and what we need and why we need
it.

Kinsey and his colleagues published their original
volume in 1948, the first being on men and the second on women in
1953. In those two words, such a high standard of scholarship
was set, that they could not be lightly dismissed. Kinsey and
his colleagues thrilled researchers on the one hand by their
daring and by the accomplishment and quality of it on the other
hand shocked the public and its leaders.

Their careful, skilled interviewing revealed a vast
chasm between what Americans thought that they did sexually and
what they actually did. On the other hand, Kinsey and his

108

 

 
 

colleagues established truly the first substantial database on
the very sexual practices and the pure extent of sexual
expression, total sexual outlet.

On the other hand, Kinsey and his colleagues in doing
that, demonstrated how ill informed were those who advised the
public on sexuality and how oblivious they were to their
ignorance. It is as true today as it was half a century ago,
despite the much eventide sexual revolution, I might add.

Few know the persecution that Kinsey and his
colleagues, and I know no better word or more accurate word than
"persecution" to describe it, few know how much they experienced.
Denunciation by physicians and ministers and priests,
denunciation by politicians, by statisticians, even a major
congressional investigation was launched against Kinsey and the
Institute with all the public attendants related to that. As a
consequence, they lost all their funding. They had been
supported by the Rockefeller Foundation throughout the early days
of the project, until the publication of the volume on women, and
the notion that women could be sexual, as Dr. Reinisch has so
clearly demonstrated in her slides, and it was more than the
public or Congress could bear.

What lies behind all this? Someone neglected, because
of the enormous press surrounding the Kinsey publication, two
very distinguished Yale professors, Ford and Beach, published
another book, “Patterns of Sexual Behavior," in 1952, a couple
years after the male volume by Kinsey, a year before the female
volume. They did that at the same period but they were somewhat
eclipsed by the Kinsey celebrity, as far as the public was
concerned.

Ford and Beach compared sexuality in some 200 cultures
around the planet, and among a wide range of animals, looking at
in essence the evolutionary history of sexuality through species
including a wide range up through primates. One of their major
conclusions was that of all these nearly 200 cultures which they
reviewed, our culture, the Euro-American culture, was one of the
three most sex-phobic on the planet.

Why then would we expect to have a high premium on
scholarship in human sexuality? Dr. Reinisch outlined some of
the things we know and which bear on the issue of AIDS and
related social issues. The great point, however, is we have a
shocking lack of such information.

Those of us who do research are all too aware, those of
us in the area of human sexuality, that our colleagues look at us
with suspicion, even those of us who are doing basically
physiological research, never mind those who are in the more
behavioral aspects of it.

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At universities today, not much has changed from the
Kinsey days. We have entire schools of journalism at most of the
major universities in this country. We have whole schools, not
just departments, schools of home economists, athletics, on and
on. Cornell University even has a distinguished school of hotel
management. There is not one department of human sexuality or
research on sexuality in this entire country with the exception
of the Kinsey Institute linked with the University of Indiana,
although a private corporation, and the Masters and Johnson
Institute and a few others which are small, independent units.
We do not have major institutions at our universities to
investigate and to make social and public scientific commentary
upon the great issues that face Americans.

It is quite extraordinary that our sexuality enters
our awareness throughout the day repeatedly. Our social crises
in this country and throughout the world linked to sexuality with
unwed mothers unable to provide for and educate the next
generation of Americans; crises in sexually transmitted diseases,
the most recent of which is but AIDS, and in all likelihood is
but the forerunner of additional diseases which may be equally
devastating if not more so if we don't learn the lessons which we
better be learning, and I feel we are not.

To me, it is fascinating that so little study of one of
the most central aspects of our personal lives is so ignored,
that its implications on our social, political and moral lives
has been so unstudied in terms of evidence and data on human
sexuality and indeed, it obviously represents the very core of
our evolutionary past, present and future as a species on this
planet.

I would like to turn to "sexpertise" as a part of that,
I alluded to it. We know so little about sex actually that every
newspaper reporter, every rabbi and priest, every politician and
every physician, even though they have never been trained because
there are no courses or very few in medical schools and not a
requirement to take the ones that do exist, every one of these
people considers himself or herself an expert on human sexuality.
The main people to whom the public turn for their information,
their counseling and the like.

It is a rare person, indeed -- I've had the privilege,
having served on most of the Federal commissions on AIDS, with
FDA, CDC, NIH over the years, since 1982, one after the next, I
have had the privilege to work with a few people out of that
grand total of literally hundreds of researchers and physicians
who make up those commissions, who have really genuinely knuckled
under and begun to learn about human sexuality. June Osborne,
who several of us have become good friends with, because of her
keen awareness of the lack in her training, her willingness to g
out and. begin to learn. Roger Edles of the University of

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California, June Osborne is the Dean of the School of Public
Health, University of Michigan. Roger Diedlestein is the former
Dean of the School of Medicine at UCLA, School of Public Health.
Again, he have taken the time to learn that his training didn't
provide him that. Most of the other people I've met on these
commissions do not know these things.

For example, the heads of all the major organizations
dealing with blood were debating all the issues concerning making
safe the blood supply and we turned at one point, and having been
on that commission over the years which June Osborne chaired, we
turned to the issue of why it is that even though 90 percent of
hemophiliacs are infected with the AIDS virus, or at least with
HIV, they seemed at that point to develop clinical symptoms as
well as their spouses than did people who contracted the disease
in other ways.

A part of the problem in looking at whether there was
some underlying physiology that might be instructive and
interesting for everyone, it hinged on why was it that some
hemophiliacs seemed never the less to go on apace with the
development of clinical symptoms and the like. Until after
sitting for nearly two hours, I pointed out that some of those
hemophiliacs might well be homosexual and I could guarantee some
were, and indeed, some of them were probably addicts as well.

The head of one of the major institutions turned to me
and said that was an outrageous suggestion, was I suggesting
there were homosexual hemophiliacs, and I said, well, I happen to
know several.

You see why my central point, and I think you are
beginning to see the drift of my argument, why I feel that it is
so essential that we make people aware that they are trying to
paint the landscape of the course for the future of our handling
of the crisis, they are painting a technical portrait but they
are color blind. They lack a full palette when they don't know
about human sexuality.

I suggest that it is understandable in the context I've
tried to paint, of Ford and Beach's identification of us as such
a sex-phobic culture and with the evidence of it in terms of the
research that is tolerated in this country, never mind funded,
that we put ourselves into that position and it should be no
surprise that we find ourselves where we are.

That discomfort is acceptable and understandable, to
allow it to drop at that is not.

In the present AIDS crisis and what I am sure will be
subsequent similar crises, we must learn more about human
sexuality and put it to work. That is absolutely essential.

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In the levels of physiology, as you will see from the
statement here, Drs. Masters and Johnson, two months ago we
prepared a statement and sent it along to the Commission, a
joint statement. There is a three page summary statement that I
hope you have been provided. We outline what we think needs to
be done. The sum of it basically is that we think and feel
strongly that it is critically important at this point that the
nation make a commitment and that the interagency rivalries and
the like which undermine that going forward automatically be
dealt with appropriately but that a major national commitment be
made to collecting and gathering the information of all kinds to
human sexuality, in our culture and elsewhere, and this must
include surveys, as June Reinisch put it, of who is doing what
with whom and how often, and we need to know the physiology that
relates to that. We need to know what all the physiology aspects
are and we must have data banks on everything from T-cell
information which has been so critical in the particular crisis
we are addressing now, through such things as what are the
components of semen.

Within the AIDS crisis, for example, at this point, we
don't even know, and I say this from the standpoint of someone
doing research on condoms and spermicides so that we don't know
whether we are in the ball park or not in a certain sense, we
don't know at this point in time such fundamental cellular
physiology related to sexuality as to what the component in semen
is that is infectious, is it virus bound to the head of the
mobile or modal sperm, so it can swim throughout the female
reproductive system vaginally or anally in either men or women,
is it white blood cells that have been infected with the virus,
we don't know simple answers to things like that, yet we are
asked to identify whether or not different spermicides from
around the world will be effective in preventing the sexual
spread of the AIDS virus.

We need to have databases that collect all that range
of information, behavioral all the way through the most elaborate
array of physiological information. We need to have that data
ongoing, not an one time shot just to address the AIDS issue and
then go our ways, and the belief that is that and we have solved
the problen.

We need to have an ongoing research database of the
highest quality and with the highest priority placed upon it and
the funding related to that to know what is happening with our
people in all of the subcultures Dr. Reinisch alluded to,
throughout this country and in turn throughout the world.

We have great arrogance, not even knowing what is going
on in our own country and offering solutions and recommendations
in such detail that we often do to the rest of the world, which
is so sexually and culturally different from us.

112

 

 

 
 

 

The point basically is if we don't have a commitment at
this point to building such a database, utilizing it, in the
moral life, the social life, the political life and the health

' gare of this country, we can expect the AIDS crisis to grow and

become worse. We will have lost enormous time as indeed we have
lost by not having had that commitment to such a database all
along prior, and we will be in a terrible position when
additional threats come to us.

Thank you.

[The prepared statement of Dr. Voeller follows in the
Appendix.

DR. CRENSHAW: Thank you, Dr. Voeller.
Dr. Gagnon?

DR. GAGNON: My name is John Gagnon. I am a Professor
of Sociology at Princeton University this year. I'm normally a
Professor of Sociology and Psychology at the State University of
New York at Stoneybrook.

I probably have spent the largest portion of my
professional life doing sex research. I am this year the
President of the International Academy of Sex Research. I come
to you, third, which unfortunately extracts most of the things I
was going to say, the least of most of my laments about the
status of the field.

Let me just reiterate what was in my written comments
with two additions. I think Dr. Reinisch and Dr. Voeller both
pointed out the lack of data. That is we are absent for a period
of nearly 40 years only very fragmentary pieces of research that
have been done, and if you look across the entire spectrum of
research, what we see is this enormous lack of data.

We have no data which give us any baseline information
on where the epidemic may be taking us. We have great difficulty
understanding the likelihood of transmission, for instance, if we
don't have data on what people are doing sexually.

Let me make another point. The kind of data we need
for transmission may not be the kind of data which we need for
behavioral change. You may need data on partners, sexual
techniques and other kinds of things to map either analytically
or empirically what the epidemic is going to do.

In behavioral change, you have to understand a great

deal more about those lives and much more about the way their
sexuality fits into their general life.

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A second point, why we are all here is really about
AIDS and we are once again, as this culture tends to be,
interested in sex because it appears to be driven by a problem
which we have. We are interested in sex among adolescents
because we are worried about teenage pregnancy or the sexuality
of communities where there are large numbers of STDs and we are
interested in their sexuality.

It is quite different to be interested in people's
sexuality because you want to understand their sexuality, not
because you have a problem about it. One of our difficulties is
that we let the problems drive our research all the time, rather
than attempting in some sensible way to keep constant monitoring
or understanding of where sex fits into the lives of people who
currently are not in trouble. That does not predict they will
not be in the future.

The lack of the research tradition in sexuality really
has a number of consequences. Some of you can see the simple
consequences and the fact that we frequently don't even know how
to ask the questions appropriately to get reliable and valid
answers. More complex, I think we have a situation in which
sexual research is interdisciplinary research. We have very weak
traditions and collaboration between sociologists and biologists.

A second question is the research is not cumulative, we
don't add on to what we have done before. We have sporadic
outbreaks, so that Kinsey appears as sort of a media villain,
Masters and Johnson appear as sort of media heroes, so what we do
is we don't have a good sense of a long term cumulative tradition
which trains graduate students, which has some density of people
constantly working in the field, and it is really necessary to
have a tradition of work going on, so that young people can be
trained and replace people who are not doing work any more.

I think this has a deep impact on biomedical research.
Much of the research which we report right now about AIDS is a
combination of biomedical research combined with behavioral
research. The biomedical research frequently is very strong,
very robust. The behavioral research, asking people about their
lives, which goes on with that biomedical research, frequently is
very weak. That is because nearly everybody thinks they can do
sex research. Not only does everybody think they know everything
about it, as Dr. Voeller said, but everyone thinks they can
design a question, they can ask questions and get good answers,
and in fact, if you ask simply about behavioral change items, the
reliability and validity of those items, have you changed your
behavior in the last "x," we frequently do not have any sense of
the validity or reliability of those items.

114

 

 
 

 

I wanted to suggest a number of recommendations to you.
I think we need more sex research and I think we need a lot of
it. I think we need a number of things to go with it. We
desperately need research quality control. Dr. Reinisch has used
surveys done by women's magazines, men's magazines, and we all.,
know the defects of that research.

The American people want information about sexuality
and they are willing to read it in Redbook instead of reading it
from reliable people. The fact that we don't fund sex research
doesn't mean that people don't want to consume information about
themselves, and that people in society have a right to know about
the sexual life of their society. They have a right to know, we
tell them all about their voting behavior.

I think one of our crucial issues is really research
quality control. We really have to begin to establish ways of
upgrading the quality of work which is done in sexuality in
society. That can be done a number of ways. They are not very
expensive. Maintaining peer review, this work that really
involves kind of research coordination. I don't mean that
essentially we need an AIDS czar, no one should be deciding every
question everybody should ask.

At this moment, at least four or five major studies
concerned with AIDS surveys are now being planned with very
little interconnection between what is going to be asked, what
should be asked, how can it be asked, all of those require
investments in research methodology. I'm not sure I have a
number for this but I would think at least one or two percent of
all granting money in social and behavioral sciences should go to
methodological research. That is we should be spending money --
it is much worse to believe we know something and be ignorant
than to know that we are ignorant and frequently in this area, we
have spent all of our time being systematically - - you read the
numbers but you can't believe then.

I think if one looks very carefully, for instance, at
the document which was given to this Commission on what the
incidence of the virus is in the population, all of those numbers
have to be taken with an enormous grain of salt. They are not
sample populations. They are peculiarly gathered together.
Whatever numbers you get from that are numbers which you have to
play with very carefully.

Let me suggest two other things. One is training. The
epidemic is going to be with us for a while. We need to train
the people to replace the people who are currently doing the
work. Training grants are essential. They might be
interdisciplinary. They have to work between both medical
schools, colleges of arts and sciences, people have to know about

115

 

 
 

 

virology. I think such things can be done. We have done it in
the past. I think that is absolutely essential.

Finally, there is a question of data archiving and
sharing. One of the problems in science is what makes you famous
and gets your name on an article first, that is that is what
makes you a great scientist, but it also makes people hoard their
data. Data which is gathered with public funds ends up being --
they hold the data until they can publish. Indeed, the New
England Journal of Medicine will not publish data which in fact
you have handed out reprints of at a scientific meeting. It
encourages a situation in which both data and knowledge is
restricted and as part of that kind of strange relationship in
science, which is awards are given to individuals, but the work
is really done by collectivity, that the scientific advances is
never the work of one person, but awards, like the Nobel Prize,
are always given to one person.

Data archiving, data sharing, I will tell you about
what I see to be a real tragedy. The National Institute of Drug
Abuse had a large data archive of surveys which were on surveys
of drug abuse. They held that archive together in an university.
They stopped funding that archive some years ago. We now do not
know whether or not we can put that archive back together. That
would have been baseline data on large aspects of drug abuse in
society.

Finally, I think I want to say a couple of other
things. I think sex research is meritorious in itself. I think
it is perfectly good to be curious about sexuality and to tell
people about it. I think it is as good to be interested in that
than it is to be interested in the secrets of the gene or the
workings of the atom. That is that research about this can be
driven by your interest and understanding why people do it, not
because you have a virus in the world. Indeed, asking questions
from the point of view of only the virus will distort your
interest in sexuality. Sexuality itself becomes the problem.
The virus is the problem. Sexuality is not the problen.

I think that our failure to do such research in the
spirit of understanding and social enlightenment really is a
fundamental ambivalence about sex in society which Dr. Voeller
talked about.

Social research has a peculiar character. It is
consequential to the lives of people in society. The atom does
not care if you are wrong. The atom does not care if you
misconstrue what it is doing. If you are wrong in the social and
behavioral sciences, institutions and organizations gather
together to respond to what you are doing. If you think that IV
drug users are absolutely out of control and indeed are hardened
sinners, and you believe they will not adopt health care

116

 

 
practices, you then design programs to treat them which acts as
if they will not tender to those practices. If you think that
gay men are narcissistic and that is why they have sex with other
men, what you will do is you will act towards them and you will
create programs which in fact are based on that misconception of
who they are. That is the helping behaviors that have occurred
among gay communities providing social support belies every
single argument about narcissism among gay men.

I know people who have given much of their lives for
their friends. They have given up promotions at universities. I
know very few other people I can say that about.

I think we need to understand sexuality from the point
of view of the actor and we need to include those people who are
doing the sexual things as part of our understanding of them. We
don't want to dominate people's lives on the outside. That is
one of the careless aspects of science. Science is a powerful
instrument and we frequently overwhelm our subjects by telling
them why they are doing things. We need to hear their voices as
well. I think we need increased participation by the subjects in
research.

I don't have any immediate recommendations on how many
millions you would spend and I don't want to be that kind of a
immediate supplicant and leave a grant application on your desk.
I think we need to spend some money. I think we need to think
about it fairly quickly. I think we need to do those things in
the scientific community which will get research on line quickly
so we can get data back quickly. That may involve sort of
shaking up the scientific establishment about how it allocates
funds.

Thank you very much.

| [The prepared statement of Mr. Gagnon follows in the
Appendix. ]

DR. CRENSHAW: Thank you.

I would like to open the discussion for questions now.
I would like to lead off by asking you to comment on the
misperception of sex research and sex therapy as in a vacuum of
genital phenomena without connection to the emotions or the rest
of the human being. Perhaps we can put it a little better in
context before we begin with the additional questions.

DR. REINISCH: I believe you are asking about the
perception that sex research is not concerned with the emotional
and love values. I don't think that has ever been the case. It
is just that in any kind of scientific endeavor, one has to very
carefully define what one is going to look at. I think there is

117

 

 
 

 

no question that questions regarding emotions, attitudes and
values are a very important part of sex research.

Kinsey asked questions regarding that although people
said he didn't, he did, and there are both books, and so have
many other sex researchers who have had the opportunity to
interview people about this subject.

One has to keep in mind that sex behavior itself, a
very firm and careful description of it in our country today and
I hope continuing, is essential to many of our major problems. I
know people aren't mentioning this here but I would like to
mention it, the fact that AIDS is a very major problem. We have
other very major problems that relate directly to sexuality and
had we been studying them, we would be dealing with them better
today than we are.

Teen pregnancy is another one. We spent over $16
billion a year on families begun by teenage girls, every year.
We have been doing that for 10 to 15 years already in this
country. $16 billion. The problem is a sexual one. We don't
understand the sexuality of adolescents. We don't understand how
to deal with them and help them to be more responsible in the
context of their families, in the context of their communities,
religions and so forth.

At the heart of it lies their sexual behavior. We just
don't have the data to make these programs. I want to make it
really clear that what you are going to hear after us, from the
panel on behavioral change, it is really not possible to make
completely effective programs without knowing what people are
doing because you can't educate them. You can't train them
unless you know what they are doing.

DR. CRENSHAW: Without the baselines.

DR. REINISCH: Exactly. I think we have to ask people
simultaneously about their behavior as well as about their
attitudes, their emotions, their feelings, their responsibilities
with regard to sexuality. That can be done. There is no problem
with that.

DR. CRENSHAW: Thank you. Dr. Lee?

DR. LEE: My father told me when I was very little that
the most important thing in the whole world was sex and if I saw
avalanches, bankruptcies, wars, unhappiness, buildings falling
down, if I got to the bottom of it, it would be sex. Dad, you
were right!

[Laughter. ]

118

 

 
 

I am glad that we have you people here.

When we get to your area in AIDS, it seems that what we
are really focusing on is multiple sexual partners, and
promiscuity. That's the dangerous thing, sexually, for us all.
If we look at your interconnecting circles and if one is
promiscuous, that "funnel" opens up very dramatically,
particularly in certain communities. When we listened to Dr.
Davis talk, if really 20 to 40 percent of the women in a
community are HTLV-positive, and one is having sex with large
numbers of people, you have a bad set of problems.

What do we do about this? Do you have any ideas on how
we approach promiscuity? We certainly can't do much about
sexuality. It is here, like hunger and need for shelter. But,
what can we do about promiscuity? Is there a relationship
between some sort of societal or family breakdown, the subunits
of our society? Are we seeing social breakdown with increased
promiscuity? When you look at animal behavior under these
conditions, that happens.

DR. REINISCH: I don't think we have any evidence to
support the fact that there is increased numbers of partners at
this time in history. Again, one of the problems is we don't
have the research to support that. People have all kinds of
ideas, myths and beliefs about sexuality, including the one that
somehow our society is becoming more "promiscuous." I put it in
quotes because we don't have the definition.

The second Director of the Kinsey Institute used to
define it as one more partner than I've had.

{Laughter. }

DR. REINISCH: That is really not a joke, we just
really don't know the answers to what does that mean, what does
the average person do, in what country, in what community, under
what circumstances. Are you promiscuous if you have three
husbands and each one of them dies and so you fall in love and
marry another one. If you have had four partners in your life,
does that make you promiscuous or equivalent to being
promiscuous.

Again, I have to say we would love to be able to answer
your question, Dr. Lee, and what we need is the appropriate
research data, not just from one community, we have multiple
communities here. We can't do a national survey. It is
impossible. We have to survey the different cultures and
different groups of our society probably separately. We would
then be able to answer your question, and then we would have to
do it over time, so that we could tell you whether there has been
a change.

119

 
 

Everybody was very upset about Kinsey's data because he
showed in the 1930s and 1940s that 50 percent of women were not
virgins when they were married and that extramarital sex was
going on at a rather high rate in both males and females in the
1930s and 1940s.

We really need to have good research over time to be
able to answer your questions. I'm sure there is no doubt that
family upset and the problems that we are having with divorces
and so forth are important, but I can't tell you how they are
important. I would like to be able to do that because then we
could move in with programs to mediate what is being lost or
hurt.

DR. LEE: We know how they are important. They are
important because we see terrific social damage and we are now
seeing AIDS, you are increasingly at risk if you have multiple
sex partners.

DR. REINISCH: And you are not responsible. The
limited data we have seems to show that if you are responsible
about your sexuality, then the number of partner is not that
important.

DR. LEE: Is that right?

DR. REINISCH: Yes, responsible sexuality is the thing
we are talking about. As you said, we can't stop sex on this
planet. It has been tried by many groups around the globe, or to
limit it or make certain things illegal. There are times in our
own history when certain behaviors would be punished by death.

It didn't stop people from doing then.

We need to talk about responsibility.
DR. LEE: I can understand that.

DR. REINISCH: And so does your dad. We need to
really be talking about responsibility and how we are going to
train people, to educate them, to understand how to be
responsible in their lives. If that means abstinence, that's
great. If it means monogamy, that's great. If it means using
condoms and spermicides in the appropriate ways, that also will
help us stop this epidemic.

DR. LEE: In the inner city, underclass communities,
where we are seeing single parent households, teenage
pregnancies, illegitimate children at a very high rate, where we
are finding the highest percentage of HTLV positivity, the
highest percentage of drug abuse and what appears to be a
breakdown in the system, that is what I was referring to.

120

 

 
 

DR. REINISCH: Teenage pregnancies and sexual abuse of
children is not limited to the underclass; that's one thing we
really do know and research has told us. Sexual abuse of
children and incest and teen pregnancy is found in large amounts
throughout our society at every level.

DR. GAGNON: I think we have to sort of segregate out
the kinds of problems, I think we have to distinguish between
child abuse and STDs and that kind of thing. I think there is
one crucial issue here. It seems to me that what you point out
is perfectly true, but what we may be seeing here is simply in
addition, a disease burden of the poor. That is HIV may be added
to the sexually transmitted disease process, to teenage
pregnancy, even though it is widely distributed, it does exist
there.

It seems to me that what is happening is we are losing
a portion of society because we do not extend medical care to
them. I would argue there is considerably more movement out of
the underclass than most people think, it is not an iron wall
between poor people and the rest of us, but I think the real
point is there is a kind of failure to respond to the poor in
society and that a whole series of structural issues other than
sort of responding to the HIV issue, and they really have to be
taken into account here.

I think drug addiction and teenage pregnancy all have
to do with the kind of failure to face what the poorest portion
of this society are living like. I think it links to HIV but if
you asked me how to change it, I wouldn't be talking about simple
disease control.

DR. VOELLER: I would like to comment a little on that
too, and that is we have to go back a bit and look too -- for
example, using gay men or using racial minorities in this
country. But take gay men as an instance: If you deny gay men
all of the buttressing strengths that society provides for
heterosexual relationships, that is to say everything from double
fares and insurance rates -- well, fare rates on airplanes and
insurance rates for cars, all the way through religious
documentation and validation of relationships all the way through
what families think about those who are same sex couples versus
cross sex or two gender couplings -- if you don't provide the
routes of support, economically, socially, psychologically and
the like, then you shouldn't be too surprised if you have gay
males acting at a certain period in time with a different
behavioral outlet or expression than what the general society
thinks is appropriate.

I would suggest however equally if you have a look at
the behavior of male populations which are heterosexual -- and
our armed forces are a great case in point -- in the First World

121

 

 
 

 

War all the textbooks of syphilology point out that one of the
major studies of American troops in France showed that 60 out of
every 100 men every month were absent from duty because of
syphilis or gonorrhea, which they didn't get by toilet seats.

The point is that when you have no support for relationship of
diverse sorts I've said and you have male societies, whether they
are heterosexual or homosexual, you get a high sexual outlet. If
you want to address some of those problems, you are going to have
to look at changing those factors -- which is going back deeply
-- just as are those issues related to solving our problems with
poverty and the related social and political problems that, in
turn, creates. You can't ignore those. They are not easily
solved and they won't be solved during the course of this crisis.
But it is an opportunity for the commission to address some of
those issues and lend its support to the forces which would see
those remedied.

DR. LEE: We are not going to ignore those issues.
DR. CRENSHAW: Dr. SerVaas?

DR. SERVAAS: My question is for Dr. Reinisch. I'd to
like to know what the Kinsey Institute or you know about the
number of teenagers who are sexually active and you are having
intercourse and at what age. How many ten-year-olds, eleven-
year-olds, twelve-year-olds? Could you give us the really bad
news about that? The Children's Better Health Institute wants to
know.

DR. REINISCH: Dr. SerVaas, we do have those data at
the Institute, which we could provide you. I'm sorry I didn't
get the question in advance.

But let me just say that children are -- there are
several places in this country where there are pre-teen
pregnancy clinics, and I have talked to youngsters who are on
their second pregnancy before they become a teenager, so that we
know that this is certainly happening very early. By I believe
about age 16 the average American adolescent has become sexually
active in terms of having his first intercourse.

It is very important to understand that in the few
studies that are available, many of them done at the National
Institute of Child Health and Human Development, it appears that
education not only lowers the pregnancy rate -- and in fact the
repeat pregnancy rate -- in one study from 60 percent for second
pregnancies to 2 percent, but it also appears to delay first
intercourse significantly. So, unfortunately there are many
people in this country who believe that sex education is actually
going to make children more sexually active and is going to make
them more involved sexually and in fact the data that are
available, and we should have a lot more -- I agree with you,

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show us the exact opposite -- that with the proper education,
with the proper availability of contraceptive materials, with
education in a context of values, morals, the religious community
of that community [sic] that children will make the right
decision but they can't do it from ignorance. I can't think of a
time in the whole history of human development that ignorance was
better than knowledge.

DR. SERVAAS: I had one other question to you, and that
is, in the Orient, do you how many homosexuals there are
percentage-wise in the Orient?

DR. REINISCH: Well, it appears from the little work
again that has been done around the world, that the percentage --
and again the question is "how does one define homosexual?" -- is
that any man who has had one interaction sexually with another
man? Well, Kinsey and other studies have shown in this country
that it is about 37 percent of all men.

Are we talking about men who choose only to be with
other men, exclusive? That is a small percentage. That is more
like 4 or 5 percent, as far as we could tell. Our guess would
be, and again we could use data from around the world -- is that
the percentage would probably hold pretty constantly in most
societies, even when -- and there are societies that have been
discussed by anthropologists particularly in New Guinea in which
young boys are -- the ingestion of semen directly from another
male is part of their masculine development and every male does
that for six to eight years during their childhood in order to
become fertile. That is what the belief of the society is. And
yet the percentage of homosexuals is no different than that in
our culture once they are allowed to marry and have families.

So it appears that the percentage, from the little we
know and again we would like to know a lot more -- is probably
relatively, of those who are exclusively homosexual or wish to
be, and some people don't act -- is relatively consistent
throughout the world, but again that comes from very limited
data.

DR. SERVAAS: Thank you.
DR. CRENSHAW: Mr. Creedon?

MR. CREEDON: I wonder how or what kinds of surveys
would we have to do to get an accurate picture of the sexual
activity of people in the United States -- I mean there is about
250 million people, whatever. The activity is probably different
in San Francisco and New York than it is --

DR. REINISCH: Absolutely, that's right. It is not
just social group, it is not sexual orientation group, it is not

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just ethnic group. In fact, two things that groups tend to
differ on the most are food and sex. There is where you find in
fact an enormous amount of difference.

Yet ~- also geographically --

MR. CREEDON: That is what I'm saying. How extensive
would the surveys have to be? And secondly, the followup
question is, how reliable would they be? In other words, people
have feelings of privacy about their sexual activities and how
honest are the answers that are given? I can see some people
taking them kind of as a joke or say, well, they are going to
confound the experts or whatever. But how reliable would the
data be and how extensive would the surveys have to be to get
reliable data?

DR. GAGNON: Part of the question is very technical.
That is, if you have small phenomena -- that is if you have
phenomena which occur at the rate of 2 and 3 percent in the
population, then your sample sizes have to go up substantially in
order to get accurate estimates if there is a population
estimate. If you have a population rate at which you may have
one or two percent --

MR. CREEDON: I am willing to concede that everybody
does it -- over a certain age.

DR. GAGNON: No, no. You don't want to concede that.
First of all if you look at some of the data there is a fairly
large proportion of the American population which is not terribly
sexually active and may in fact be active only with their
spouses. I think it tends to -- the problem is the question
really asked is precision and size. I would think that probably
if you wanted to do a national sample of sexuality in society in
which you got decent estimates -- there are two different
questions here -- decent estimates of rates of behavior, assuming
that people responded correctly, the sample sizes would be about
15-18,000 people.

And you would then need, if you wanted to look at the
stability of that behavior, because that is really what is
crucial -- how often do people change their sexual networks, how
often do they change their partner (add them or drop them), you
probably need to re-interview those people some time later.

DR. VOELLER: That is what I meant about ongoing --

MR. CREEDON: The second question is, the assumption--

DR. GAGNON: The second question is, can you get people
to answer. It looks like we have done fairly well on a large

number of fairly hard to do studies. The National Opinion

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Research Center and other people have in fact done research
about highly sensitive issues and have gotten decent answers in
those studies.

Now I think the problem with the question you raised,
which is the problem of response rates and will people tell you
the truth -- the reason I can't give you a hard answer on that is
that no one has ever let me do the research to find out.

You can do studies which are designed methodologically
carefully in which you can get decent estimates on response
problems. Such surveys are within the ken and within the skills
of the social science community. It is only our unwillingness to
do them and pay for them which in fact leaves us ignorant about
it.

I think we know a lot more than we think we know and we
know how to do certain kind of things actually quite well and I
think we could solve those problens.

DR. VOELLER: Just to carry on with that, I agree and I
think though that many people including in research, especially
those who have not been trained in interviewing techniques and
who now are doing extensive interviewing of gay men, of
heterosexual populations in the AIDS crisis do not know how to
conduct a proper interview and have no idea of the limitations of
what people are willing to talk about.

I have long felt that the onus of the word "homosexual"
is not really on "homo," which is what a lot of us have come to
believe, but rather on being identified and labeled "sexual" in
our culture. In fact, the presumption -- and I have heard this
again and again from those doing studies on the sexual histories
and the factors amongst gay men -- that lead to becoming infected
in the first place and, if infected, going on to develop various
clinical symptoms -- you know, the whole notion of co-factors and
the like. The point is that many researchers believe that if you
get a gay man to begin talking, he has already identified himself
as "homosexual," he will then open up and tell you anything you
want.

The fact of the matter is there are all kinds of
sexual practices that are done by gay men and heterosexual
couples which are even within gay circles are considered to be
shocking by some significant portion of the population. This led
to Centers for Disease Control, for example, to put an utterly
undo emphasis upon "fisting" as a cause and source of the spread
of AIDS early on in the epidemic.

We have seen that again and again and again. Take that
example a step beyond: if you were to go to any of the so-called
"leather" or "S/M" bars here in the city of New York, even

125

 

 
 

 

tonight, certainly over the past years when the crisis was
developing you would discover that many of them, as they
approached those leather bars over in the west dock areas and the
20s for the most part now, that many of those men would pull out
a red handkerchief and put it in their left rear pocket of their
blue jeans or whatever. The left means that they are an
insertive partner in the act. Put in the right pocket, it would
mean they were the receptive partner in the act.

Now in the first place, within the gay community the
act of fisting is rather shocking to a fair proportion of the
population to begin with, so the men don't put the handkerchief
in, many of them, until they get near or at the door of the bar.
Neither do they want to go into the bar and seem like they are
shy about it, so they quickly at the door or in the block
preceding it, put it in their pocket, in the wrong pocket,
ofttimes, suggesting that they are only insertive partners --
which as June Reinisch said concerning Black, Hispanic and some
White populations -- if you are the insertive partner, that is
considered macho and heterosexual. Whereas if you are the
receptive partner, even within the gay community, there is a
carryover of that aura.

So that when researchers begin -- the interviewing
techniques are exceedingly critical to getting the information
that you want to have. Heterosexual anal intercourse, which may
be a significant future route and already beginning route for the
spread of the disease here as witness the work done at Einstein,
for example , heterosexual anal intercourse is something that
most people are unwilling to talk about.

In the one survey that has been done on this, it has
been published by Dr. Bowling in San Antonio with a very large
population of women and updated currently to some 2,000
interviewed women, he finds that only by the third interview do
most of the women who acknowledge heterosexual anal intercourse
as a frequent practice in their lives, acknowledge it. It takes
three interviews. And having met him I could assure you he is a
very easy person to talk with and confide in compared to some
physicians.

He also surveyed his colleagues in obstetrics and
gynecology and found that almost none of them was willing to ask
such a question of their ob-gyn patients. So you see, in many
levels at which the problem is impossible.

MR. CREEDON: -- would be very difficult to get --

DR. REINISCH: Well, Mr. Creedon, I think that it can
be done and I think it is going to cost money to do it properly.
That is, it cannot be done over the telephone, it can't be done
with sending out questionnaires to people. It has to be done

126

 
 

 

face-to-face in face-to-face interviews by experienced -- not
just experienced interviewers, but interviewers who have
experience dealing with sexuality. People cannot be trained in
two or three weeks to be comfortable and good at asking sexual
questions. We are going to have to use our population I believe
of sex therapists and sex researchers and graduate students
working with sex researchers and sex therapists to be our
interviewers across the country. They: will then get some
additional training. But I think that you can't just take
somebody who is an expert in asking people about their taxes and
about what kinds of soup cans they have on their shelves and then
train them in two weeks or even four weeks to question people
about this very sensitive behavior.

I would also like to undo -- and by the way I think
that the interviewers have to be matched, as I said, for sex, for
ethnicity if possible, for racial group and probably for age in
order to get the best answers. Within a face-to-face interview
there are ways of checking to see if somebody has given you
misinformation. That was done in the Kinsey Institutes
interviews and has been since then.

But the most important point I guess I would like to
make as we get close to the end here is that we cannot be
stopped, sex researchers and the people who are coming next or
the people for behavior change programs -- for using explicit
language, vernacular, the language of the people to whom you are
speaking and for whom you are trying to educate in the education
and research and questioning.

Up to this point the government has been very strong
in interfering with the use of the language of the people in
research and in behavior change programs. Until we can speak to
people in the language they understand, in the words that they
understand and use every day, we will not be able to find out
what it is they are doing and what it is they want to do in the
future and what their attitudes and values are. So I make a very
strong plea here that the commission influence the powers that be
in our government to allow researchers to use the language that
is necessary to answer these questions and to train our people.

DR. CRENSHAW: Dr. Walsh?

DR. WALSH: One of the things that we have learned
during these months is to have a sort of pessimistic outlook for
the answer to the current problem in the near future. We are
constantly told education is the secret weapon, education will
lead to behavioral modification. You all have added to my
pessimism now because you have indicated really that we don't
have much of a foundation or base of knowledge to go on.

127

 

 

 

 
 

Now to help us, what would you do or suggest? I
personally believe the educational programs for behavioral
modification -- overall I am talking about -- that are being
sponsored are a total failure. Certainly, except in -- you know,
where you networking with the gay community in San Francisco and
so on where it has been successful -- the problem seems to be
that there are great differences of opinion on where you begin
and what you tell them, what you have got to work on, what you
have got to work with.

We see the incidence of sexually-transmitted disease on
the increase. We see the problem in the minorities, which is
making this into a real social crisis, as I think Dr. Gagnon
re-emphasized, among Blacks and Hispanics.

What can we suggest for the near future on what you do
know that we could do that would result perhaps in the
improvement of the educational programs that are being put forth
by our government? How can we persuade the churches, the Black
churches and the Hispanic churches in particular, to become more
involved? And what kind of material can we give them, based on
what you know? That would help us. I realize you can't answer
all that in the time allotted, but that is the kind of
information we really need, because you yourself say if you are
going to do the right kind of survey, it is not only going to
have to be a large one, it is going to take a long time to do it
correctly --

DR. REINISCH: Not with enough money. It probably
could be done in a year if enough money is provided.

DR. WALSH: But I think we just have to have something
because huge amounts of money are already being wasted on
educational pamphlets that are used to --

DR. CRENSHAW: Dr. Reinisch, may I ask a favor of the
panel? We are out of time, but this is one of the most important
questions we could address, and if what you could do is give the
very briefest of answers and then elaborate on it for us in
writing so we can introduce it into the record and give it some
careful attention.

DR. WALSH: Because we need it desperately.

DR. REINISCH: Thank you, Dr. Crenshaw, and thank you
for the question, Dr. Walsh.

I think what I just said before -- one of the reasons
that many of these programs are not working is because
permission has not been given across the board to use the
language and the explicit means that are necessary to educate
people. You can't talk about sexual acts without some kind of

128

 

 

 
 

 

visual help, so that people know what you are talking about. You
need to also use, as I said, the language that will communicate
to them, and neither of things has been permitted in most areas,
so many times you are speaking to people, as I just mentioned
before -- "vaginal intercourse" is not a word that everybody in
our society understands. The word "penis" is not used in many
parts of our society. So even the best planned brochures and
education programs without the proper language -- it is like
speaking a foreign language even though those people speak
English.

One thing that would help, that could be done
immediately, is a strong voice from this very important
commission telling the government that they must permit the use
of the language of the people in these training and research
programs. That would make a big difference and maybe some of
those programs that are not working would begin to work just with
that kind of change.

DR. GAGNON: Can I speak to that? I think that one of
the things you also have to add here is that we can discuss
whether programs work or don't work, but one of the reasons why
there is debate over whether they work is that no one designs an
evaluation procedure such that you would know whether they work
at the end. When you give money for programs, you must assign
money to evaluation so that we don't continue to build a series
of square wheels.

What we systematically do is we do a program -- you see
this in medicine -- we don't do a careful design. You don't know
whether the effect is a placebo effect or there is no effect, or
what effect you want -- and it seems to me that you have got to
build the methodology in so that you don't repeat the errors you
have already made.

DR. VOELLER: I'11 be real quick. The one thing I
would ask would be, because of the important of the question you
pose and import of sex researchers can have to say in addition to
those who are specifically going to follow us on this program, I
really wish there would be a way -~- if you have to invent it --
to have some serious time devoted to a longer consideration of
the issues of sex research at the physiological, the survey, and
behavioral -- all levels we have only touched on.

DR. CRENSHAW: Than

DR. LILLY: I am going to ask Dr. Voeller a question
which under any decent of circumstances would elicit a two-hour
lecture. I am wondering if you could say briefly and succinctly
what your research into condoms has consisted of and perhaps what
kinds of things you are finding.

 

129

 
 

 

DR. VOELLER: Well, first, let me just say that there
are two separate studies at the laboratory level. We are doing
the major study that is funded by the government, and the
Consumers Union, who we have been collaborating closely with, are
doing a separate study of the strengths, weaknesses, the flaw
levels and rates and so forth of condons.

We are looking at roughly some 35 different brands, but
only testing a very large lot -- doing all of the international
and American standards, in contrast with the FDA, which only does
one of all those tests in screening all the lots that are
manufactured or distributed in this country.

We are also looking at HIV leekage through those
condoms and we find great variation. We find, for example, the
different brands of condoms, if you total up the score -- I
should say the lot we have looked at -- a large lot where we
tested a thousand individual condoms in a particular lot of a
particular brand. But the scores, when you tally up all values
in a weighted formula, can range from zero to 100, and we have
condoms that go all the way from 22 to 98 and a half. And they
vary in their HIV leakage. I would also add that we believe that
a lot of the data that has been put out, the pilot anecdotal
studies, frankly, on laboratory testing of condoms, are deeply
flawed -- giving both false negative (that's reassuring data) and
false positives.

The clinical trials will be begun once we have
completed the condom testing. We are doing similar studies with
all of the major STD agents including HIV, by which I mean
syphilis, gonorrhea, herpes, the lot -- we are looking at all of
those and seeing what the most effective spermicides out of
roughly a dozen different kinds from around the world, which ones
are the most effective.

DR. CRENSHAW: Thank you so much. I would like to end
this panel just with the comment that ordinarily under ideal
circumstances, before we can educate the public in a responsible
way, we need to educate the professionals and the experts -- and
we haven't had a chance to touch on this today, but educating the
educators is one of the gravest challenges that I see in our
efforts to get responsible information to the community at large.
It seems that we are going to have to somehow figure out how to
do it all at the same time. But thank you very much. We will be
in continuing contact and you will receive written questions to
help us further.

Risk Behaviors: Research and Interventions

DR. CRENSHAW: I'd like to welcome our next panel and
look very much forward to the comments. I want to preface it by
saying that in a world where information about sexual baselines

130

 

 
 

 

and so importantly, changing sexual behavior has become an

urgent priority. We need answers today that we were perhaps not
aware enough, thoughtful enough or active enough to fund research
on yesterday.

In that context, I know we are asking a great deal of
you, you have learned and you have a lot to present to us that
has been under funding conditions and opportunities to do the
very studies that we are asking for definitive answers about
today, but let's see what we can find out and what we can do to
close that gap.

Dr. Patrick Carnes?

DR. CARNES: My name is Pat Carnes. I am Program
Consultant to the Sexual Dependency Unit at Golden Valley Health
Center, which is a 450 bed mental health and addiction complex
just outside Minneapolis, Minnesota, and one of my roles there is
also to serve as the Clinical Director of their Institute for
Behavioral Medicine.

I was struck today as I was listening to the Commission
listen to the various testimonies about sort of the constant
themes, issues around research, around terminology, about lack of
information and yet having an extreme urgency to all the
questions. I found myself as I listened wanting to do
parenthetical comments and to leap in, as I noticed there were a
number of other people wanted to do.

I was even struck as June Reinisch was talking about
the problem of terminology, remembering in our sexual addiction
unit, one of the hospitals we worked with where we changed the
word "indecent liberties" because we couldn't get patients to
respond to the words “indecent liberties." We changed it to
"grab a feel," and we had lots of people who said they did that
but would not respond to "indecent liberties." We changed the
hospital admit form to have "grab a feel" on it which worked fine
until the Joint Commission of Accrediting Hospitals came by and
asked how we got grabbing a feel onto the hospital admit form.

(Laughter. }

It represents a lot of issues and I think one of the
things I would like to present to you is I think much of what you
are dealing with and the themes you are trying to address has to
do with the lenses that you use. The lenses I want to talk to
you about today is one that will give you a different perspective
but also an alarming one.

One of the things I want to talk to you about is the
role of addiction and sexuality, and not just what most people
associate in terms of addiction, thinking of chemical or alcohol

' 131

 

 

 
 

 

abuse, but I want to talk to you about other forms of addiction,
specifically sexual addiction.

If I could have my first slide, please.
(SLIDE. ]

DR. CARNES: What I have done on the slide is you have
a normal curve and one of the things is that it helps give a
sense of what we are talking about in terms of sexual addiction
or sexual "prowesslessness." If you think of sexual behavior as
a normal curve, one of the real accomplishments in the field of
sexology over the last 35 years has been able to give people
permission, whether they have had less experience or more sexual
experience, to understand that there is a great amount of
diversity in sexual experience and also a range in terms of how
much sexual experience people have.

On the far left, there is an area in which we have made
a great deal of success in terms of working in sexual
dysfunction, where somebody's inability to function sexually has
affected their life. We are talking about pre-orgasmic
conditions, inhibited sexual desire, or impotence, for example.

That we have talked a lot about and there is still a
lot of work to do but we have made a great deal of progress.

On the far right is a group of people who we have until
Jim Orford's article in 1978, received very little attention in
the professional literature. It is a group of people who
literally get to a point in their sexuality where it is not
having more sexual experience, it is an area where people lose
the ability to set boundaries around their sexual behavior. This
inability to stop their behavior, even though they can see
significant consequences and even risk their lives and not be
able to stop their behavior, is destructive to their life and is
an obsessional illness that we have come to understand under
terms like hyper sexuality, sexual addiction or sexual
compulsivity.

(SLIDE. ]

DR. CARNES: One of the things that helps when you
think of that curve, one way you can think about sexual behavior
and thinking of it as an addiction is to compare it to eating
disorders. Unfortunately, what happens with sexual addiction is
people immediately compare it to things like chemical dependency,
where they think of an abstinence model. The fact of the matter
is it is more like an eating disorder and if you think of the
normal curve in terms of eating disorders, you have some people
who eat more and some people who eat less. You have a group of
people on the far left who literally, their inability to eat

132

 

 

 

 
 

 

leads to self starvation which we call anorexia, and on the far
right, is a group of people who compulsively overeat. There are
34 million obese people in our culture, 14 million morbidly
obese.

When a person goes to treatment for an eating disorder,
they don't give up eating, they learn how to eat differently and
to monitor their rituals and learn about what healthy food is for
themselves. The same thing is true for sexual addiction.

People who are admitted to hospitals, in-patient or
out-patient units for sexual addiction, usually have not had
sexual experience as most of us would experience it, because of
the nature of their obsessional illness. The fact of the matter
is that many of them, starting when they were very small, entered
into a world where the actual experience of sexuality was not
something that they incorporated. It was more what happened in
terms of their obsession. ,

One of the things that has happened in the field is
we have started to notice that along with sexual addiction, other
addictions start to be associated, for example, compulsive over
eating women tend to be hyper sexual whereas compulsive
non-sexual or anorexic women tend to be compulsively non-sexual.

It would not be unusual, for example, to see a family
in which a husband is an alcoholic. He has been sexual with two
of his daughters for eight years, has a pornography collection
that is extremely large and has been having compulsive affairs
for years. His wife is 325 pounds. He is physically abusive of
his wife. His wife is physically abusive with the kids. One of
the kids is psychotic and another is learning disabled.

It would not be an unusual thing to see within that
marital dyad as he gets further out of control in terms of his
sexuality, his wife would be more and more compulsively non-
sexual. In other words, try to almost balance the marital
equation.

What we are understanding in the field of addictions is
many compulsive disorders co-exist.

(SLIDE. ]

DR. CARNES: For example, in a national survey we just
completed, of people who are recovering from sexual dependency,
we found that 42 percent of them were also alcohol and drug
dependent; 38 percent had some form of eating disorder; 27
percent reported compulsive work; 26 percent reported compulsive
spending and 5 percent reported compulsive gambling.

133

 

 
 

 

One of the things that is happening in the field of
addiction is we are starting to understand how out of control
behavior then impacts in terms of working with one another, why
is it, for example, a person who achieves alcohol sobriety will
suddenly find that their sexual behavior will start to get out of
control or even escalate far beyond the baseline that it had
before the sobriety was achieved.

A number of models are used to try to make sense of the
relationship among addictions. I have one example, a model that
takes the addictions and divides them into three categories, the
arousal addictions, which would be like gambling, sex,
stimulants, drugs and high risk behaviors. The satiation
addictions like over eating, depressant drugs and alcohol, and
the fantasy additions like drugs, marijuana and a whole category
of mystical and artistic preoccupations, that also goes in the
same type of obsessional illness.

What the authors do then is they do an analysis of nine
hormones that govern the electro-chemical interactions in the
synapses of the brain in terms of looking what we call in the
field cross tolerance effects. For example, at Golden Valley, 38
percent of our admissions are eating disordered. We know that
when they achieve some sexual recovery from their illness, that
50 percent of them are going to find their urges to binge eat are
going to increase and 50 percent are going to find that their
urges to binge eat are going to decrease. We don't know how that
process works yet.

I simply put it up there to show you that we in the
field of addiction are starting to understand that no addiction
is isolated, that they are intimately connected with one another.

One of the things that is real significant also in the
research is that we know sex addicts, in the national survey we
just completed, sex addicts have at least one addict, either
sibling or parent of another variety, 87 percent of those have
another addict in the immediate family.

(SLIDE. ]

DR. CARNES: To summarize what some of the symptoms of
sexual dependency are is to take a look at where a pathological
relationship exists with sexual behavior, which makes mood
alteration a higher priority than family, work, friends and
values. A sex addict has developed or cultivated the ability to
metabolize and to achieve a sexual high on specifically highly
focused fantasies and rituals to the extent that they would
sacrifice in order to preserve that behavior, their family, their
work, their friends and their values.

134

 

 
 

 

Another characteristic very important to the
recommendations I am going to make is these are literally people
who lose contact with reality through denial and delusion. We
have patients who have whole periods of their lives that they
can't remember. The fact of the matter is, as one of their
characteristics, they lose control despite obvious serious life
consequences and even risk to life. In other words, they will
see there is going to be disaster to their marriage, to their
family or their work or even to their life, and they will not
stop their behavior, which is very important in terms of thinking
about the AIDS epidemic.

[SLIDE. ]

DR. CARNES: Some of the questions that are frequently
asked about the origins of sexual dependency, there are many
aifferent things, and this is another category that the
Commission has to deal with, the fact that we could talk for
many, many hours about how sexual addiction starts. One of the
things is that we are getting very good at being able to pinpoint
when it starts. We know that most people who are sex addicts
have experienced a fair amount of abuse in growing up, about 81
percent of them have been sexually abused, 72 percent physically
abused and 97 percent have experienced some form of severe
emotional abuse.

In terms of the sexually abused, what we have learned
of sexually abused victims, that the men have pretty much -- most
of their sexual abuse has occurred between the ages of 5 and 8
and their out of control sexual patterns are already
identifiable by that age. Women have an onset somewhat later,
between 10 and 13/14. The reason that sexual abuse plays such a
high role in sexual dependency is the fact that what happens when
your care givers are sexual with you when you are young, you
misidentify that all care and nurturing has to be sexual. Part
of what happens for sexually dependent people as they mature,
they look to sex as a way to navigate their life.

In fact, one of the assessment tools we use is when a
patient starts to use medical language to describe their
sexuality, like my tension reliever, my pain reliever.

(SLIDE. ]

DR. CARNES: This is from a survey of sex addicts
anonymous. There are many different types of recovery programs
around the country. This particular survey was done in 1982.
The behaviors that were identified as key to the kinds of
behaviors involved and part of their addiction range from
masturbation, heterosexual behavior, homosexual behavior,
bestiality, right up through sex offenses, such as incest, child
molesting and rape.

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¢

What is significant about this is each of these
behaviors reached an extreme, for example, in masturbation, 45
percent of the men and 33 percent of the women had masturbated to
the point of injury.

What is important for our purposes, I took two pieces
out of a survey we have just completed that I think the
Commission can see that will kind of dramatize for you why I -
think it is important to look at the connection between sexual
dependency and AIDS.

(SLIDE. ]

DR. CARNES: If you look at the differences here, men
and women, for example, paying for sex, you will notice that men
are more likely to patronize saunas, massage parlors, with 30
percent of the sample saying that was part of a frequent
occurrence, as part of their addiction. Paying for sexual
activity, 47 percent, which is considerably higher than the
figures June Reinisch gave you as typical of our culture,
participation in phone activity, et cetera. In terms of
receiving money in exchange for sex or receiving drugs in
exchange for sexual activity, 24 percent of the women and 24
percent of the men.

A different thing happens if you take a look at
relationships in sex, if you just take having many relationships
at the same time, 40 percent of the men in the survey, 79 percent
of the women, having successive relationships one right after
another, 37 percent of the men but 74 percent of the women,
having one night stands, 62 percent, 86 percent, all of these
ratings are part of where people have talked about an extreme
level of functioning, behavior having a great deal of power over
their lives.

Engaging in sex with anonymous partners, 55 percent of
the men, 48 percent of the women. Swapping partners, 13 percent
of the men, 19 percent of the women.

Just one statistic about women. There was not one
woman in the survey who was faithful to her spouse within 90 days
of their marriage.

[SLIDE. ]

DR. CARNES: Physical consequences. This is one of a
whole battery of physical consequences that happen to these
people, ranging from continuation of sexual behaviors despite the
risk of disease or infection, 65 percent of men, 60 percent of
women; venereal diseases, 38 percent of the men, 45 percent of
the women, et cetera.

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The one that I want to bring to your attention is the
one that in the sample, sample of people who had been in
recovery programs, in other words, they had been through a
treatment program for recovery, and most of them, five to six
years. Even in this sample, we found 3 percent of our sample had
AIDS or AIDS related complex. The thing that I want to underline
for you and make clear is we are looking at a population who has
a very, very high risk because of the amount of behavior they
have and lack of discrimination and the denial they live with in
terms of their behavior.

We estimate that the size of this population is between
3 and 6 percent of the population was right under where eating
disorders and alcohol are.

I have four recommendations for the Commission.

-~One, in order to promote recovering individuals so
that they are less vulnerable to the threat of the disease or
AIDS, is to promote identification and diagnosis. The key
vehicles would be the National Institute of Mental Health, the
National Institute of Alcoholism and Alcohol Studies, National
Institute of Drug Abuse, to sponsor education about sex
addiction with professionals who treat related disorders,
including alcoholism, drug abuse, eating disorders and sexual
dysfunction.

--Two, we need to support researchers who are
documenting the role of sex addiction in the transmission of
AIDS. There are some very excellent research in progress right
now. People are struggling for financing, to figure out how to
ado that better.

--Three, we need to develop a study of the incidence
of AIDS in medical facilities currently treating sexual
addiction, both in-patient and out-patient facilities, so we can
see if the current people who are coming into the hospital, what
the rate of incidence of AIDS exists in those populations.

--Four, I think given the seriousness, it is like we
have two major illnesses that are sort of colliding. We have a
subset of our population who literally cannot control or make
judgments about their sexual behavior. They are one of the most
vulnerable risks in terms of spreading this illness, at a time
when we are really concerned about the epidemic nature of the
spread of AIDS.

One of the things that I think is very important is
that we put some effort into really studying this population and
promote successful recoveries. We do know that in this
particular survey, since we are looking for successful
recoveries, 77 percent of the 400 people in the sample said they

137

 

 

 
 

 

had been able to turn their lives around where they had five
years of no behavior that was dangerous to then.

That success is possible. We need to understand better
how they do it and how can we help people who have the same
problen.

Thank you.

(The prepared statement of Dr. Carnes follows in the
Appendix. ]

DR. CRENSHAW: Thank you. Dr. Friedman?

DR. FRIEDMAN: I am Sam Friedman with Narcotic and Drug
Research, Inc. of New York City, which is associated with the New
York State Division of Substance Abuse Services.

Given the probability that we are not going to have
either a vaccine or therapy for AIDS in the near future,
prevention of the spread of the virus is crucial if we are going
to get this epidemic under control. Given the fact that much of
heterosexual transmission is from IV drug users to other people,
then we have to get some kind of control on that, if we are going
to stop the spread of the disease, to groups that haven't been
heavily at risk previously.

We do not unfortunately have adequate knowledge about
how to mount these interventions. What I am doing here today is
chiefly to talk about research issues involved.

We need to learn how to affect risk and transmission
behavior. This behavior is deeply social behavior, not just
psycho-social but social. Transmission involves an interaction
between at least two people in which the virus can be exchanged.
The context that leads to contaminated syringes being shared, for
example, can involve small group pressures, it can also include
wide ranges of broader social factors such as those involved in
racial differences or particular laws in a jurisdictions that may
affect drug abuse.

These factors are hard to study, are complex. In
spite of chemical dependency, in spite often of no education
among IV users, in spite among many drug users of alienation from
social institutions, the common stereotype that says they haven't
done anything and can't do anything to protect themselves and
others in this epidemic seems to be wrong. We have abundant
evidence that people have tried to protect themselves and have
tried to protect others. Some of this has been presented to you
by my colleague, Dr. Des Jarlais, at a former meeting of this —
group.

138

 
 

Complexity is also indicated by comparisons between
gay men and their attempts to get this epidemic under control and
the activities of IV drug users. IV drug users have been much
less able to organize than have gay men.

On the other hand, in New York City, there is an
organization called ADAPT, of ex-users, some current users and
health professionals. In the Netherlands, there is what they
call the Junkiebonden, the drug users unions that have been
coming to terms with issues on AIDS. I have done some studies of
those.

The complexities of all these issues pose difficult
methodological and research problems, which I want to focus on
for a minute. Most research in this field has focused on what
helps the individual to reduce his or her personal risk of
becoming infected. It has been based heavily and at best on the
experimental model from psychology as a model, which means it
looks at individuals as the unit of change and that it assumes
that history is irrelevant. That is what works at one point in
time and at one place during the epidemic is going to work at
other times and places.

When I say this has been much of the best research, I'm
not saying that is the best research that should be done. We
need additional kinds of research to get beyond this.

We need to focus on reduction of behaviors that
potentially transmit HIV to others. This involves a different
set of motivations than personal protection. Many IV drug users,
for example, are more willing to listen to outreach workers when
the issue is raised in terms of protected their loved ones, than
when the issue is raised in terms of self protection.

We have to look at prevention efforts that take
seriously the fact that risk behaviors are social. We are
beginning projects to change the values of IV drug users and
their partners to reduce transmission and to help them to develop
ways to implement such protective ideas as groups, working with
groups of people in the street, for example, to develop ways in
which they can ritualize and set up norms by which they will
protect each other and support each other, for example, if
changes in their sex lives lead to break up of relationships.

We have to look at risk and transmission behaviors as
historical events. At the beginning of the epidemic, few drug
users believed in their own vulnerability to AIDS. Since then,
more acceptance has occurred and considerable reduction in risk
and transmission behaviors. Later on, we may well encounter a
subculture perhaps only part of the drug users, of despair, about
protection against AIDS. Each of these periods involves
different contacts for the individual and for the group who is

139

 

 
 

 

confronted with a given intervention, so we would expect
reactions to differ in accordance with the history of the
epidemic and the psychological experimental behavioral model of
research doesn't really deal adequately with this.

I might add in response to a question Dr. Lee raised
earlier that virtually no research is being funded that I know of
on how some of our more fundamental social structures may affect
risk behaviors.

Decisions about research are often taken by medically
trained persons and many of you here on the panel are medically
trained persons, often superb medical scientists are involved in
this. They make these decisions about what programs should be
set up, about which proposal should be funded, about which
article should be published and similar crucial decisions, on the
basis of what they know and on medical research training.

Their input is useful but social scientists have
developed understandings and techniques that go beyond what
people are taught in medical school and we have to develop ways
in which those understandings and techniques are brought into
these decisions.

The history of national research policy just prior to
AIDS becoming a major recognized threat is a warning to us, I
think. Good social science in AIDS is rare, as it has been
pointed out both by the National Academy of Sciences and the
American Foundation for AIDS Research.

This is due in part to the restriction in social
science research funds in the early 1980s. When AIDS hit as a
result, we had less research into drug use and its prevention,
into sexual behavior and into the methodologies for studying
these topics. We also may have as a result of these and due to a
lack of enrollments in social sciences, a serious shortage of
social researchers needed for doing the research we need.

We have trouble recruiting those that do exist into the
field of AIDS research, I might add. A lot that needs to be done
gets left undone.

Another problem that we have in research that has been
alluded to in the previous panel is that we have to examine and
test some ideas that are controversial in order to protect the
health at this stage, the public health. In Sweden and in
Germany, methadone treatment, for example, is extremely
controversial. In Sweden, in spite of basically not believing in
it, they have doubled methadone treatment, to the point where 30
percent of the heroin users in that society now have slots
available.

140

 

 
 

 

In Germany, they routinely have syringes sold over the
counter and have made sure that pharmacists are actually selling
them. In the United States, controversial issues include syringe
exchanges and giving methadone without supportive services and
counseling.

Here, it is important to understand that although it
is sometimes argued that there are contradictions among various
projects and goals, for example, between methadone and becoming
drug free, or between teaching people how to inject more safely
and entering drug abuse treatment, our experience in prevention
efforts and our research alike show that these programs support
each other. Syringe exchanges, for example, in Europe, do not
reduce treatment admissions. In New Jersey, when they set up a
program to teach people how to use bleach to sterilize works, one
of the major effects of this was people went increasing to demand
treatment, out of drug abuse treatment centers.

We have to do research in controversial areas if we are
going to deal with AIDS. America has always been a country noted
for taking risks, except in this epidemic, maybe not. Federal
agencies are inhibited in sponsoring various kinds of research.
CDC innovative research projects have been hindered by
requirements that local committees approve educational materials,
numerous bodies of the Federal and state governments have called
for syringe exchanges to be tested out. So far, nobody has been
willing to put the money behind it, even in jurisdictions where
it is legal to do this.

We have places in some states in this country that
would like to do syringe exchanges in the context of a funded
research project, but we can't get Federal agencies to fund it so
far, although some are thinking about it.

I have some specific suggestions about research
management. We are reaching a point where we cannot train medium
and high level researchers in AIDS at the rate we need through
normal channels. We need a way to bring established researchers,
good researchers from other fields in social sciences, who have
not been doing AIDS research, into our ongoing projects.

I would propose a senior level equivalent of a post-
doctoral program, appropriate persons might be approached,
associate professors who want to change the area they focus on or
who have sabbaticals. Stipend levels might be on the order of
$35,000 to $50,000 a year. This would let us train people to
become project directors, senior analysts and methodologists and
principal investigators without having to give them line
authority and research grants while they are being trained.

It might also help us to reduce the serious paucity of
minority researchers in this field, which is important when we

141

 

 

 
 

 

are researching behaviors that lead to disproportional infection
of minorities.

Expansions in research funding that have occurred in
the last couple of years have not been matched by funding agency
infrastructure expansion. That means, for example, at NIDA, that
researchers have not had adequate support by staff, because the
staff are overloaded and have much too much to do. In some of my
supportive material, I give you some details on that for NIDA.

AIDS research moves fast and often when we get a
project set up and funded, we discover that it may be a small
project to begin with, and then we discover four months into it
that we need a massive infusion of funds very quickly. There is
no convenient mechanism in Federal funding at this stage to do
that.

We need more top level social scientists in this field
and funding help will do that but also any publicity you can give
and anything you can do to help the prestige of social scientists
who are involved in this research will be helpful in recruiting
such people.

Funding, by the way, in this area, remains inadequate.
NIDA has massively increased its funding and all the rest of it
is still inadequate. The big community demonstration grants
which are essential and critical to research, each one of us is
probably under funded at this stage. We are getting roughly $1
million a year and it is not enough for interventions that have
both an intervention component and a research component. I'm not
criticizing NIDA when I say that. The money just isn't
available.

In addition, the other aspects of research into drug
use and AIDS are not getting adequate funding and we need it
desperately.

The research that has been done suggests the following
interventions to reduce AIDS among IV drug users and their
partners and I guess this is answering the question asked to the
last panel. We need to prevent initiation of IV drug use by
people. We don't know how to do that. We need a lot of
research. We have been doing a little bit. It may become one of
the big fields that needs additional funding effort.

We need a rapid and sizeable expansion of drug abuse
treatment systems. We have capacity for maybe 10 percent of the
Iv drug addicts and considerable waiting time, months, to get
into treatment. We need improved levels not only of funding,
they need space, facilities, staffing, people in this field are
being worked to death, the counselors and such. Research shows

142

 

 
 

 

that better provision of these facilities leads to improved
changes in behavior, less risk taking and such.

Outreach to IV drug users and their partners has begun
but needs expansion and it needs additional innovation on how it
should be done including research, of course. This should
include individual educational outreach. It should include
efforts to promote safer injection, it should include giving out
materials on an experimental basis, and bleach is one, condoms is
another, syringe exchanges has been suggested.

We also need efforts to mobilize the small groups in
the subculture for AIDS prevention and perhaps even to organize
organizations akin to the gay groups from IV drug users and ex-
users and the partners of IV drug users.

Finally, given the extent to which AIDS is
disproportionately impacting blacks and hispanics, we need
special programs that involve minority community organizations
and institutions.

This is the end of my presentation. If you want to ask
me about evaluation of what is effective in the way of
interventions, I will welcome that.

[The prepared statement of Dr. Friedman follows in the
Appendix. ]

DR. CRENSHAW: Thank you very much.
Dr. Karen Hein.

DR. HEIN: I am Dr. Karen Hein. I ama physician
specializing in adolescent medicine and I am the director of the
nation's first adolescent AIDS program, at Montefiore Medical
Center in affiliation with Albert Einstein College of Medicine.

In my few moments, what I would like to discuss is the
impact of the epidemic on adolescents. Why adolescents? Which
adolescents? And what to do for and about adolescents?

I will give you data to support the following three
points:

1. We have the opportunity to turn back the clock to
1981, to learn by what we have done and what we haven't done,
about what we could do for adolescents.

2. We are at a unique point in this epidemic. Only

about one percent of the case of AIDS are in adolescents, but
many more are in the direct path of this epidemic.

143

 

 

 
 

 

3. There are critical differences between adolescents
and children and adolescents and adults. It is these differences
that we have to focus on in our planning in the next year or two.

To help in this planning, I want to briefly review a
profile of the epidemic in adolescence to say that there aren't
many cases, but there a few factors that could make all the
difference.

First of all, of the 500 cases in young people ages 13
to 21, remember that these are AIDS cases. The latency period
may be on average about seven years, with latency as long as
12-15 years, so that many cases of people in their twenties are
really people infected in adolescence.

Secondly, we don't know much about the prevalence of
HIV infection in adolescents. Some information from the Job
Corps, from the Peace Corps and the military data do suggest that
in epicenters where HIV infection has spread to other
populations, that the adolescents are involved at this point.

Lastly, rates of sexually-transmitted diseases other
than HIV are very alarming in adolescents and continue to be well
into the eighties.

If I may have the first slide, we'll now look at a
profile of the epidemic among New York adolescents to see what
the relevant factors are that we can learn for the rest of the
nation.

[Slide. ]

Here we have a pie graph showing the breakdown by risk
group for 114 cases of adolescents reported to the New York City
Department of Health.

The important features are, first of all, that the
largest group are in fact the male homosexual and bisexual
adolescent -- again 13 through 21 years of age. However, this
piece of the pie, 44 percent, is actually a smaller percent than
the nation as whole.

The second piece, the IV drug abuser accounting for 23
percent of cases in adolescence, is again smaller than the nation
as a whole and somewhat comparable to adults in New York.

Most important, however, is this wedge -- the female
partners of high risk males, accounting for 11 percent of
adolescent cases. This is far higher than adults. If we look at
the females alone, this accounts for 42 percent of all the female
adolescent cases in New York.

144

 

 
 

 

Lastly, the pie piece that represents the blood
product recipients again differs in New York as compared to
teenagers in the nation. This is eleven percent of the pie in
New York, but if we look at the nation, the young hemophiliac
male, the 11 to 17 years old in the nation, this piece of the pie
would account for 80 percent of such males. In New York City
many, many more of the cases are related to behavioral factors.

(Slide. ]

Now let's take a quick look at the breakdown of New
York AIDS cases in children, adults, and adolescents to make the
points about the differences in these three age groups. Again,
the male homosexual or bisexual is a large piece of the pie, but
adolescents are somewhat less -- this is a less common risk
behavior than in adults. As far IV drug abuse goes, the
majority of parents of youngsters born with HIV infection are of
course IV drug abusers. Again, the adolescent and adult
populations are not too dissimilar one from the other.

But here is the biggest group. In the nation, only 4
percent in adult are attributed to heterosexual spread, but a
much higher percent in adolescents and, again, blood product
recipients for the nation -- adolescent males, largely
hemophiliacs, but in New York City this is not a very prominent
reason for HIV infection, at least as reported in AIDS cases.

Now if we are going to talk not about New York City
adolescents because what do they represent vis-a-vis the rest of
the country, I am going to show you a conceptual model to help
you think about all the adolescents in the country, some 25
million between the ages of 13 and 19. They represent many, many
different kinds of adolescents. This is a conceptual model that
I have developed to help you understand the degrees of risk among
the adolescent population, from those teenagers at no risk to
those who are at immediate risk or who are already infected.

The circles do not represent actual numbers of
teenagers again, but are in relation to the degree of risk. In
the inner circle we have the teenagers who are not at any risk at
the moment. They tend to be young, virginal, live in a place
where the virus isn't, have not received a transfusion and don't
use IV drugs.

Perhaps in the question-answer period we can -- I have
some slides about the rates of sexual activity among adolescents
in the country. But at any rate there are still issues, even for
this group. They are three.

First of all, they may be the "worried well." How are
they going to live and grow up in an atmosphere of concern and to
not have undue concern and anxiety.

145

 

 
 

 

Secondly, they need information about casual contact,
so that they can develop sexually and emotionally healthy in ways
that don't put them at risk for this epidemic.

Lastly, they need support for their current sexual
decision, namely abstinence.

In the next group we have those teenagers who are
sexually active but not at risk at the moment. That may be
because they are living in a place where the virus isn't --
because at the moment geography is destiny. Still there are
issues for them -- the fact that they can't know their partner,
that they might want to reconsider their sexual decision, and
lastly that contraceptives in general are important for them and
condoms in particular. They are separated by a dotted line from
this group of teenagers at risk right now, many of whom have been
infected already.

These teenagers can be infected from any one of eight
potential sources: adults, homosexuals and bisexuals, IV drug
abusers and their partners, or some teenage gay males, by sexual
teenage drug abusers or teenage partners.

In our program we now have examples of every one of
these circles. Decisions for them include the decision of
whether or not to be tested, to know the serostatus of their
partner, the need for condoms, reconsideration of their sexual
practices, and -- for the females -- to decide to continue or to
become pregnant.

Currently there are very few to almost no services
that are specifically geared to help the adolescents really in
any of these categories, but particularly in the outer ring. In
our program, the first six HIV positive teenagers had 50 sexual
partners, one of them had none and one had 28, to give you a feel
for the range of what infected adolescents look like now.

I would like to now conclude with some of the recent
responses to the challenge posed by adolescents in this epidemic
~- if I can have the lights up.

I am going to mention by name only, but in the written
material there are descriptions of nine responses, all of which
can be viewed in the sense of a recommendation.

The first has to do with network. There are two task
forces that exist so far in the country on a volunteer basis, one
on the East Coast and one on the West Coast, to specifically
bring together agencies in health, education, and direct services
for teenagers.

146

 

 
 

 

_ Our own adolescent AIDS program again is the first, but
hopefully ‘will be followed by others to spread the knowledge and
experience and care for adolescents around this country.

Secondly, the use of adolescent resource groups. Focus
groups have been used by the health department in this city and
others to screen and evaluate educational material. There have
been hotlines developed by teenagers for teenagers, and peer
counselling models where young people are used to help to educate
and help change behavior in other youngster have also been
developed and are not currently -- we don't have information
about their effectiveness in AIDS but we do on their
effectiveness in some other chronic illnesses.

Educational materials, books and pamphlets and videos
and certainly curricula are coming out at a very impressive rate.
However, cost, distribution problems, access problems and again
the lack of evaluation are very pressing concerns.

Fourthly, analysis of available data, as I have shown
to you, drawn from the Centers for Disease Control and the New
York Department of Health, are available for teenagers. But if
we lump them with children or adults we are going to miss some of
these key differences that could help us in planning,.

Fifthly, surveys of AIDS knowledge, attitudes and
beliefs have been conducted in a pilot way, particularly in four
communities -- New York, San Francisco, L.A. and Boston. These
can become the NIDAs for longitudinal studies and for more
widespread studies.

Importantly, to link my comments with the former
panel, the best questionnaires are those which include questions
about behavior, not just about knowledge, attitudes and beliefs.

Sixthly, condom distribution schemes for adolescents
are just beginning to be planned. Mass condom distribution
campaigns have been promulgated here in the City through the
Major's Office of Adolescent Pregnancy. But other such
distribution campaigns have existed for adults in other parts of
the nation.

We don't know very much in the seventh recommendation,
about what HIV infection looks like in the adolescent population.
I have showed you AIDS cases. We don't know about the
progression of this illness in adolescence, the percent of
asymptomatic versus symptomatic co-factors, whether they'll look
like little kids and die quickly, often of bacterial common
infections or like the adults with rare cancers. These are
unanswered questions at this time.

147

 

 
 

 

Eighthly, there are some new funding initiatives, but
they are buried. NICHD, NIDA, NIMH, MCH -- all may have funds
available for teenagers but there is no way to report to you how
much money is available or just where, because adolescents are
usually lumped with children or with adults.

Lastly, the ethical and legal issues are perhaps the
most pressing at this point in time and something that the
commission should embrace and carefully weigh and consider.
There are mandatory testing policies in place now in the Job
Corps, the Peace Corp, the military and for dependent minors of
families in the State Department who are going overseas.

The impact of these policies has not been looked at,
but there are many instances now of a terrible fallout of these
mandatory testing policies on the lives of teenagers. For
example, military recruits in the City of New York who were found
to be positive are told that they are positive, not enrolled in
the military, given the number of the New York Department of
Health hotline and that is it. There is no attempt at this time
to link them with appropriate services to help them or their
family.

In this ethical and legal dilemma, the whole question
of parental notification of results or parental requirement for
testing are issues that really need clarification.

So in conclusion, the history of the AIDS epidemic's
impact on adolescents is a very brief one in that this commission
is one of a handful of places in which the adolescent issues have
been aired. The IOM report made reference to adolescents, the
Surgeon-General's workshop in April, the June House Select
Committee hearings on Children, Youth and Families -- but these
are it.

In March there will be a National Invitational
Conference to focus on the issues of AIDS and adolescence. But
we are only at the beginning of learning about the impact of this
epidemic on adolescents. If we don't consider their special
needs, then we may repeat the mistakes that we have made that
have led to the situation in the adult male homosexual, IV drug
abusing community.

The next two years will make all the difference in the
lives of our young people. Thank you.

{[Applause. }

(The prepared statement of Dr. Hein follows in the
Appendix. ]

DR. CRENSHAW: Thank you very much.

148

 

 
 

 

Dr. Coates?
DR. COATES: Thank you.

In addition to what I have already told you I would
also like to mention that I sit on the National Academy of
Sciences Committee on AIDS and Social and Behavioral Research and
we will be issuing a report in October. Hopefully, many of the
recommendations coming out of that committee will dovetail with
many of the recommendations coming out of this committee.

I also speak here on behalf of the American
Psychological Association, which, as a member of the association
I can say I am extremely proud. It is one of the few
associations -~ one of the few professional associations that
responded early and loud with attempts to deal with the AIDS
epidemic, both within its membership and on behalf of its
membership to other important bodies.

I guess I would like to start off by saying -- and I'll
try to be mercifully brief and not read my testimony, which
contains the major substance of what I want to say to you. I
think I would like to start off by saying that I think that the
most important agenda in behavioral and social research with AIDS
is prevention.

Now if one can take that as a given, one has to think

that many things in life are crazy. "Crazy" is not a word that I
like to use, for example, around the National Institute of Mental
Health -- they are kind of sensitive about that word. But it is
crazy that this Commission is sitting here in 1988. It should
have been convened with regard to the AIDS epidemic in 1983 or
1984. But it is even crazy that it took an epidemic like AIDS to
bring a Commission like this together.

As you have heard, many, many, many, many times over
and over and over again, AIDS is only the last in a series of
sexually-transmitted disease epidemics that this nation has faced
and it has been a very serious, serious health problem that we as
a national have failed to come to grips with.

Herpes, Hepatitis B, syphilis, chlamydia -- and you can
go on down the line -- along with unplanned pregnancy, unwanted
pregnancy and teenage, which have been with us for a long time.

So therefore my first recommendation to this committee
is that it recommend loud and strong that the federal government
-- and the group of the federal government that I am most
intimately interested in, and that is the research arm -- never
again allow sex research to be put under the table.

149

 

 
One of the biggest advantages of the AIDS epidemic is
that sex again has come out of the closet and we can talk about
things like condoms and anal intercourse and even vaginal
intercourse in public. There needs to be in place a permanent
mandate to the National Institutes of Health or to ADAMHA that
they maintain a sharp focus on sexual research, much as we would
not allow them to go out of the business of doing cardiovascular
research, much as we would not let them go out of the business of
doing cancer research, we cannot let them go out of the business
of having a coordinated and concerted program of sexual behavior
research.

Now, still continuing my theme, and that is commenting
on the craziness of the world, I think another institutional
establishment issue that needs to be addressed is that no one on
your committee, and I respect your credentials, is a behavioral
scientist. We have seen this over and over and over and over and
over again. And I am not just sort of pulling for my own kind --
but if these are behavioral issues, why isn't there behavioral
science expertise on your committee? I am sure we could look
through the ranks of the PHS committees.

In the early days the CDC convened a consensus
conference on the issue of antibody testing. Behavioral
scientists were invited only after the APA sat on its hind legs
and screamed, "This is a behavioral issue."

There was a planning meeting on the issue of condom
efficacy at the NIH. There was one behavioral scientist among 12
people. This is another institutional issue that needs to be
addressed -- that behavioral science and behavior change
expertise needs to be included at the highest levels and the NIH
and ADAMHA -- the brain and the rest of the body if you will --
needs to learn how to talk to one another. We always have
difficulty on a personal level; I guess there's no reason to
believe that the government wouldn't have the same problem. But
it is an absolute necessity.

Now with regard to the issue of prevention, I have
already made my first recommendation to you earlier, and that is
that the national priorities need to be changed. It is critical
and essential to spend as much or more money on AIDS prevention
and intervention research as on biomedical research.

Dr. Bowen, in an article in The New York Times last
Sunday, indicated that it was his opinion that the spread of the
epidemic, particularly among heterosexuals, was not a major issue
and not a major problem. Myself and most scientists that I talk
to wonder if he has data that the rest of us don't have. We
simply don't know. And in the face of that lack of knowledge we
must continue with prevention efforts for that reason, for the
reason that I mentioned -- that this is not the only

150

 

 
 

 

sexually-transmitted disease that we are interested in, and
because we as a nation have taken it upon ourselves as one of our
fundamental values that we have concern for our international
neighbors.

You know, it is ironic that one of the policies that
the Administration wanted to put in was testing of immigrants for
antibodies for HIV. At least in terms of reported cases of AIDS,
we are the reservoir of disease.

[Applause. ]

We should perhaps think about helping people not to go
out with the disease, at least not to carry it into other
populations. Mexico, South America, have yet to grapple with
this awful problem. We know what is going on in Africa and what
may happen in the South Pacific.

_ So I think for these reasons we need to carry ona full
and complete program of prevention research.

I think there are two interesting and important
indicators on the potential spread of infection among other
populations. One is the system of surveillance that is now
being done in several major cities with regard to testing blood
for antibodies to HIV. Of course the figure in New York is about
1 in 60. :

The other interesting set of data are the armed forces
recruitment data, where they are looking at monthly trends in HIV
antibody among individuals who are coming to the armed forces
recruitment centers to seek entry into the military. There has
been no change in those trends -- and this is in the CDC Report
to the Domestic Policy Council. There has been no change in
those trends since the beginning of that surveillance system over
a period of about 18 months and that is, they continue to find
that about one and a half in 1000 are infected. This is reported
in the July issue of the New England Journal of Medicine.

Interestingly, in three boroughs of New York, in Essex
County, New Jersey, in Washington, D.C. and San Francisco the
prevalence is one in a hundred -- and that hasn't changed over
time.

The male to female ratio is 1:1. The Black to white
ratio is two and a half to one. I submit that we have a very
serious problem here and one of the recommendations I am going to
make is that the Department of Defense, because it has discovered
these individuals and, as Dr. Hein said, they are given a
referral number to the Departments of Health, that we conduct a
very serious set of research programs on these individuals both
to determine their risk factors, to determine their behavior once

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they are tested for antibodies, and to help them deal with this
awful information.

Given that I am such a keen advocate of prevention
research, I guess the major question is, "Can we achieve the
changes necessary to stop the spread of the epidemic?" It is an
issue of impact effectiveness. Can we get enough people to
change enough behavior over enough period of time so that in fact
the spread of the infection is limited?

I am sure you have heard about the San Francisco
experience, but I think the experience there is very compelling
and our experience shows us that it can. There are four
behavioral studies, and all of them point to the same conclusion,
and that is somewhere between six and eight percent, depending on
the sample, of the men in those samples continue to practice
unprotected receptive anal intercourse.

Anal intercourse was a very favorite activity of the
gay population. When we began our baseline studies, 50 to 70
percent of our samples were practicing that activity. This was
in the very earliest days of the AIDS epidemic. This is an
incredibly remarkable change and suggests that perhaps it can be
done elsewhere.

I am sure, as you have heard from the San Francisco
Men's Health Study, that the rate of new infection at least in
that one study is less than one percent.

The other important issue with regard to this unique
population -- and then we will talk about how it might be
generalized to other populations -- is that these changes are
being sustained over time. Believe me, having devoted my career
to health behavior change, this has never happened before.

I was asked to be interviewed by a reporter from Der
Spiegel and I couldn't fit him into my schedule. I said "Come on
over to my house at night. I will give you a glass of wine. I'll
get some German wine. We'll drink, you know, and you can
interview me."

So he came in the door -- he smelled of cigarettes.
And so we got into my rap and he said, "Well, how can anyone --
yes six to ten percent is remarkable -- but how can anyone engage
in a behavior that is so lethal when they know the consequences?"
And I said, "Well, let me tell you something. The most
preventable cause of morbidity and mortality in the United States
today and in Western Europe is tobacco." It is responsible for
some 300,000 to 500,000 deaths annually and, as I am sure you
know, is related to heart disease, all kinds of cancers,
osteoporosis and even wrinkles. Even though it causes wrinkles,
people still smoke.

152

 

 
 

The Surgeon General of the United States, Luther
Terry, published the first Surgeon General's report on smoking
and health in 1964 -- 55 percent of men smoked. How many men
smoke today? Between 30-35 percent. So the changes observed in
the gay population are remarkable, incredible and need to be
studied.

I was once called by a reporter -- a producer rather --
from "20/20." This was a couple of years ago. She said to me,
we are interested now in looking at the heterosexual angle and I
am interested in asking you what kind of data that you have. I
said, well, the studies I am doing -- and I should have put this
in context; I am from the Centers for AIDS prevention research at
the UCSF and we have several studies with many populations but at
that point we were primarily studying gay and bisexual
populations -- and she said, well, we are really not interested
in the homosexual angle, we are interested in the heterosexual
angle.

I wanted to ask her how heterosexual angles differed
from homosexual angles but I decided not to. I asked her instead
-- or I told her instead -- that AIDS is fundamentally a human
disease and the variables that control behavior for one group of
individuals probably can be looked at and thought about for their
potential application to other groups of individuals.

Now what about my three specific research priorities?

The first question and the burning question I am always
ask is why do high risk individuals continue to practice high
risk behavior? And it is important to put this into context. We
want to segregate sexual behavior and we want to segregate IV
drug using behavior and somehow make them special. The fact that
so many of our men change suggests that probably the variables
that control many other health-related behaviors control these
behaviors as well.

We have been doing in-depth studies, and why do men in
our samples continue to practice high risk behaviors? We know
that those who are younger have a harder time changing their
behavior. We know that those who are Black have a harder time
changing their behavior. We know that those who receive antibody
testing under conditions of confidentiality, anonymity and with
appropriate pre-test and post-test counselling are assisted in
changing their behavior. We know that there are certain personal
characteristics -- a feeling of personal susceptibility, a sense
of efficacy -- we know that those individuals change behavior.

So the second recommendation I want to make is that the
government, the NIMH needs to fund additional studies to describe
the meanings and the characteristics of sexual behavior and IV
drug using behavior, especially comparing those who have failed

153

 

 
 

 

to change with those who have changed, so that we can understand
better how to intervene with these populations.

"Meaning" is a very important term and let me caution
you against the use of one term and that is the term
"promiscuity." We are really talking about multiple partner sex.
If we go into another culture, the Maori culture of New Zealand,
multiple partner sex is the norm and people are not homosexual or
bisexual or heterosexual, they are sexual. They enjoy a natural
reality and I think we need to be careful about our language
between we need to truly understand various populations.

Now of course descriptive studies are not enough and I
think at the same time that we are engaging in a program of
descriptor studies, we need to engage in a concerted program of
intervention studies.

From our cardiovascular prevention research studies, we
know some of the elements of behavior change. We know that
people need to have information. They need the information. It
needs to be personally appealing. It needs to be in language
they can understand.

People also need skills and this is where education
generally breaks down. If you really want someone to engage in
protected sex, then they need two particular kinds of skills and
this is an issue we are going to have to face. This is a hot
political issue. They need to know how to use the condom and
they are not easy to use. And they need to be able to engage in
the complicated social skills to negotiate the use of that condom
and we have to be willing to teach then.

The third thing they need -- the third key element of
education programs -- is specific attention to community norms,
methods for shifting the norms of the community so that when one
individual comes in contact with another individual they both
expect that they are going to want to do whatever they want to do
safely.

Therefore the third recommendation that I am making is
that the NIMH in collaboration with other relevant agencies
undertake controlled studies of the efficacy of community
intervention programs in reducing high risk behavior. This is
clearly what happened in San Francisco. It was a community based
program that included strong leadership from within the gay
community. It used up-to-date, state-of-the-art market research
techniques to identify messages and communications channels. It
used a variety of communications channels, gay and straight
media, face-to-face, health professionals' education, workplace
education -- whatever avenues could be used to reach the
population.

154

 

 
 

 

It was not afraid to teach skills. It was not afraid
to use specific techniques to change the norms of that community
and it involved broad scale, grass roots participation.

Now the final set of studies that I want to recommend
is at the National Institute of Mental Health and it needs help
in having the nerve to do this: In collaboration with other
relevant agencies support a coordinated set of studies aimed at
programs with high risk populations or avenues of interventions.
What I am suggesting is a program that has been used very
successfully by the National Cancer Institute. They are not
afraid of smoking despite the tobacco industry. We can't be
afraid of sex despite our squeamishness. That is, this
coordinated set of studies -- that they fund five to ten
investigators to work on specific populations, bring them
together and help them move their studies along. The populations
that need special attention are still gay and bisexual, who
comprise 66 percent of the cases of AIDS and 80 percent of the
estimated individuals who are infected with HIV but not yet
diagnosed with AIDS. That is from the CDC Report to the
Domestic Policy Council.

Special emphasis needs to be given to minority gay and
bisexual men -- there is one study -- one study -- from the NIMH
focused on Black gay men -- that is unconscionable given their
high rate of disease -- and to homosexual youth; IV drug users
and their sexual partners; adolescents -- especially minority
adolescents; persons presenting for treatment at sexually
transmitted diseases clinics; individuals identified as positive
for antibodies of HIV at the armed forces recruiting centers;
ethnic minority women; and prostitutes and others in the sex
industry.

I propose that programs of research be developed in
each of these areas. A minimum of five to seven studies should
be funded to reflect national distribution. The investigators
should be encouraged to request money for at least five years and
the best methods of science should be employed to plan the
studies and to evaluate outcomes.

This total program is cheap, believe me. It will cost
around 200 million dollars over a 7-10 year period of time. The
initial start-up cost for the NIMH would include a $60-70 million
allocation for FY89, some $10 million to $20 million more than
they are requesting. I think it is important. I think it will
address AIDS. I think it will address many other problems.

Finally, we all recognize that we are working in a
delicate arena. We are not working with smoking or exercise or
weight reduction where people can agree on the kinds of changes
that need to occur. We are working in the area of sexuality and
we all have deep feelings about that. I think we need to provide

155

 

 
 

 

an agenda of research and philosophical discussion where we can
begin to come together on some of our deeply held value
differences with regard to sexuality itself, and with regard to
appropriate programs and targets for intervention. The issue is
scientific. The issue has to do with the health of the nation.
The issue is also moral and we need to have forum for resolving
this problem.

Thank you.

(The prepared statement of Dr. Coates follows in the
Appendix. ]

DR. CRENSHAW: Thank you, Dr. Coates. We have a few
moments for questions, not nearly enough, as usual. But I want
to highlight the importance of the content and type of material
that has been shared with us today.

We are looking, perhaps for the first time, at really
forceful intervention and prevention techniques and it is quite
different to talk about education and its importance and
prevention, and to implement and to actually do something,
especially for our adolescents, who are now an apparently low
risk group but an ultimate target for sexually-transmitted
diseases.

So I would like to begin the questions with Dr.

DR. LILLY: I will try not to be hoggish, but I have a
great many questions for each of the panelists.

Dr. Carnes, I was surprised at one datum in one of your
slides that suggested that three percent of some group of
so-called sex addicts had developed AIDS. Given the association
between sex and AIDS, I found that surprisingly low. I am also
wondering, is the criterion for sexual addiction merely
numerical?

For Dr. Friedman, I would like to know -- do you know
of research relevant to the question of whether needle
availability actually encourages in any sense whatsoever drug
use?

For Dr. Hein, can education in schools adequately be
effective in reducing HIV infection? Is the school sufficient
to the need? For example, in New York City, where there is at
least to some extent education on the subject, do you have an
evaluation of that?

Dr. Coates, one thing you said quite startled me. I
would have thought exactly the opposite, but again this is a
subject that I know nothing about. You said that younger people

156

eer ete Fed wt ae ah | ood Ete ROO cute ST em fe eh are oe ae a Ole

 

 
 

 

and Black people have a harder time changing their sexual
behavior than older people. I would have thought it would be
exactly the opposite.

And then, also for you, given the fact that there is a
significant portion of the population that just doesn't want sex
discussed at all, again on the theory that if you discuss it,
people are going to rush out and do it -- how do we cope with
that attitude?

I rest.
DR. CARNES: Can we take them in order?

DR. CRENSHAW: Go ahead, and I think we are going to
have to depend on a lot of supplemental written information for
this, so that all our panels can ask something.

Go ahead.

DR. CARNES: I think that makes sense. The question
about the three percent -- the point that I was making about it
is that that particular study, which has about 400 people in the
sample -~ were people who had entered recovery programs for their
sexual addition five to seven, eight years ago. So the point was
that even in that sample we had three percent who had AIDS, even
though their sexual behavior had been modified significantly over
the last five to eight years.

What I was trying to demonstrate with the slides is
that how terribly at risk these people are. One of the things
that we need to take a look at it are alcoholism units, our
eating disorder units, to train people to help identify the
people who are coming in now, so we can get a different baseline
so that current statistics are available. Our hunch is that it
is extremely high and I maybe didn't make that as clear as I
could.

DR. LILLY: Thank you for that.

DR. CARNES: The second criteria question about what
does it take to -- obviously, as it was in alcoholism, it isn't
how many drinks you drink -- it is not the same issue. There is
a very elaborate diagnostic framework both for outpatient,
inpatient and a number of different ways of looking at it from a
private practice and I would be happy to supply the committee
with those kind of diagnostic criteria.

DR. LILLY: Thank you.

DR. FRIEDMAN: On whether or not needle availability
encourages IV drug use, there have been no comparative area

157

 

 
 

 

studies, for example in looking from city to city to see about
availability and IV drug use. That would be a useful thing to
have happen.

On the other hand, this has its greatest policy
relevance perhaps to syringe exchange proposals. On that there
have been studies on the effects of the Dutch syringe exchange.
They are not definitive yet, but the Buning study indicates that
it leads to decreased needle sharing and that there is evidence
in the Buning and in the Van de Koeke study that there is lower
frequency of IV drug use among the people attending and getting
syringes through the exchange than among the people who do not
come to that.

Finally, the other way in which this could impact is
in terms of does it decrease treatment admissions. The theory
might be that if you can get sterile syringes, you are not afraid
of AIDS and therefore you don't go for drug treatment.

There is no evidence of this from any of the many
countries that now have needle exchange programs and the study as
I mentioned before of the Amsterdam Exchange decisively show that
there at least there has been no such negative impact nor any
influx of new IV drug users in large numbers.

DR. HEIN: To answer your question about the
curriculum, curriculum is a good first step. Schools are where
most kids in this country spend their days. It is fine.
However, who is teaching the curriculum and what is the content?
Do teachers have the time? Do they have the sensitivity and
knowledge? What about parents? They have the responsibility.
Do they have the non-judgmental ways to present the information.
Friends? They certainly have a powerful influence. Do they have
the judgment or the knowledge? Doctors -- from the question
that you submitted earlier? Doctors: There is a network of
adolescent clinics to help young people in a variety of health
issues. These and the school-based clinics are obviously good
ways to begin.

So the answer to your question: There is nothing
wrong with school curriculum. Many of them -- most of them
haven't been evaluated, but why should we stop there? We should
only start there. I could anticipate Dr. SerVaas's question from
the previous panel on rates of sexual activity in teenagers. If
we could have Slide No. 6, a quick answer to your question on
rate of first intercourse among teenagers in the country.

DR. LILLY: I am not sure that we still have the
capacity to show that slide, at this point --

(Slide. )

158

 

 
nT

DR. HEIN: Okay, in your materials then, in the article
on “AIDS in Adolescents," there's for the nation, basically
showing you for rapes among White and Black adolescents, ages 15
through 19 in three different sample periods in the 1970s. The
point is that the rates went up, that they are high. Eighty
percent of Black females in urban areas have had intercourse by
19, 60 percent of females. The biggest increase were among the
White female.

And the next slide -- what about various population of
adolescents?

(Slide. ]

Here we have three curves, for a detention center (New
York's only through the 1970s); urban group homes; and the
national survey of Sorenson. Now for all young people who have
had intercourse by 19, this shows what percent at different ages,
and to make the point, among the detention center population, the
average age of first intercourse was 12. For the national as a
whole, the average age of first intercourse for people who had
had intercourse by 19, was around 16 -- 15/16.

So, yes, early intercourse among certain groups and
certainly sexual practices among adolescents need to be
understood and then adolescents helped with knowledge,
information, and most importantly let's not leave out services.

Services: we talk about adolescents as if we could
only educate them our job is done. The point is the virus is
there and we have to help the people that are already infected
and their partners in curbing this epidemic.

DR. COATES: So, Dr. Lilly, it looks like everybody is
rushing out and doing it anyway, so I think the appropriate
answer to your question is that if they are rushing out and doing
it under conditions where we are afraid to talk about it, what
might happen under conditions where we really can talk abut it?

I submitted to the committee with my testimony a very
lovely study published -- Murray Vincent, Dr. Murray Vincent was
the senior author -- published in JAMA in the summer and I think
it is an excellent example of what can be accomplished. This was
in South Carolina and they engaged in a two-year community
intervention program analogous to the kind of program that I
suggested happened in San Francisco. They were able to cut the
number of teenage pregnancies by one-third of the original rate,
and compare it to adjoining counties where this didn't happen.
This involved a process whereby church leaders, family leaders,
workplace leaders, and school leaders got together, dialoqued
about the appropriate objectives, equipped teachers and parents
with the ability not only to talk about these things but also to

159

 

 

 
 

 

 

teach skills, so that people really understand how to negotiate
these very complicated social interactions.

The Centers for Disease Control, as part of their
education programs, have conducted extensive focus groups with
adolescents. Their experience probably would fit most people's
here. If we were to take a poll in this room of everyone's first
experience with intercourse, I think many people would say, well,
it just happened. Now that doesn't take into account the fact
that we may have fantasized it for years before it "just
happened," but it points to the fact that people, when they are
beginning to engage in something that we as a society consider a
very important activity and a very important way of relating to
another individual, we fail to equip people for the ability to do
that.

What that means is that we need to start much younger,
both with information about sexuality but also with the social
skills. People don't have to have sexual relations if they don't
want them. They should have the social skills and the abilities
to deal with those things. That takes education.

So I guess I would say that the data really point to
quite a contrary event. I would think we could delay onset of
first intercourse and that in fact may be an important event
because of the STDs and the unwanted pregnancies that are
associated with that.

If we were willing to bite the bullet and start
educating in an appropriate way, people would have the ability to
deal with it. We wouldn't say, well, gee, if we talk about
driving cars, people are going to go out in the street and start
driving cars, so we better not talk about it; let's just let
them sort of do it when they are ready, it would be a worse
disaster than it is.

Why don't we deal with this very important arena ina
sensible way?

Now in terms of resolving those cultural values, I
think it is going to take dialogue. These are deeply held values
and I think we need to stop sort of firing volleys across the
chasm of our heterogeneity and think about ways of bringing
groups together to think about this is a serious way. I know of
no other way or admit that in fact we are a heterogeneous values
that we can tolerate.

DR. CRENSHAW: Dr. Coates, you just made a very
important point that I think is usually not in focus and that is
giving adults or adolescents knowledge and information without
teaching them comfortable and workable social skills to

160

 
 

 

implement them with is leaving out the major’ step that enables
them to practice what you are preaching.

I would like to ask especially Dr. Hein to send me in
writing your best recommendations for how we can access and
highlight attention to the adolescent and teenage population,
because one of the things that I am simply committed to try to
accomplish on this Commission is to reach that population as all
the others while they are still low and before we are reacting
like we have to all of the other disasters.

Dr. Walsh?

DR. WALSH: I do not have any questions. I am just
closing with a very brief comment, and that is you all are
preaching to the choir when you tell us that we need behavioral
science research. We are all in favor of it. It simply
provides us again with the problem of priorities, of what we are
going to recommend, and I can assure you that we are going to
take that into consideration.

In regard to the membership of the Commission,
remember, none of us campaigned for this job. If everyone who
should be on it could be on it or would be on it were on it we
would have a commission as big as the Congress and then we would
only talk to one another and we wouldn't come to any conclusions.

This way, at least we are able to come to all of you,
all of the groups -- the high risk groups, all of the people with
varied skills -- and pick your brains the best we can. And
believe me, we are trying to do that job as honestly as possible
so that we can give you a real fair shake with our
recommendations

DR. COATES: We look forward to the concert.
{Laughter. ]
DR. CRENSHAW: Mr. Creedon?

MR. CREEDON: I would like also to thank the panel
members for very interesting material.

Just one question to Dr. Hein, a simple question. I
got the impression you were saying the adolescents you want to
target are from age 16 on. I would think it would be a lot
younger than that.

DR. HEIN: No, I didn't mean to give that impression,
because again with the age of first intercourse, what is it and
with --

161

 

 
 

 

MR. CREEDON: It has to start earlier --

DR. HEIN: -- understanding of sexuality certainly
preceding puberty. We are really talking about older children as
the Surgeon General suggested, in the age range of about eight on

up.
MR. CREEDON: Okay, I agree. Thank you.
DR. CRENSHAW: Dr. SerVaas?

DR. SERVAAS: I just had one quick question. It is: on
your adolescents, it was very disturbing to me that we didn't
have physicians to whom to refer these AIDS-positive adolescent
children. Would you tell the children they are positive for the
HIV infection and then give them a hotline number? You really
don't have --

DR. HEIN: That is the current procedure for all of the
military recruits in this country. Now we would hope that as a
result of the commission and other caring people, that this will
change. The military has to define their area of
responsibility to do screening and caring for the people who are
enrolled, not for the recruits. So certainly here is a very good
example of the kind of quick response the commission can make to
help again the rates among the military recruits and adolescents
in certain parts of the country, who as Dr. Coates has said, are
incredibly high.

DR. SERVAAS: And then how many adolescent cases do you
have?

DR. HEIN: Well, again, it depends on how you define
cases. Our first HIV positive six kids had 50 partners. Do we
include them all in our cases or not? So little do we know about
the rates of HIV positivity among adolescents right now that that
is not a question that is easily answered.

Certainly we at the moment again have opened our doors
to any high risk adolescent to an HIV positive or their partners.
But very few people have the resources, time or skills to be able
to encompass this kind of counselling for adolescents. There is a
network there of adolescent health clinics, of doctors
comfortable with adolescents but they have not been freed up as
was suggested for their retraining and re~tooling to enable them
to do the kind of counselling and followup that is now required.

DR. CRENSHAW: Dr. Lee, I understand you have a quickie
to wrap up us with.

DR. LEE: To reassure Dr. Coates -- when we organized
our study and our report, in the very beginning, one of the

162

 
 

 

places we went was to the Institute of Medicine, and we are in
very heavy discussion with Dr. Roy Widdus, Dr. Heather Miller,
and the ongoing behavioral modification conference that they have
been holding there, and we will be privy to their report.

For Dr. Coates, a fascinating group of people very
pertinent to our study, that population you have identified, and
I notice your background is extremely unusual and I might ask Mr.
Creedon to take note of your background because I would think it
would be very helpful in doing polls and statistical evaluations
of sexual behaviors in the population.

DR. CRENSHAW: I'd like to thank all of you very much
for coming and speaking with us. I am sure you feel as
breathless as we do in terms of the ground to be covered and the
opportunity that we had. I think it is clear that we need
baseline data. I think it is clear that we need behavioral
research and behavioral intervention programs with evaluations
that are adequate to measuring the outcome of these efforts. I
hope that we will have this just as a beginning and not as a
completion of dealing with the issues, of understanding them and
of coming to grips with them as I think we must do.

Thank you again very much, and thank you to the
earlier panel, whom I see still with us.

[Applause. ]

(Whereupon, the meeting was concluded. ]

163

 

 
 

 

APPENDIX

 

 
 

 

Opening Statement Thursday, Feb. 18, 1988

Admiral James D. Watkins (Retired)
Chairman
Presidential Commission On the HIV Epidemic

Good morning to our distinguished guests and panelists, to
my fellow Commissioners, and to our audience.

Today we begin our hearings on AIDS research and drug
development. Research and drug development is the last of the
four areas we identified as topics to be addressed in our interim
report, which we will deliver to the President in about two
weeks.

Research and drug development is a complex arena with many
unanswered questions. It stimulates controversy and impassioned
discussion among all of us, and reflects the fear of a society
confronting a fatal disease for which there is no known cure.

Last November two PWAs appeared before our Commission in
Florida to talk about the need for further research and drug
development. Unfortunately those two PWAs, James Sammone and
Patrick Haney have since died of AIDS. I have talked with the
fathers of these two young men who have, in turn, dedicated their
lives to furthering AIDS research. It is on behalf of persons
like James Sammone and Patrick Haney that we begin our work
today.

Today we will hear the frustrations endured by those seeking
drug therapies when so few drug therapies are available. We will
examine the drug development process and the drug approval
process. We will hear from people divided in their opinions
about what our society has done and what our society should do to
expedite the development and availability of drugs for persons
infected with HIV.

Our witness list includes all parties involved in the drug
development process: persons infected with the HIV, the basic
researchers, the regulatory agency responsible for approving new
drug treatments and the pharmaceutical companies. Their research
efforts will benefit all of us, in terms of both prevention and
treatment.

The witnesses who will speak to us represent the best and
the brightest in research and drug development. They also
represent the essential leadership which must be brought to bear
in order to ensure a wider range of drug therapies and expedited
availability of effective drugs.

 

 
 

 

Now I have the honor of handing the gavel to Dr. Frank Lilly
who will chair these hearings. As a New Yorker and chairman of
the Genetics Department at Albert Einstein College of Medicine,
Dr. Lilly is right at home. In addition to being a New Yorker,

Dr. Lilly’s expertise in retroviruses uniquely qualifies him to
chair this set of hearings.

 
 

 

TESTIMONY: PRESIDENTS AIDS COMMISSION
FEBRUARY 18, 1988

Frank J. Rauscher, Jr., Ph.D.
Senior Vice President for Research
Americon Concer Society
90 Park Avenue
New York, New York 10016

Mr. Chairman and distinguished members of the ponel. You and your task are
critically importont for this Nation and others as to prevention, detection, cure
and rehabilitation of AIDS.

My name is Dr. Frank J. Rauscher, Jr. and | presently serve as Senior Vice President
for Research, American Cancer Society. | believe you have my CV. My background,
in brief is as follows: | evolved through 10 years Academia, 18 years National Cancer
Institute, NIH and now 12 years American Cancer Society in the privote or voluntary
sector. During this time | have also advised and served on Boards of Industry, and
other Institutions - here and abroad.

| have been asked by one of the most innovative and productive scientists in this
country, Dr. Frank Lilly - a member of your commission to comment on the good
and not so good processes of “planning” - and eventual outcome, people benefit
wise.

! will do this briefly and then be most pleased to try to discuss any questions you
may have. | was trained as, and am a microbiologist - specifically as a virologist,
in the retroviruses that now have to do with the induction of AIDS and other diseases.

In 1964 | was appointed head of the Special Virus Leukemia Program (SVLP) which
! believe was the first major new program of the National Institutes of Health that
attempted to include planning as a major component of program implementation
and evaluation.

At that time, during the middle of a budget yeor, the National Concer Institute
(NCI) received a supplemental appropriation of $10 million with a mandate from
Congress to determine whether viruses were responsible for any human neoplosm
and to devise means for prevention.

While thot charge wes not fulfilled fully until Gallo, et. al discovered the
relationships of HTLV-1 and a form of adult leukemia in the early 1980's, the
technology coming out of that program provided the intellectual and technical
base for what is now being done with AIDS and HIV. Parenthetically, Dr. Lilly
was one of the first scientists supported by that program.

In terms of planning, a small number of NCI staff together with advice from outside
peer scientists, with approval and overview of the National Concer Advisory Council
attempted to do the following:

-Access history and state of the art in viral oncology.

-Determine what "critical path" might be followed to attain the objective quickly
and economically.

-Identify and solicit people and Institutions to do the work.

-Peer review, monitor and report.

-Updote a "rolling" 5 year plan.

These sub-objectives were accomplised but | believe a tactical misteke was made

 

 
 

 

-2-

in that the contract rather than the investigator initiated grant mechanism of funding
was chosen to support projects in this program. It conjured up the image of "big
brother" telling scientists what to do, how and when. Also, the program did not
have direct budgetary, staffing or reporting priority as the National Cancer Program
does now. Nonetheless in retrospect | believe it was a highly successful progrom.
This in terms of its potential and now realized impact on high incidence or traumatic
diseases that people fear most, Cancer and AIDS.

In 1970-71 President, Nixon, Congressman Rogers and Senator Kennedy committed
this Nation to a "Conquest of Cancer Program" with all needed funds and with
special bypass budget and reporting authority to the Executive and Congress. |
was appointed the first director of what came to be known as the National Cancer
Program (NCP-NCl). In my tenure through 1976 we committed about $3.5 billion
in the quest for improved prevention, cure and rehabilitation. | believe a relatively
smal! sum and very well used.

At about the same time (1970) over 1000 American and International Scientists
were convened to "plan" this attack. This followed the "Yarborough report" (Senator,
Texas) in which a pone! of experts judged that there was sufficient available
knowledge and technology, which if properly and widely applied, would result in
more meaningful benefit to people than then realized. | believe that was and is
true.

But in his "State of the Union" message and in comments mode later, the President
surmized that if this Notion could hit the moon, we ought to be able to "cure" cancer.
His conviction and goal were laudable but it burdened the program with overpromise
and overexpectoncy. We did not know then where the moon was nor how many
there were.

| urge you to plan but not to make that serious mistake.

| believe that planning is important, inexpensive and could be effective. It gets
people together to think ond the process is impressive to the Executive and Congress.
It is an invaluable tool in reporting to OMB and to the Authorization and
Appropriation Committees of Congress.

| believe firmly in the issues of Relevance, Priority, Need, Who and How as regards
to planning;

Relevance: The project (grant/procurement} must have a reasonable chance
of helping to attain the program goal.

Priority: Issues of merit and urgency. Money and talent are finite. No Nation
can do everything. Peer review is fallible but must choose the best bets now.
Reevaluate every 2 years.

Need: If its already being done well don't start a new program. Duplicate by
ol! means; different minds bring different and probably beneficial approaches
to a common goal. | do not think that overduplication (waste?) is a problem.

 

 

 
 

 

-j3-

Who: Get the best regarding track record and promise. Motivate, twist arms;
whatever.

How: For the most part review, fund and monitor investigator-initiated grants.
Secondly, (this can be tricky) solicit people ond institutions to do work (research,
reagent production, etc.) agreed upon as top priority by staff and outside peer

review.

Mr. Chairman this concludes my written statement. | thank you for this opportunity
and will be pleased to try to onswer questions ond to submit additional information

for the record.

 

 
 

 

THE FEDERAL ROLE IN AIDS RESEARCH: NIH

Anthony S. Fauci, M.D.

Director, National Institute of Allergy and Infectious Diseases
Coordinator of NIH AIDS Research

Summary of Testimony to the
President’s Commission on the Human Immunodeficiency Virus Epidemic
February 18, 1988

The National Institutes of Health (NIH) is a prominent partner in a
coordinated national effort to discover and evaluate promising approaches to
the understanding, treatment, and prevention of human immunodeficiency virus
(HIV) infection. Rapid progress has been made thus far, due in large part
to the extraordinary basic science research foundation developed over many
decades. The recognition of AIDS as a distinct entity, created the need for
intensive scientific study directed specifically at this new disease. The
current NIH budget reflects this surge in AIDS research, and at the present
time, virtually all of the NIH Institutes and Divisions are involved to a
greater or lesser degree in AIDS research. Several important mechanisms
have been established to provide coordination for NIH-wide AIDS research
activities, as well as with other Agencies of the Department of Health and
Human Services (DHHS) Agencies, Federal Agencies and International
Organizations involved in efforts to combat AIDS.

FUNDING

Over the roughly eight year period since the identification of AIDS,
federal funding for AIDS has grown dramatically to meet this enormous
challenge. The estimated total Public Health Service (PHS) AIDS budget for
Fiscal Year 1988 is roughly $951 million. Of the five Agencies that comprise
the PHS, the NIH AIDS budget represents by far, the largest percentage of
the PHS AIDS budget. During Fiscal Year 1988, NIH spending on AIDS research
is expected to reach almost $468 million. The budget has grown steeply since
the less than $3.5 million spending figure noted in 1982. At present, the
‘NIH AIDS budget represents approximately 7 percent of the total NIH budget
obligations. Not suprisingly, there is considerable range in the AIDS
budgets of the different NIH Institutes, based upon the nature and scope of
their AIDS activities. For example, The National Institutes of Allergy and
Infectious Disease (NIAID) is a major component in the NIH AIDS effort, with
an estimated budget of $223 million for Fiscal Year 1988 which represents
roughly 35% of the NIAID’s total budget obligations.

NIH AIDS funding can be broken down by funding mechanism. This year,
roughly 87% of the budget will support extramural programs, which includes
research project grants, research centers, research training, R & D
contracts and research management and support. The remaining proportion

 

 
 

 

(13%) will be used to support NIH intramural activities.

It may also be helpful to look at NIH AIDS funding by functional
categories, which correspond roughly to the areas of scientific endeavor to
be discussed below. Anticipated NIH AIDS funding by category for Fiscal Year
1988 include: (1) pathogenesis and clinical manifestations, $140 million
($99.6 million in FY 1987); (2) therapeutics research, $162.5 million ($122
million in FY 1987); (3) vaccine development and evaluation, almost $53.4
million ($26 million in FY 1987); (4) public health control measures, $17.5
million ($12.7 million in FY 1987); (5) patient care and public health
needs, $2.4 million ($232,000 in FY 1987); multidisciplinary AIDS research,
$4.7 million (2.6 million in FY 1987).

NIH AIDS RESEARCH EFFORTS

The NIH is responsible for funding and carrying out basic and clinical
research on the acquired immune deficiency syndrome (AIDS). The NIH AIDS
research efforts can be divided into five major scientific categories: 1)
epidemiology and natural history; 2) the etiologic agent; 3) pathogenesis;
4) the development and testing of anti-retroviral therapies and immunologic
reconstitution; and 5) vaccine development and evaluation. Significant
advances have been made in each of these categories, often at a pace
unprecedented in the history of biomedical science.

demiolo a atu sto

A substantial body of knowledge now exists about the epidemiology and
natural history of the disease. However, since the disease was only first
recognized in 1981, much remains to be learned about specific features of
HIV infection and the course of infection over the long term. While the
major responsibility for surveillance and epidemiologic studies rests with
the Centers for Disease Control (CDC), the NIH has many important efforts in
this area. The NIH has performed and continues to perform research
complimentary to that of the CDC in utilizing cohorts of prospectively
followed AIDS patients and healthy individuals practicing high risk behavior
as sources for basic and clinical research studies. NIH is conducting a
number of epidemiologic studies to examine the natural history of AIDS, the
biologic characteristics of the virus and the host response to HIV
infection. These studies include the prospective Multicenter AIDS Cohort
Study (MACS), begun in 1983, involving approximately 5,000 homosexual men in
four cities in the United States, as well as studies in Africa and the
Caribbean basin to define viral and host factors of HIV infection in those
regions. Other research investigations underway include the study of
heterosexual transmission in specific populations, and the study of women
and children at high risk for developing AIDS, including prostitutes,
pregnant women and children of women with HIV infection. Ongoing
surveillance studies of NIH employees working with AIDS patients or HIV
specimens confirm the low risk of transmission in these groups.

e Etiologic Age and e

 

 
 

 

In a remarkably short period following the recognition of AIDS, NIH-
supported research led to the discovery and identification of HIV as the
etiologic agent. Since that time, the virus has been isolated and cloned;
its genes have been identified, fully sequenced and thier functions
delineated. Insights into the pathogenesis of the disease (how the virus
destroys the body’s defenses) have occurred at a dramatic pace, although the
precise mechanisms remain to be determined. We can anticipate major
advances in this area in the near future. This research is ongoing at the
NIH and at many NIH-supported research sites.

Dru evelo t d Test

A major NIH effort has been directed toward the discovery and
development of anti-HIV drugs. The NIH is pursuing two basic approaches:
(1) the screening of large numbers of existing compounds for activity
against HIV, (2) targeted drug development using information gained about
unique properties and critical functions of the virus to design agents that
interfere with the life cycle or with structural components of the virus.

Rapid advances are being made in both these areas. New approaches to
screening, both in the test tube and in animals bearing human host cells
infected with HIV, are being actively explored. Azidothymidine (AZT), the
first and, at present, only drug licensed for use in AIDS was discovered
through in vitro screening. NIH recently initiated the National Cooperative
Drug Discovery Groups (NCDDGs), which represent an innovative, coordinated
effort to utilize top scientists and the capabilities of universities,
pharmaceutical companies, research institutes and other organizations, in
collaboration with the federal government, to discover and develop potential
new AIDS therapies through the stage of preclinical testing. Begun in 1986,
18 NCDDG’s are now established at research centers across the country.
Projects include: targeting of drugs to infected cells; studies of
physiochemical effects of drugs on cell structures; the development of
immunotherapies; studies of the antiviral effects of natural products and
synthetic compounds; studies of the biophysical properties of HIV and cell
proteins; the development of animal models for AIDS; and new biochemical
prescreening assays. In addition, NIH recently awarded six program project
grants to facilitate the organization of multidisciplinary research groups
to study the structural and biophysical properties of HIV and related
viruse. The NIH intramural program has also developed a targeted antiviral
effort utilizing a structural biology approach. The purpose of such efforts
is to develop drugs specifically targeted to virus based upon knowledge of
its structure.

The NIH has undertaken an enormous effort to evaluate potentially
effective therapies for persons with AIDS. An important early achievement
occured when NIH scientists, in collaboration with the Burroughs Wellcome
company, established that the drug AZT had anti-retroviral properties and is
effective in prolonging life in patients. AZT is currently being studied
alone and in combination with other agents in a variety of categories of HIV
infection. However, it is not a cure and is not without significant
toxicity. NIH is committed to the discovery of a less toxic and hopefully
curative agent for persons with HIV infection.

 

 

 
 

 

In order to rapidly and carefully investigate potential therapies, NIH
has established an extensive clinical trials network in which studies are
underway to determine the safety and efficacy of antiretroviral and
immunomodulatory treatment approaches in persons infected with HIV, as well
as specific therapies (including prophylaxis) for the opportunistic
infections and malignancies associated with HIV infection. Clinical trials
of promising agents/therapeutic approaches are being conducted both in the
intramural programs of the NIH and at academic institutions participating in
the AIDS Clinical Trial Group program (ACTG). Overall goals are: (1) to
ensure that high priority investigations are undertaken by quality
researchers using rigorous scientific standards and structured protocols;
(2) to develop new agents from preclinical studies to final FDA approval;
and (3) to provide timely information to guide physicians in selecting
appropriate treatment.

The ACTG program represents a major clinical initiative in the
evaluation of experimental treatments for HIV infected individuals. This
effort began several years ago with the establishment of 19 AIDS Treatment
and Evaluation Units (ATEUs) at medical centers throughout the country,
funded through NIH contracts to undertake clinical investigations of a
number of therapeutic agents.To complement that effort, the NIH then
developed the Clinical Studies Groups (CSGs), establishing 17 additional
clinical investigation sites located in areas of both high and low
endemicity for infection. These sites of clinical investigation (i.e. the
ATEU’s and CSG’s) have been coordinated into a unifying, cooperative group
structure, the ACTG program.

As of early February, 1988, accomplishments of the ACTG Program
include:
o 26 active protocols (4 completed with regard to patient
accession; 22 still accessing patients). Approximately 15

additional protocols are in final stages of review or approval.
o 18 agents under study:
Anti-HIV Therapies (alone or in combination, include

AZT, ddC, acyclovir, AL-721, Foscarnet, Desiclovir,
Interferon-alpha, Interferon-gamma, IL-2, Tumor
necrosis factor)

Biological Response Modifiers (Interferon-alpha,
Interferon-gamma, IL-2, Tumor necrosis factor)
° ° (Aerosol

pentamidine, DHPG, Trimetrexate, Amphotericin B,
Fluconazole, Trimethoprim-sulfamethoxazole)
e es fo -associated Ma ancies
(Radiotherapy, Doxirubicin)
o Soon to be tested (Ampligen, Ribavirin)
o To date, over 3,000 patients have been entered into studies.

Clinical trials of promising therapeutic agents are also ongoing in the
intramural programs at NIH. In addition, the NIH intramural program has
recently undertaken a very unique study of identical twin bone marrow
transplantation and syngeneic lymphocyte transfusion in HIV infection. Such
immunological reconstitution is still in the highly experimental stage.
However, this approach in combination with specific anti-retroviral therapy
provides the potential for a two-pronged attack aimed at suppressing virus

 

 
 

 

replication at the same time that damaged or destroyed immune function is
rebuilt.

Vaccine Development and Testing

The development of a vaccine against HIV infection has assumed a
prominent position in the strategies for prevention and control of AIDS, yet
remains one of the greatest challenges in combatting the epidemic. NIH has
mounted a major effort in the search for an AIDS vaccine based on a sound
scientific approach. The recently proposed NIH Plan for AIDS Vaccine
Development and Evaluation represents a comprehensive plan outlining
coordinated efforts and active participation by government, industry and
academia to foster the expedited development and testing of AIDS vaccines.
The plan includes basic research, preclinical development and clinical
testing.

Difficulties in the development of a safe and effective vaccine against
HIV include the complexity of the viral organism, the antigenic variations
of isolates, the lack of a clearcut delineation of protective immunity, and
the paucity of suitable animal models. Vaccine testing and evaluation is a
stepwise process that must be carefully designed to ensure that vaccines
are safe and elicit an immune response (immunogenicity). After safety and
immunogenicity are demonstrated in laboratory and animal tests, the vaccines
are clinically evaluated in humans.

In early 1988, the NIH will begin funding several National Cooperative
Vaccine Development Groups (NCVDGs) to foster collaboration among academia,
industry and governemnt and facilitate the development of an AIDS vaccine.
These multi-institutional, multi-disciplinary consortia will consist of
experienced investigators with a range of skills needed to explore the
various experimental approaches to AIDS vaccine development. Research
conducted by the NCVDGs will include basic studies, developmental studies,
scale-up and production, evaluation in laboratory animals and appropriate
clinical trials.

The NIH is also expanding its capacity to test candidate vaccines in
existing Vaccine Evaluation Units, funded by NIH and located at six medical
research centers nationwide. These have been supplemented to prepare for
AIDS vaccine testing and will serve as a national resource for the early
evaluation of candidate AIDS vaccines in clinical trials (phase I and II
testing). Future plans include further expansion and establishment of
additional Units to meet the anticipated needs for AIDS vaccine trials.

In October 1987, NIH began the first FDA approved Phase 1 clinical
trial of a candidate AIDS vaccine at the NIH Clinical Center. This study is
expected to involve 81 healthy volunteers. Companion trials have now been
approved to begin at the NIH funded Vaccine Evaluation Units, where a total
of 72 volunteers will be studied. These trials represent an important first
step among many necessary to determine whether this or another vaccine will
be safe and effective enough for general use. NIH is prepared to be flexible
and respond rapidly in the event that new and promising information on
potential vaccine candidates becomes available.

 

 
 

 

COORDINATION

In order to further strengthen AIDS research, NIH has instituted a
number of mechanisms to improve coordination, both throughout NIH and with
the broader research community. Areas of coordination include: (1) NIH
Interagency coordination, (2) Advisory groups, (3) Intramural scientific
coordination, (4) International coordination and (5) Industry/Academic
coordination.

I IDS Coordinatio

In order to ensure coordination of NIH-wide AIDS research activities,
several steps have been taken. The position of NIH AIDS Coordinator was
created in 1986. I am presently serving in that capacity, in addition to my
role as NIAID Director. An NIH AIDS Executive Committee has been established
to provide guidance and direction for NIH-wide scientific, planning and
resource allocation decision-making and facilitate effective coordination of
efforts. The membership of the committee, co-chaired by the Director of NIH
(Dr. Wyngaarden) and the NIH AIDS Coordinator (Dr. Fauci, Director of
NIAID), is comprised of the Directors of those Institutes which are
currently involved in AIDS research, as well as principal staff from the
Office of the Director, NIH. The Committee also links the activities of NIH
with other components of the Public Health Service (PHS) through the PHS
Executive Task Force on AIDS.

To further enhance NIH research activities, Secretary of Health and
Human Services, Dr. Otis Bowen recently established the AIDS Program
Advisory Committee, consisting of the Director of NIH as chair, and thirteen
members selected by the Secretary including nine individuals knowledgeable
in the basic science, biomedical and clinical care fields underlying
advances in AIDS research, as well as four representatives of the general
public. The purpose of the Committee, which is to have its initial meeting
at NIH on February 26, 1988, is to advise the NIH on all aspects of AIDS
research, identifying opportunities for further research and recommending
initiatives that should be undertaken to advance knowledge in the diagnosis,
prevention, and treatment of AIDS.

In addition, multiple other advisory groups exist to provide
coordination in areas relevant to NIH based or funded AIDS research. These
include: (1) Institute councils (NIAID and NCI have established specific
AIDS subcommittees), (2) Technical review committees, (3) Ad hoc advisory
groups on specific issues/topics, and (4) the Institute of Medicine.

NIH intramural research activities are coordinated with guidance from a
number of sources, importantly the NIH AIDS Executive, as well as such
groups and activities as the NIH Scientific Vaccine Development Committee,
Intramural Targeted Antiviral Development Program, DCT Decision Network
Committee, AIDS Clinical Drug Development Committee, and the NIH Bimonthly
AIDS Science Report.

The NIH has an active interest in close coordination with the

 

 
 

international health research community in the global effort to combat AIDS.
At the present time, the NIH has collaborative activities with the World
Health organization (WHO), the Pan American Health Organization (PAHO), the
Carribean Epidemiology Center (CAREC), International Collaboration in AIDS
Research (ICAR) and the Fogarty International Center.

The NIH has also stimulated a number of innovative programs to foster
industry and academic collaboration, in close coordination with the federal
government. A number of these projects were described earlier in the
discussion of drug and vaccine development and evaluation. Importantly they
include the National Cooperative Drug Discovery Groups (NCDDGs), the AIDS
Clinical Treatment Groups (ACTGs), The National Cooperative Vaccine
Development Groups (NCVDGs), the Vaccine Evaluation Units. and individual
collaborative agreements with industry.

Government -Wide AIDS Coordination

The NIH represents one of five agencies comprising the U.S. Public
Health Service, Department of Health and Human Services. The other PHS
Agencies include the Centers for Disease Control (CDC), Alcohol, Drug Abuse
and Mental Health Administration (ADAMHA), the Food and Drug Administration
(FDA), and the Health Resources and Services Administration (HRSA). The
Public Health service has placed the fight against AIDS at the very top ot
its public health priority agenda. Coordination of AIDS activities within
the PHS and throughout the federal governement is a major concern. I will
now briefly describe some of the mechanisms in place to strengthen
coordination at this level.

The PHS Executive Task Force on AIDS was established in May 1984, and
serves as a major coordinating and focal point for all PHS and DHHS AIDS
activities. The mission of the group is to advise the Assistant Secretary
for Health on AIDS related issues, to coordinate AIDS activities among PHS
Agencies, provide a forum for achieving concensus on AIDS issues, develop
operating strategies for PHS AIDS activities and provide a conduit for AIDS
information sharing among members. The Task Force is chaired by the
Assiastant Secretary for Health, Dr. Robert E. Windom and co-chaired by the
PHS AIDS Coordinator, Dr, Peter Fischinger. Members of the Task Force
include Agency Heads and represenatatives of the PHS Agencies and the
Office of the Assistant Secreatry for Health (OASH).

To facilitate improved communication and collaboration throughout the
Federal Government, the Public Health Service established a Federal
Coordinating Committee on AIDS Information, Education and Risk Reduction.
First convened in December 1986, the Committee is composed of seven Federal
Departments (USDA, DOD, DOED, HUD, DOJ, DOL and DOS), six independent
agencies (Action, AID, EPA, OPM, USIA, and VA), and three offices within the
Executive Office of the President (The Domestic Policy Council, the Office
of Management and Budget, and the Office of Science and Technology Policy).
The Departments and Agencies all have constituencies, networks, and issues
that make them crucial in coordination of government-wide AIDS efforts. From
a broad perspective, the committee is responsible for identifying
government-wide issues, information/research/resource needs and gaps, and
appropriate goals in the effort to combat AIDS.

 

 
 

 

Statement

of

Vic Basile, Executive Director
Human Rights Campaign Fund
Before The

President’s Commission On The HIV Epidemic

February 18, 1988

New York City, New York

1012 14th Street, N.W. Suite 607 Washington, D.C. 20005 202/628-4160

 

 

 
 

 

HRCF Testimony, 02/17/88: page 1

Mr. Chairman and members of the Commission:

My name is Vic Basile and I am the Executive Director of the
Human Rights Campaign Fund, which lobbies in Washington on behalf
of the nation’s gay and lesbian community. I want to thank the
Commission for this opportunity to present our views on the
federal AIDS research effort, and some suggestions for improving
the management of that effort.

There must be an urgent response to this crisis from the
federal government, and from every sector of society. The
importance of prevention is obvious, given the present lack of
effective treatment for HIV infection. Tragically, prevention
has become very controversial as common-sense measures have come
under ideological attack from the uninformed and the uncaring.

The necessity for medical research should be equally
obvious, as experts predict that 1 1/2 million or more Americans
may already be infected and more are being infected each day.
Research in the natural history of the infection yields
increasingly frightening results, with many knowledgeable people
now predicting that most, if not all, of those infected will
become seriously ill and die prematurely unless effective
treatments are developed.

In the next two days you will hear from other witnesses who
will inform you of the widespread use of alternative therapies
for AIDS, ARC, and HIV infection. I have here models of two
medicine cabinets. One is full of bottles, to represent the

myriad drugs under investigation as therapies in HIV infection,

 

 
 

 

HRCF Testimony, 02/17/88: page 2
which have not been licensed by the FDA. Many of them are in
widespread use in the community.

In the other is one bottle, representing AZT, the one drug
licensed by the FDA for treatment of HIV infection. This single
drug still represents the great majority of the AIDS clinical
trial work being performed by the NIH. The space between, you
could say, represents the tragic chasm between hope and reality
for 11/2 million Americans infected with HIV.

I speak as one who, like most gay men and lesbians, counted
as friends many of the 30,000 Americans who have already died
from AIDS. I have attended funerals just in the last month for
two friends: Jim Kamel and Dan Bradley, former president of the
Legal Services Corporation. It was painful to lose them, as it
was painful to lose many friends before them--more now than I
care to count. But that pain is magnified many times as I look
around me at so many other friends who are living and struggling
each day with AIDS, ARC, and HIV infection. If there is not
rapid progress in medical treatment, we will lose them and so
many others.

To add urgency to this need, there are many promising signs
that an intensive effort will yield solutions in the near future.
Nobel laureate Dr. David Baltimore, speaking to the National
Academy of Sciences in September, said that developing therapies
for HIV infection is a relatively simple scientific problem--
compared, say, to cancer. He stated that the “research menu,"

while enormous, "is well defined and lends itself to directed

 

 
 

 

HRCF Testimony, 02/17/88: page 3

management." Similarly, Dr. William Haseltine of Harvard Medical
School said in December that he is "convinced we can prevent and
treat this disease. It’s a question of applying, in a systematic
way, the knowledge and the opportunities that we have."

Dr. Baltimore’s remarks are included with our written
statement. I will submit to the Commission copies of our
compendium, MEDPAC, which is a compilation of both scientific and
lay reporting on AIDS research. This compilation reveals that
progress in AIDS research has been rapid and--most importantly--
that there are numerous promising candidates on the horizon to
treat HIV infection or its most serious consequences. The only
issue is how quickly can promising candidates be transformed into
therapies available to infected people and. their physicians?

In his remarks to the NAS, Dr. Baltimore went on to say
{emphasis added]:

We all know that science and testing take time. ...

Therefore, our only response to a concerned public is

that we are doing everyting we can as fast as we can.

To make that argument, we ought to be able to say that
we are working at crash program speed with an

integrated and comprehensive plan. Can we say that

today? ‘

I’m afraid we can’t. Granted, we have made progress; a few
years ago most of the nation felt it could ignore this disease as
somebody else’s problem, ‘and federal funding of research efforts

was woefully inadequate. Today serious money is at last being

 

 
 

HRCF Testimony, 02/17/88: page 4

devoted to AIDS, and the entire federal establishment appears to
recognize the need for increasing the effort. What is still
missing, though, is a sense of urgency that permeates the federal
establishment--beyond the laboratories where AIDS research is
actually conducted--a recognition that we are in the midst of a
crisis.

We believe that the political establishment, and this
Commission, can be most useful in improving the management of
federal research efforts, so that increased resources can be
translated as quickly and efficiently as possible into greater
scientific effort.

A model for such efforts is the Accelerated Solicitation-to-
Award Process, or ASAP, plan that has been prepared recently by
NIH. This plan provides for the review of grant applications
within 6 months of submission. It requires new "fast-track"
procedures whereby some steps in the process are taken
concurrently rather than serially, and other steps are eliminated
or abbreviated. This requires additional resources in some
areas--particularly certain support staff--and it also requires
the cooperation of other government agencies and the private
sector.

This type of plan needs to be developed on a coordinated
basis in all the federal agencies involved in any way with AIDS
research. As a first step, the Executive Branch should establish
an Interagency Task Force to audit all federal agencies involved

in the research effort (NIH, FDA, OMB, OPM, GSA, etc.), identify

 

 
 

 

HRCF Testimony, 02/17/88: page 5

impediments to the efficient and effective expenditure of funds
previously appropriated, and document future needs for
consideration by the Executive Branch and the Congress.

There is also an immediate need for greater resources,
particularly space and personnel. Medical researchers are
demanding more nurses, technicians, and analysts in order to
proceed with desired scientific research. Because of outmoded
pay scales, senior NIH scientists are leaving the institution.
There is a shortage of adequate facilities for medical research:
laboratories, extramural research centers, and office space. The
Commission should recommend several steps to correct these
problems.

Federal personnel policies must be revised to attract and
retain senior scientists, nurses, technicians, analysts and other
scientific and medical professionals in numbers necessary to meet
present and projected needs. Institutions involved in AIDS
research should be exempt from personnel ceilings. It is not
adequate to exempt AIDS research from personnel ceilings if the
net effect is to require other functions to absorb cuts without
corresponding diminution in responsibilities.

The Executive Branch should conduct an inventory of
facilities and develop a plan to meet those needs, including
proper and suitably located laboratory space, biocontainment
facilities, office space, hospital beds, and out-patient space as
well as instruments and equipment.

The largest gap in the national AIDS effort may be the lack

 

 
 

 

HRCF Testimony, 02/17/88: page 6

of collaboration with private industry. Several mechanisms for
closing that gap can be found in the Stevenson-Wydler Federal
Technology Transfer Act, which can facilitate consortium
arrangements between private industry and federal research
institutions. The NIH and its member institutes have just begun
to use this law to develop and take advantage cooperative
agreements with industry, and has not yet promulgated
implementing regulations. All affected agencies should explore
the potential use of this law in AIDS research.

The federal research effort must learn from community-based
networks for alternative AIDS therapy. The planning of federal
drug-development research must include the active participation
of knowledgeable representatives of HIV-infected people and their
health-care providers. They can provide essential information
about the medical needs of the affected people, the impact of
trial design on them, and measures they are taking that will make
different trial designs more or less useful. The same mechanisms
can then be used to disseminate the results of research rapidly
to then.

We cannot ignore the international dimensions of this
pandemic. The U.S. must assume a more prominent role
internationally in marshalling our enormous scientific resources
to assist in the global fight against AIDS. Through vigorous
participation in the efforts of the World Health Organization,
the U.S. can work to ensure that the research and development of

new drugs, and in the future a vaccine, is carried out with as

 

 
 

HRCF_ Testimony, 02/17/88: page 7

much cooperation as possible. Other populations in the world are
experiencing AIDS as an epidemic that is different from and
perhaps represents the future of our own. Our scientific
community needs to learn from these various medical experiences
in order to be more full certain of the results discovered in the
United States.

Legislation responsive to the needs of effective research
management should be passed by the Congress or, where possible,
implemented by Executive Order. Congress has taken three small
but significant steps to expedite research objectives. In the FY
1988 Continuing Resolution, Congress directed NIH to process
grant and contract applications within six months of submission,
as the NIH has prepared to do in its ASAP plan; it required OPM
and GSA to respond to resource requests for AIDS research within
21 days; and it directed the expansion of clinical trials for
promising, experimental drugs.

Legislation is currently pending in both houses of Congress
that addresses these concerns in a comprehensive fashion. These
bills--S. 1220 and H.R. 3825--would require the expeditious
approval of research contacts, prompt responses to priority
requests for allocations of funds, services and personnel,
expansion of clinical trials, greater collaboration by government
and industry, increased international efforts, and bringing on-
line needed research facilities. H.R. 3825 would also create
mechanisms to encourage community-based research initiatives, and

to incorporate their successes into the federal structure. These

 

 
 

 

HRCF Testimony, 02/17/88: page 8

bills should be passed and signed into law as soon as possible.

It is important to note, however, that all of these measures
can be implemented through administrative actions. We do not
need to wait for Congress. We do not need to wait for a
resolution of the controvery around testing, discrimination, or
education.

All that is lacking is the will to act, and to act now. The
Human Rights Campaign Fund urges this Commission to call on the
President to implement the measures we have described. Such
action by our highest public servant would command instant
attention and support. This Commission can present this critical
opportunity to the President. We can together embark on this
course today.

Thank you.

 

 
 

 

AIDS Products In Development

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Anti-virals
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
AL-721 Ethigen ARC, PGL IND approved
(AL-721) (Los Angeles, CA) Phase II
Betaseron Triton Biosciences AIDS, Kaposi’s sarcoma, ARC IND approved
(unterferon beta) (Shell Oil) Phase I/II
(Alameda, CA)
Cytovene Syntex CMV NDA Pending
(gancclowr) (Palo Alto, CA) (Orphan Drug)
DDC Hoffmann-La Roche AIDS, ARC IND approved
(dudeorycytudine) (Nutley, NJ) Phase [/II
(dextran sulfate; Ueno Fine Chem. Industry AIDS, ARC IND approved
UA001) (Osaka, Japan) Phase I
Foscarnet Astra Clinical Research HIV infection, CMV retinitis IND approved
(trisodium (Hoplanton, MA) Phase I/II
phosphonoformate) :
HPA-23 Rhone-Poulenc Sante HIV infection IND approved
(Monmouth Junction, NJ) Phase I
Ornidy! Merrell Dow PCP NDA pending
(eflornithine) (Cincinnati, OH) (Orphan Drug)
Peptide T Peninsula Labs AIDS IND approved
(octapeptide sequence} (Belmont, CA) Phase I
Reticulose Advanced Viral Research AIDS, ARC IND submitted
(nucleophosphoprotem) (Miami, FL)
Retrovir Burroughs Wellcome AIDS, adv. ARC NDA approved
(zidovudine; AZT) (Rsch. Tnangle Park, NC)
pediatric AIDS, Kaposi’s sarcoma, IND approved
asymptomatic HIV infection, less severe Phase I/II
HIV, neurological involvement, in com-
bination w/other therapies
Rifabutin Adria Labs ARC IND approved
(ansamycin LM 427) (Dublin, OH) Phase II
(trimetrexate) Warner-Lambert PCP IND approved
(Morris Plains, NJ) Phase ITI
Virazole Viratek/ICN AIDS, Kaposi’s sarcoma, ARC IND approved
(nibamrin) (Costa Mesa, CA) Phase I/II
Wellferon Burroughs Wellcome Kaposi's sarcoma, HIV, in combination IND approved
(alpha interferon) (Rsch. Triangle Park, NC) w/Retrovir Phase I
Zovirax Burroughs Wellcome AIDS, ARC, in combination w/Retrovir IND approved
(acyclonr) (Rsch. Triangle Park, NC) Phase I
Fmmun>-modulators
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
ABPP Upjohn Advanced AIDS, Kaposi’s sarcoma IND approved
(orommmane) (Kalamazoo, MI) Phase I/II
AS-101 Scientific Testing AIDS IND approved
(National Patent Develop-
ment, Bar Ian University,
Israel)
(New York, NY)
Ampligen DuPont ARC, PGL IND approved
(mismatched RNA) (Wilmington, DE) Phase IIIT
HEM Research
(Rockville, MD)
(antr-human alpha _ Advanced Biotherapy AIDS, ARC IND approved
anterferon antibody) Concepts Phase I
(Rockville MD)
Carrisyn Carmngton Labs ARC IND submitted
(acemannan) (Irving, TX)
Colony Stimulating Sandoz AIDS, Kaposi’s sareoma, ARC, HIV IND approved
Factor (East Hanover, NJ) Phase I
(GM-CSF) Genetics Institute
(Cambridge, MA)

 

Provided as a Public Service by the Pharmaceutical Manufacturers Association

 

 
 

 

 

Inununo-modulators

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
CL246, 738 American Cyanamid AIDS IND approved
(CL246, 738) (Pear! River, NY) Phase I/II
(gamma interferon) Genentech ARC, in combination w/TNF (tumor IND approved
(S. San Francisco, CA) necrosis factor) clinical tnals
IMREG-1 Imreg AIDS, Kaposi’s sarcoma, ARC, PGL IND approved
(New Orleans, LA) Phase IT]
IMREG-2 Imreg AIDS, Kaposi’s sarcoma, ARC, PGL IND approved
(New Orleans, LA) Phase II
Imuthiol Merieux Institute AIDS, ARC ‘IND approved
(diethyl dithro (Miami, FL) Phase I/II
carbamate)
IL-2 Cetus _ AIDS, Kaposi’s sarcoma IND approved
(interleukin-2) (Emeryville, CA) Phase II
IL-2 Hoffmann-La Roche Kaposi’s sarcoma IND approved
(unterleukin-2) (Nutley, NJ) Phase III
Immunex
(Seattle, WA)
INTRON-A Schering-Plough Kaposi's sarcoma NDA filed
(interferon alpha) (Madison, NJ)
Isoprinosine Newport Pharmaceuticals ARC, PGL, HIV seropositive IND approved
(inosine pranobex) (Newport Beach, CA) asymptomatic patients Phase ITI
(methonine TNI Pharmaceuticals AIDS, ARC Investigator’s IND approved
enkephalin) (Chicago, IL) Phase I/II
MTRPE Ciba-Geigy Kaposi’s sarcoma IND approved
(muramyl-tripeptide) (Summit, NJ) Phase I
Thymopentin Ortho Pharmaceuticals HIV infection IND approved
(TR5) (Raritan, NJ) Phase I/II
(thymic compound)
Roferon-A Hoffmann-LaRoche Kaposi's sarcoma NDA filed
(interferon alpha) (Nutley, NJ)
(recombinant Ortho Pharmaceuticals severe anemia assoc w/AIDS and AZT IND approved
erythropoietin) (Raritan, NJ) therapy Phase II
Trexan DuPont AIDS, ARC early Phase I]
(naltrexone) (Wilmington, DE)
TNF Genentech ARC, in combination w/gamma IND approved
(tumor necrosis (S. San Francisco, CA) interferon clinical trials

factor)

 

 

 
 

--DRAFT--

TESTIMONY OF WILLIAM A. HASELTINE, PH.D.

TO THE PRESIDENT'S COMMISSION ON AIDS

FEBRUARY 18, 1988

 

 
 

 

GOOD AFDERNOON.

THE TOPIC THAT I SHALL ADDRESS TODAY IS THE PROSPECT FOR THE MEDICAL

CONTROL OF THE AIDS EPIDEMIC. THE THREE TOOLS MEDICAL SCIENCE CAN PROVIDE IN

THE BATTLE TO CONTROL THE AIDS EPIDEMIC ARE:

DIAGNOSIS - THE ABILITY TO DETECT THOSE INFECTED WITH THE AIDS VIRUS.

TREATMENT - THE ABILITY TO PROVIDE MEDICAL CARE FOR THOSE INFECTED.

PROPHYLAXIS - THE ABILITY TO PREVENT THE INFECTION UPON EXPOSURE TO THE AIDS

VIRUS.

THE PROSPECTS FOR DEVELOPMENT OF THESE THREE FUNDAMENTAL TOOLS FOR CONTROL

OF THE AIDS EPIDEMIC ARE BRIGHT. THEY ARE WITHIN OUR CURRENT TECHNICAL ABILITY

- NOT NECESSARILY IN THE PRECISE FORM WE MAY WISH, BUT AVAILABLE NONETHELESS.

 

 
 

 

DIAGNOSIS

THE DISCOVERY OF THE ETIOLOGIC AGENT OF AIDS, A RETROVIRUS KNOWN NOW AS
HIV, BROUGHT WITH IT THE ABILITY TO DIAGNOSE MOST INFECTIONS. DIAGNOSIS CAN BE
RAPID AND ACCURATE. THE INTRODUCTION OF NEW, SIMPLE, RAPID AND EVEN MORE
ACCURATE TESTS ARE ONLY MONTHS AWAY. SOON IT SHOULD BE POSSIBLE TO MAKE A
PRELIMINARY DIAGNOSIS OF INFECTION WITHIN MINUTES AND A DEFINITIVE DIAGNOSIS OF
INFECTION WITHIN HOURS.

ONE OF THE MOST SURPRISING AND UNNECESSARY ASPECTS OF OUR APPRECIATION OF
THE SCOPE OF THE AIDS EPIDEMIC IN THE UNITED STATES HAS BEEN OF ABSENCE OF
SYSTEMATIC-CROSS-SECTIONAL SURVEY DATA OF THE POPULATION. FOR THE PAST FOUR
YEARS, IT HAS BEEN POSSIBLE TO GAUGE ACCURATELY THE EXTENT OF AIDS VIRUS INFEC-
TION IN THE POPULATION VIA ANONYMOUS CROSS-SECTIONAL TESTING. WITHOUT SUCH
INFORMATION, THE EXTENT OF THE PROBLEM IN DIFFERENT POPULATIONS IS CONJECTURE,
THE RATE OF SPREAD OF THE DISEASE WITHIN AND BETWEEN POPULATION GROUPS IS
UNKNOWN, AND THE EFFECT OF EDUCATION CONTROL PROGRAMS IS UNMEASURED. WE HAVE
BEEN, AND TO A LARGE EXTENT STILL ARE, FLYING BLIND WITH RESPECT TO OUR KNOWL-
EDGE OF THE KrAdudkys OF THE AIDS EPIDEMIC. WE SHOULD BROOK NO DELAY NOR ACCEPT

DY NemMic>

ANY EXCUSE FOR THIS DEPLORABLE LACK OF KNOWLEDGE .

 

 
 

 

THERAPY
TREATMENT OF THOSE INFECTED WITH THE AIDS VIRUS CAN BE DIVIDED INTO THREE

CATEGORIES.

- TREATMENT OF THOSE WITH ADVANCED ILLNESS, THOSE WITH SEVERE DAMAGE OF
é f
THE rms OR CENTRAL NERVOUS SYSTEM FUNCTION.
CERMT@AL
- TREATMENT OF THOSE WITH DETECTABLE, BUT MILDER IMMUNE OR CONTROL
NERVOUS SYSTEM ABNORMALITIES.

- TREATMENT OF THE INFECTED (HIV-SEROPOSITIVE) PEOPLE WHO HAVE NO

SERIOUS SYMPTOMS OF INFECTION.

TOWARD CURATIVE THERAPY

UNTIL RECENTLY ATTENTION HAS BEEN FOCUSED UPON TREATMENT OF THOSE WITH
co
SERIOUS DISEASE. PROGRESS IN EXTENDING THE LIFE EXPEWTANCY OF SOME PEOPLE HAS
BEEN MADE. SUCH PROGRESS IS ALL THE MORE REMARKABLE AS IT IS LIKELY THAT THE
Porson
PEVEBOXOMITH SERIOUS DISEASE WILL ULTIMATELY PROVE TO BE THE MOST DIFFICULT TO

TREAT. ATTENTION IS NOW TURNING TOWARDS TREATMENT OF THE INFECTED BUT

ASYMPTOMATIC PERSON.

 

 
 

 

OVER THE PAST SEVERAL YEARS WE HAVE DEVELOPED A MUCH BETTER UNDERSTANDING
OF THE NATURAL COURSE OF HIV INFECTION. THE GREAT MAJORITY OF THOSE INFECTED
ARE VERY LIKELY TO DEVELOP SERIOUS, AIDS VIRUS-RELATED, LIFE-THREATENING DISEASE

WITH TEN YEARS OF INFECTION. THE GOAL OF TREATMENT OF THE ASYMPTOMATIC HIV

INFECTED PERSON IS TO RETARD, AND HOPEFULLY TO PREVENT, THE DEVELOPMENT OF

— ae,

 

SERIOUS DISEASE. IT MAY NEVER PROVE POSSIBLE TO FULLY REVERSE THE DAMAGE DONE
T@om

BY THE AIDS VIRUS, BUT IT MAY VERY WELL PROVE POSSIBLE TO PREVENT THE DAMAGE FOR
EVER OCCURRING. I LOOK FORWARD TO THE DAY WHEN DIAGNOSIS OF INFECTION OF HIV IS
SIMILAR TO A DIAGNOSIS OF DIABETES ~ WITH PROPER AND CONTINUAL MEDICAL CARE,
THOSE INFECTED CAN LOOK FORWARD TO A NORMAL, FULL TERM LIFE.

I BELIEVE SUCH TREATMENTS ARE WITHIN OUR ABILITY TO ACHIEVE GIVEN OUR
CURRENT BIOMEDICAL SKILLS. SYSTEMATIC, INTENSE, CO-ORDINATED APPLICATION OF

EXISTING SCIENTIFIC AND MEDICAL RESOURCES IS VERY LIKELY TO BE UP TO THE TASK.

GIVEN APPROPRIATE RESOURCES AND COMMITMENT OF GOVERNMENT, INDUSTRY AND ACADEMIC

INSTITUTIONS THE PROBLEM CAN BE SOLVED.
I BASE THIS oprrursuJoy" CLOSE OBSERVATION OF THE DISEASE ORGANISMS ITSELF.
MY SPECIALTY IS MOLECULAR BIOLOGY - THE TAKING APART OF THE AIDS VIRUS

BIT-BY-BIT - AND ITS REASSEMBLY - TO SEE HOW THE VIRUS WORKS IN DETAIL. THE

 

 
 

 

MORE WE STUDY THE VIRUS, THE MORE WE ARE CONVINCED THAT IT IS VULNERABLE TO

MANY DIFFERENT KINDS OF ATTACK. BOTH CHEMICALS AND SUBSTANCES KNOWN AS BIOLOGI-
s

CAL RESPONSE MODIFIERS - INTERFERONS, GROWTH FACTOR, INTERLEUKINS AND CYTOKINES -°

HAVE BEEN SHOWN TO INTERFERE WITH VIRUS GROWTH. AT LATEST COUNT, THERE WERE

MORE THAN FOURTEEN DIFFERENT POINTS OF ATTACK. ADDITIONALLY, THERE ARE MULTIPLE

WAYS TO MOUNT EACH ATTACK.

ENLIGHTENED SCREENING

HOW CAN NEW DRUGS THAT ACT AGAINST THE AIDS VIRUS BE FOUND? SUCH DRUGS ARE
DISCOVERED EITHER BY A PROCESS I SHALL CALL “ENLIGHTENED SCREENING" OR BY
RATIONAL DRUG DESIGN. SCREENING, OF COURSE, MEANS SIFTING THROUGH MANY CHEMI-
CALS LOOKING FOR ONE THAT STOPS THE AIDS VIRUS. THANKS TO ADVANCES IN
BIOTECHNOLOGY, THIS PROCESS CAN BE VASTLY SPEEDED UP. SCREENING PROGRAMS FOR
EACH COMPONENT PART OF THE AIDS VIRUS ARE BEING DEVELOPED. IT IS EXPECTED THAT
BY THE END OF THIS YEAR TWENTY THOUSAND COMPOUNDS WILL BE EXAMINED. NEXT YEAR
IT IS EXPECTED THAT MORE THAN FORTY THOUSAND NEW COMPOUNDS WILL BE EXAMINED.

THE DISCOVERY OF AN ACTIVE COMPOUND MARKS JUST THE BEGINNING OF THE DRUG

DISCOVERY PROCESS. GIVEN ONE ACTIVE COMPOUND, A TEAM OF CHEMISTS CAN, IN A

 

 

 
 

 

SINGLE YEAR , MAKE HUNDREDS AND SOMETIMES EVEN THOUSANDS OF SIMILAR CHEMICALS -
EACH SLIGHTLY DIFFERENT. FROM SUCH A COLLECTION OF COMPOUNDS MAY EMERGE ONE
THAT HAS PROPERTIES BETTER THAN THE ORIGINAL THE PROCESS OF TAKING A
LEAD COMPOUND TO DEVELOPMENT AS A DRUG IS A FAMILIAR ONE FOR ALL LARGE PHARMA-

CEUTICAL FIRMS.

RATIONAL DESIGN

THE TOOLS OF MODERN MOLECULAR BIOLOGY, BIOCHEMISTRY AND MEDICAL DISCOVERY
HAVE OPENED NEW HORIZONS FOR DRUG DEVELOPMENT. WE ARE ENTERING THE ERA OF
RATIONAL DRUG DESIGN. MOLECULAR BIOLOGY AND BIOCHEMISTRY CAN PROVIDE VIRTUALLY
UNLIMITED QUANTITIES OF PROTEINS OF THE AIDS VIRUS. THE POSITION OF EACH ATOM
IN SPACE RELATIVE TO ONE ANOTHER CAN BE DETERMINED BY X-RAY CRYSTALLOGRAPHY OR
2-NUCLEAR MAGNETIC RESONANCE. THE INTERACTION OF EACH MOLECULE WITH KNOWN DRUGS
CAN BE STUDIED. PREDICTIONS FOR NEW DRUGS CAN BE MADE. SUCH NEW DRUGS CAN BE
CHEMICALLY SYNTHESIZED AND TESTED. THIS IS NO rrerane »
ALREADY THREE COMPONENTS OF THE AIDS VIRUS HAVE BEEN PRODUCED IN ABUNDANCE AND

CRYSTALLIZED. THE COMPLETE STRUCTURE OF THESE PROTEINS SHOULD BE AVAILABLE BY

 

 
 

 

a

7 Wy 19 be
THE END OF Ja YEAR OR THE MIDDLE OF NEXT. THE STRUCTURE OF OTHERS WILL FOLLOW
hr

SHORTLY.

‘WITH MODERN TECHNOLOGY, THE AVAILABILITY OF NEW ANTI-VIRAL COMPOUNDS IS

one? BY
LIMITED RESOURCES, AND THE INTEREST AND IMAGINATION OF THE SCIENTIFIC COMMUNITY.
f'

WITHIN A YEAR OR TWO THE PROBLEM OF DRUG SELECTION WILL BE A FORMIDABLE ONE AS

THERE WILL BE AN ABUNDANCE OF CANDIDATES.

Woe AO
HAVE BEEN WITNESS TO THE BIRTH OF A LARGE, ACTIVE, IMAGINATIVE

qemameneete es,

 

CO-ORDINATED DRUG DISCOVERY PROGRAM. OVER THE PAST TWO YEARS, VIA A VARIETY OF

 

FUNDING MECHANISM, THE NATIONAL INSTITUTES OF HEALTH HAVE FORGED AN ALLIANCE

 

 

BETWEEN INDUSTRIAL, ACADEMIC AND GOVERNMENT LABORATORIES TO FOSTER PRE-CLINICAL
DRUG DEVELOPMENT. THE PROGRAM IS A MODEL OF ITS KIND AND HAS ALREADY ENGAGED
SOME OF THE BEST SCIENTISTS OF OUR TIME. THE PROGRAM IS NOW EXPANDING. IN MY

OPINION SHOULD EXPAND STILL FURTHER OVER THE NEXT FEW YEARS.

THE PACE OF DEVELOPMENT OF NEW THERAPIES
IT IS THE PACE OF THE DISEASE ITSELF RATHER THAN THE PACE OF DRUG DISCOVERY
THAT WILL ULTIMATELY DETERMINE HOW RAPIDLY CURATIVE THERAPY CAN BE DEVELOPED.

THE TIME BETWEEN INFECTION AND FIRST SERIOUS SYMPTOM IS TYPICALLY BETWEEN TWO TO

 

 
 

 

FIVE YEARS OR MORE. THIS uf PERIOD MEANS THAT EVALUATION OF THE EFFICACY OF
TREATMENTS DESIGNED TO EXTEND THE LATENT PERIOD WILL REQUIRE AT LEAST TWO YEARS.

THE ONLY MEANS OF SHORTENING THIS PERIOD IS TO PLAN TRIALS USING THOUSANDS OF

PEOPLE.

THE SHAPE OF THINGS TO COME.
IT IS LIKELY THAT THE BEST TREATMENT WILL INVOLVE COMBINATIONS OF TWO OR
MORE DRUGS. COMBINATIONS OF DRUGS | CAN REDUCE TOXIC SIDE EFFECTS.
DRUGS CAN ACT IN CONCERT AGAINST THE VIRUS, MULTIPLYING THEIR EFFICACY
WITHOUT EFFECTING NORMAL CELL FUNCTIONS. COMBINATIONS OF
DRUGS CAN HELP PREVENT DEVELOPMENT OF DRUG RESISTANT STRAINS OF THE AIDS VIRUS.

COMBINATIONS OF DRUGS MAY ALSO PREVENT DISEASE PROGRESSION AS WELL AS TRANSMIS-

SION FROM AN INFECTED TO AN UNINFECTED PERSON.

PROPHYLAXIS

TO THINK OF PREVENTION IS TO THINK OF A VACCINE - A MEDICATION THAT ENABLES

THE IMMUNE SYSTEM TO PROTECT US FROM DISEASE. VACCINES ARE IDEAL AS A PUBLIC

 

 
 

 

HEALTH MEASURE. ENTIRE POPULATIONS CAN BE PROTECTED BY A ONCE IN A LIFETIME -
OR PERHAPS ONCE A YEAR AND MEDICAL INTERVENTION.

WHAT ARE THE PROSPECTS FOR AN AIDS VACCINE?

UNFORTUNATELY NO ONE CAN PREDICT WITH CERTAINTY THAT AN AIDS VACCINE CAN
EVER BE MADE. THAT IS NOT TO SAY IT IS IMPOSSIBLE TO MAKE SUCH A VACCINE, ONLY
THAT WE ARE NOT CERTAIN OF SUCCESS. I REMAIN CAUTIOUSLY OPTIMISTIC THAT GIVEN A
SUFFICIENT EFFORT BY VIROLOGISTS AND IMMUNOLOGISTS, A VACCINE CAN BE DEVELOPED.
INDEED, I AM VERY ACTIVELY ENGAGED IN VACCINE DEVELOPMENT. HOWEVER, IT IS
CERTAIN THAT WE FACE SIGNIFICANT PROBLEMS.

THE EXTENT OF THE PROBLEMS FOR AIDS VACCINE DEVELOPMENT WAS HIGHLIGHTED BY
THE FAILURE OF INITIAL VACCINE TRIALS IN ANIMALS. CHIMPANZEES IMMUNIZED WITH
VACCINE CANDIDATES WERE NOT PROTECTED FROM AIDS VIRUS INFECTION. MONKEYS

to PRE
TREATED WITH A VACCINE CANDIDATE FOR THE SIMIAN AIDS VIRUS WAS Be NOT PROTECT-
ED. FAILURE OF THE FIRST VACCINE TRIALS DOES NOT MEAN HOPE IS LOST. HOWEVER,
IT DOES MEAN THAT THE ROAD AHEAD MAY BE LONG AND DIFFICULT.

WE HAVE NOW GAINED ENOUGH INSIGHT INTO THE WORKING OF THE AIDS VIRUS TO

PERMIT INSIGHT INTO WHY VACCINATION MAY BE DIFFICULT.

 

 
 

 

such

THE FUNDAMENTAL REASONS FOR THE DIFFICULTY IS THAT THE AIDS
PG TO Hee
nprefvares HBS EVOLVED TO CO-HABIT WITH THE HUMAN BODY IN SPITE OF THE IMMUNE RE-
IK
SPONSE. IT IS ONE OF A NUMBER OF VIRAL PARASITES THAT ESTABLISH LONG TERM
RESIDENCE.

SPECIFIC MECHANISMS FOR EVASION OF THE IMMUNE RESPONSE BY THE AIDS VIRUS

ARE OF TWO TYPES.

- THE STRUCTURE OF THE SURFACE OF THE VIRUS IS DESIGNED TO EVADE THE
IMMUNE RESPONSE.

7 THE LIFE CYCLE OF THE VIRUS PERMITS IT TO EVADE THE IMMUNE RESPONSE.

THE VIRAL SURFACE.

THE SURFACE OF THE VIRUS IS COMPRISED OF A PROTEIN THAT BINDS TO THE
SURFACE OF THE UNINFECTED CELL VIA A SPECIFIC STRUCTURE - THE CD4 MOLECULE.
INTERFERENCE WITH BINDING OF THE VIRUS SURFACE PROTEIN AND CD4 PREVENTS INFEC-

TION.

 

 

 
 

PEOPLE INFECTED WITH THE AIDS VIRUS USUALLY MAKE ANTIBODIES THAT RECOGNIZE
THE SURFACE OF THE AIDS VIRUS. HOWEVER, THESE ANTIBODIES DO NOT PREVENT GROWTH
OF THE VIRUS AND DISEASE.

FEATURES OF THE SURFACE THAT CONTRIBUTE TO EVASION OF THE IMMUNE RESPONSE

INCLUDE:

1. THE SURFACE PROTEIN IS COATED WITH SUGAR MOLECULES. THE SUGAR PROTECTS THE
PROTEIN FROM ANTIBODIES.

2. THE REGION OF ATTACHMENT OF THE VIRUS TO CD4 IS PROBABLY DEEPLY RECESSED IN

is TO
THE SURFACE PROTEIN. ANTIBODIES CAN NOT REACH THE DEEP CD4 BINDING POCKET.

3. MOST OF THE WORKING PARTS OF THE OUTSIDE OF THE VIRUS ARE TUCKED AWAY -

EITHER UNDER THE SUGAR COAT OR UNDER PROTEIN, HIDDEN FROM ANTIBODIES.

THE: VIRUS LIFE CYCLE

aA.

THE LIFE CYCLE OF THE VIRUS ALSO HELPS IT TO EVADE THE IMMUNE SYSTEM. THE

VIRUS CAN INFECT A CELL AND THEN LIE DORMANT, GIVING NO SIGN OF ITS PRESENCE.

oF CELl>
DORMANT INFECTIONS ARE MORE THE RULE THAN THE EXCEPTION.
A

11

 

 
 

 

Y INFECTION OF SOME CELLS RESULTS IN FORMATION OF VIRUS THAT ARE CONTAINED
ENTIRELY WITHIN THE CELL. IF THE VIRUS IS NOT PRESENT ON THE OUTSIDE OF A CELL,

THE IMMUNE SYSTEM MAY NOT SEE IT. THE VIRUS MAY CIRCULATE IN A "TROJAN HORSE"

LIKE STATE, INVISIBLE TO THE IMMUNE SYSTEM.

7 THESE ARE FORMIDABLE OBSTACLES TO OVERCOME. A LARGE SCALE-COORDINATED
ob 24M qo

eR

ADDRESS THESE PROBLEMS HAS BEEN DEVELOPED BY THE NATIONAL INSTITUTES OF HEALTH.
THIS EFFORT IS NOW BEING EXPANDED. Ke DISCOVERY OF A NEWA/ MODEL SYSTEM - THE

Jo

SIMIAN IMMUNODEFICIENCY VIRUS (SIV), WILL BE A GREAT HELP F@R VACCINE DEVELOP-

MENT STUDIES.

CHEMICAL PREVENTION

I WOULD LIKE TO END MY REMARKS ON A POSITIVE NOTE. WE MUST KEEP SIGHT OF
THE GOAL. VACCINES ARE A MEANS TO AN END. THE GOAL IS THE PREVENTION OF
INFECTION. IT WILL SOON BE TECHNICALLY POSSIBLE TO PREVENT INFECTION USING

ANTI-VIRAL DRUGS - IN MANY CASES USING THE SAME DRUGS THAT ARE USED TO TREAT

THOSE ALREADY INFECTED.

THE CONCEPT OF CHEMO-PREVENTION IS THE TREATMENT OF UNINFECTED, HEALTHY/

‘PEOPLE WITH ANTI-VIRAL DRUGS TO PREVENT INFECTION.

12

 

 
 

|

THE FEASIBILITY OF PREVENTION OF INFECTION BY ADMINISTRATION OF ANTI-VIRAL

DRUGS HAS ALREADY BEEN DEMONSTRATED IN TWO RETROVIRUS ANIMAL MODELS. THE

 

CONCEPT OF CHEMO-PREVENTION MAY BE APPLICABLE IN SEVERAL DIFFERENT SETTINGS.

- PREVENTION OF INFECTION OF HEALTH WORKERS AND SCIENTISTS EXPOSED TO
THE VIRUS. NEEDLE STICKS, INJURIES, BLOOD SPILLS AND LABORATORY
ACCIDENTS WILL CONTINUE TO EXPOSE MEDICAL AND SCIENTIFIC PERSONNEL TO
INFECTION. ALTHOUGH THE RISK OF INFECTION IN SUCH SETTINGS IS LOW, IT
IS MEASURABLE. TREATMENTS OF LIMITED DURATION WITH THE ANTI-VIRAL
DRUGS MAY BE PROTECTIVE.

- TREATMENT OF NEWBORNS OF SEROPOSITIVE MOTHERS. THE RISK OF INFECTION
OF INFANTS BORN TO HIV-INFECTED MOTHERS IS HIGH. ABOUT HALF OF BABIES
BORN TO INFECTED MOTHERS BECOME INFECTED AND OF THESE, MANY DEVELOP
SEVERE DISEASE mieain A YEAR. IT IS NOT KNOWN WHAT FRACTION OF THESE
INFANTS ARE INFECTED BEFORE BIRTH on speaveny. IT IS POSSIBLE THAT

LIMITED DURATION WITH ANTI-VIRAL DRUGS COULD SUBSTANTIALLY REDUCE THE

NUMBER OF CHILDREN INFECTED.

13

 
 

 

- SEX PARTNERS OF SEROPOSITIVE PEOPLE. SEX PARTNERS OF SEROPOSITIVE
PEOPLE ARE AT RISK FOR INFECTION. SIGNIFICANT RISK MAY EXIST EVEN IF
“SAFER SEX" IS PRACTICED. IN THIS CONTEXT, CHEMO-PREVENTION MEANS
LONG TERM CHRONIC ADMINISTRATION OF ANTI-VIRAL DRUGS TO THE UNINFECTED
PARTNER.

- HIGH RISK POPULATIONS. CHEMO-PREVENTION - ON A POPULATION BASIS - MAY
BE APPROPRIATE IN POPULATIONS AT VERY HIGH RISK FOR INFECTION. THERE
IS REASON TO BELIEVE THAT IN SOME PARTS OF THE WORLD AND IN SOME
POPULATIONS, THE RATE OF INFECTION EXCEEDS FIVE PER CENT OF THE
SEXUALLY ACTIVE POPULATION ANNUALLY. INFECTION RATES OF THIS MAGNI-

out
TUDE CANNOT LONG BE SUSTAINED WITH ENDANGERING AN ENTIRE POPULATION.

AW
UNDER THESE CIRCUMSTANCES, IN THE ABSENCE OF AN EFFECTIVE VACCINE,

CHEMO-PREVENTION MAY BE ONE OF THE ONLY EFFECTIVE MEANS OF DISEASE

CONTROL.

THE REQUIREMENTS FOR CHEMO-PREVENTION REGIONS ARE STRICT. THE TOXIC SIDE

EFFECTS MUST BE MINIMAL AS THOSE TREATED WILL BE HEALTHY. CHRONIC AS WELL AS

14

 

 
 

 

ACUTE TOXICITY MUST BE EVALUATED, PARTICULARLY IF THE DRUGS ARE TO BE ADMINIS-

TERED FOR A LONG TIME.

‘THE MEANS OF DELIVERY MUST BE SIMPLE. ORAL OR "SLOW-RELEASE" DRUGS ARE

PREFERABLE.’ THE COST MUST BE AFFORDABLE TO INDIVIDUALS AND TO NATIONS.

THERE IS A SENSE OF URGENCY IN THE MATTER OF CHEMO-PREVENTION. AT PRESENT

THERE IS NO EFFECTIVE MEANS TO PREVENT INFECTION OF THE NEWBORNS, OUR NEXT

GENERATION. AIDS VIRUS INFECTION CONTINUES TO SPREAD RAPIDLY AND UNCHECKED IN

LARGE POPULATIONS.

DRUGS, SUCH AS AZT, INTERFERON ALPHA THAT HAVE ALREADY BEEN APPROVED FOR

HUMANS MAY BE USEFUL IN THIS CONTEXT. RESULTS OF CHEMO-PREVENTION COULD BE

OBTAINED WITHIN ONE YEAR OF INITIATING THE STUDY.

SUMMARY

WE ARE NOT HELPLESS IN FACE OF THE AIDS EPIDEMIC. INDEED MANY OF THE

ESSENTIAL TOOLS FOR MEDICAL CONTROL OF THE AIDS EPIDEMIC HAVE ALREADY BEEN

FORGED. MEANS FOR ACCURATE DIAGNOSIS OF INFECTION ARE AT HAND, AND IMPROVED

DIAGNOSTIC TESTS WILL BE AVAILABLE SOON. THE OUTLINES OF A STRATEGY FOR CURA-

TIVE THERAPY HAVE EMERGED, IT IS LIKELY THAT PREVENTION OF DISEASE IN THOSE

15

 

 
 

nT

ALREADY INFECTED WITH HIV CAN BE ACHIEVED PROVIDED ADEQUATE RESOURCES ARE
MARSHALLED. IT IS LIKELY THAT MEANS TO PREVENT INFECTION CAN BE DEVELOPED IN
THE NEAR FUTURE IN THE FORM OF CHEMO-PREVENTION. TO BE SURE, CHEMO~PREVENTION
IS NOT AS DESIRABLE A MEANS FOR EPIDEMIC CONTROL AS IS A VACCINE. NEVERTHELESS,
THE MAGNITUDE OF THE AIDS EPIDEMIC, AN EPIDEMIC WHICH THREATENS ENTIRE POPULA-

TIONS IN SOME PARTS OF THE WORLD, MAY MAKE CHEMO-PREVENTION IMPERATIVE.

16

 

 
 

 

REPORT TO THE PRESIDENTIAL COMMISSION ON HIV INFECTION
18 February 1988
Jeffrey Laurence, M.D.

Department of Medicine, Cornell University Medical College,
New York, NY |

The Immunology of AIDS: Unresolved Questions

I’ve been asked to discuss what is not known concerning the
immunology of AIDS.’ Much, of course, has been discovered about
how HIV, the etiologic agent of acquired immune deficiency
syndrome, affects the immune network. In the five years that
I’ve been involved in AIDS research, much has also been learned
about how the body’s various defense mechanisms attempt to cope
with this invader. Even so, this would have been a considerably
briefer presentation had I simply been asked to review all that
is known about AIDS immunology.

I’ve divided my comments into five areas. (1) The entry of
HIV into immunologically relevant white blood cells: the T
lymphocyte, macrophage, and B cell. (2) The mechanisms by which
certain T cells are depleted. This depletion is arguably the
most important harbinger of an individual’s progression from a
viral carrier state to clinical disease. (3) Early qualitative
immune defects, a period after HIV infection during which cell
numbers may be normal, but cell function markedly curtailed. (4)
The concept of latency, during which HIV is relatively silent
within a cell, yet poised to be converted into a state of active
replication. In this context I’ll raise the idea of cofactors in
the "rescue" of virus from the latent state. Cofactors are

relevant to both experimental models of HIV infection and to pro-

-1l-

 
 

 

 

gression of disease in humans. (5) Finally, I’11 discuss the
body’s responses to HIV, including production of antibodies and
autoantibodies, killer T cells and cell factors.

I. AIDS is initiated by entry of HIV into certain cells.
This process requires a_ receptor. Receptor biology is an
important issue in HIV infection, both in terms of drug or
vaccine development, and in discussions of potential mechanisms
of transmission. Portions of CD4 serve as a point of attachment
for the virus. CD4 is a glycoprotein molecule found on the
surface of helper T cells, macrophages, B lymphocytes, glial
cells of the central nervous system, and perhaps other cells. HIV
binds to CD4 by way of its own coat or envelope glycoprotein
known as gp120. This binding is very strong. Its affinity is
equivalent to that of cCD4 for monoclonal antibodies raised
against it. The troubling issue is that CD4 may not be necessary
or sufficient for entry of HIV into all cells. For example, in
the test-tube HIV can infect cell lines derived from human
colon. Granted, these lines have messages--messenger RNAs--for
cb4, but they are not putting the molecule out onto their
surfaces, at least not in a manner one can detect it. Similarly,
HIV can be introduced into other cells which don’t have CD4,
including endothelial cells which line blood vessels and
Langerhans’ cells of the skin. The gene for CD4 has been cloned
and, when introduced into a human cell, is sufficient to render
that cell infectable with HIV. When introduced into mouse cells,
the CD4 gene also elicits production of high concentrations of
CD4. Yet HIV cannot infect that cell. Clearly, the receptor

-~?-

 

 
 

 

story is incomplete. Preliminary evidence has implicated an
additional candidate, MHC class II (also known as HLA-DR or Ia).
These molecules are much less restricted in their distribution in
the body. They are found on everything from T cells and macro-

phages to activated endothelial cells and intestinal lining

cells. These data are still tentative, as they are based upon
relatively crude antibody blocking studies. But receptor-
independent processes may also spread the virus. T cells

infected with HIV form giant multi-nucleated structures known as
syncytia, and these syncytia appear to be very sticky. That is,
cells without CD4 receptors may acquire HIV as their membranes
fuse with adjacent infected cells. Knowledge about these
determinants are more than just academic exercises. Certain
vaccine strategies, including design of anti-idiotypic
antibodies, rely exclusively on structures that mimic the CD4
receptor. Recently, the cCD4 glycoprotein product has been
produced in abundance from the cloned gene. Its infusion into
patients has been suggested as a possible AIDS therapy, blocking
cell-to-cell spread of virus. This, of course, would only be
valid if CD4 were the exclusive viral receptor. And if soluble
cpD4 did not itself disturb important immune functions. Finally,
hypotheses as to how HIV can and can’t be transmitted are often
predicated on the need for direct interaction of HIV with a CD4+
cell.

Our knowledge as to why certain isolates of HIV infect
helper T cells much more easily than macrophages, or vice versa,
is also incomplete. Some experiments implicating the density of

-3-

 

 
 

 

CD4 on the cell surface have not been supported by other studies.
The type of immune cell infected has relevance to treatment
strategies. For example, AZT is the most potent anti-HIV drug in
clinical use. Yet the concentration of AZT required to achieve a
certain level of HIV inhibition in the test-tube varies with the
type of CD4+ lymphocyte or immortalized T cell line chosen for
study. Even more disturbing is the fact that at least one human
macrophage-like cell line, U937, can be infected quite easily by
HIV, unperturbed by the presence of any concentration of AZT in
its culture milieu. Whether this resistance will hold true for
normal human macrophages is unknown, and must be tested.

II. The mechanisms by which HIV kills cells must be
completely understood in order to design ways of blocking then.
The CD4+ T cell subset encompasses a variety of cells with helper
and inducer immune functions. This subset has been quite
accurately described as a conductor in the symphony of immune
responses which protect the body from infections, cancers and
other foreign invaders. Elimination of this cell type results in
the profound immune defects characteristic of clinical AIDS.
Indeed, there appears to be a direct correlation between the
absolute number of cCD4+ cells and development of AIDS. In one
large cohort study of asymptomatic, HIV seropositive homosexual
men in Los Angeles, 58% with fewer than 100 CD4+ T cells per mm3
developed AIDS within 18 months. Only 4% of asymptomatic men
with greater than 500 CD4+ cells per mm3 developed AIDS within
that same interval.How does this profound cell depletion occur,
and why does it occur at different rates in different

~4-

 

 
 

 

individuals? In the test-tube, HIV can kill CD4+ cells by
inducing the multi-nucleated syncytia I had mentioned earlier.
These structures, which can trap up to 500 cells in one giant
mass, have a limited life span. Certain HIV isolates may induce
syncytia more rapidly than others. Those syncytia related to the
newly described HIV-2 subclass, most prevalent in western Africa,
may take an especially long time to die in vitro. Still, the
phenomena is generalizable to all intact HIV isolates. It is
dependent on expression of the HIV envelope component gp120.
There is great debate as to how important this phenomenon is in
the body, however. Syncytia can be identified in pathologic
specimens, particularly in the brain, liver and spleen, but they
are very rare. It has been postulated that CD4 forms complexes
with HIV envelope intracellularly, and that these complexes are
toxic to cells. However, certain cells which express little cD4
are killed quite efficiently by HIV. Other explanations have
been offered to explain the depletion of CD4+ cells. Suppressor
factors induced by infection of CD4+ T cells may amplify the
virus’s effect, circulating in the blood to inhibit the growth of
uninfected T cells and their precursors in the thymus gland and
bone marrow. Molecules on the surface of T helper cells may
serve as targets for autoantibodies or killer T cells, both
reported to occur after HIV infection. Any or all of these
mechanisms are plausible explanations for the T cell depletion
observed. Conclusive evidence for the importance of any one them
in the body is still lacking, however. Without these data,

rational protocols for immune enhancement are impossible.

-~5-

\

 

 
 

 

III. Depletion of T helper cells, and consequent reversal of
the CD4:CD8 helper-to-suppressor, T cell ratio, is the most
obvious laboratory manifestation of AIDS. . Yet profound
immunologic defects, found in the body and duplicated.in the
test-tube, occur early after HIV infection, prior to any
measurable T cell depletion. This stage of HIV infection,
conceivably more amenable to intervention, requires, much closer
scrutiny. Examples of such early defects include the inability.
of an individual to respond to skin test antigens in a reaction
known as delayed type hypersensitivity, failure to generate
specific antibody in a vaccine challenge, and inability of T
cells to proliferate after exposure to foreign antigens. These
abnormalities are often independent of CD4+ T cell number. In the
test-tube they are not correctable by addition of T cell factors
such as interleukin 2 (IL-2), or inclusion of macrophages or
other accessory cells from non-infected individuals. Why does
this occur? There is evidence that the initial steps of antigen
recognition by T cells are intact. Infected T cells respond in
certain ways to foreign signals, even if they can’t proceed along
the full cascade which describes normal T cell function. The
exact nature of the barrier .to complete responsiveness is
unknown. Macrophages, one type of cell which can process
antigens and "present" them. to T cells, may he involved.
Macrophages are qualitatively and quantitatively disturbed in HIV
infection. The range of these abnormalities is large, although
certain investigators question their significance to clinical

disease. For example, .in many systems T cell defects

-~6-

 

 
 

 

are independenof macrophages. The contribution of macrophages,
and other antigen-presenting cells, is a distinct issue which
also requires further work. Finally, there are gaps in our
knowledge of the way HIV interferes with different pathways of T
cell activation. Alterations in an important T cell growth
factor, IL-2, without changes in a cell’s receptors for that
hormone, have been identified. However, adding IL-2 in the test-
tube has little beneficial effect. Indeed, in certain systems it
May worsen the immune deficit. IL-2 has been used to treat
patients with AIDS in experimental studies at the NIH and
elsewhere. It has shown little efficacy, and has been linked to
an unexpectedly high incidence of serious infectious compli-
cations. Another disturbing issue is that many of the signals,
both antigen dependent and antigen independent, with which one
would like to stimulate an infected T cell may instead provoke
that cell to begin actively replicating virus, and eventually to
self-destruct. This leads directly into the topic of viral
latency, and questions as to the ways in which dormant virus is
converted into productive infection.

IV. One of the more puzzling aspects of AIDS is the profound
disturbance of immune function that occurs in the face of what
appears to be very low levels of viral replication. Currently
available techniques to detect virus-associated nucleic acid,
known as in situ hybridization, demonstrate RNA or proviral DNA
in less than one in ten-thousand target T cells or macrophages in
blood or other tissues. It has been postulated that HIV-induced
cellular factors, or gp120 shed from these few cells, greatly

-7-

 

 
 

 

amplify the effects of a limited infection. These phenomena
cannot be demonstrated in all patients, however, and _ the
concentration of viral gpl120 required to produce an immune
deficit in the test-tube is orders of magnitude greater than what
is detected in the body. It now appears likely, albeit by no
means proven, that many more cells are infected in the body,
persisting in a dormant or latent state. These cells, producing
very little viral protein or nucleic acid, and not actively
replicating HIV, escape detection. Indeed, lacking a foreign
protein target on their surface, they may not only escape
detection by our hybridization assays, they may also escape
whatever host mechanisms of viral clearance have been left
intact. Evidence supporting this theory comes from serial
examinations of T cell cultures exposed to very low levels of
virus. The viral signposts one commonly searches for--reverse
transcriptase activity, proteins, RNA--are not apparent, unless
one further perturbs the. system. Foreign antigens which the T
cell had been primed to recognize, artifical plant lectins such
as PHA (phytohemagglutinin), chemicals such as PMA (phorbol
ester), or other viruses can all stimulate T cells, and
concominantly activate the virus, within a short period of time.
Active viral replication can now be quite easily demonstrated, as
the latent HIV has been "rescued," or converted into a productive
state. If one makes an analogy between this system and the
situation in humans, many more lymphocytes and macrophages are
almost certainly infected with virus than can be found by what

are currently our most sensitive detection techniques.

-~8-

 
 

 

Latency makes alot of sense from a virus’s point of view. It can
remain dormant and slowly propagate along with its host cell. As
long as limited amounts of envelope protein gp120 are made, it
will not kill the cell. The mechanisms by which HIV remains in
this state are complex. They involve several genes which alter
viral replication either by so-called cis-acting (e.g., the NRE
(negative regulatory element) region) or trans-acting (e.g., tat
and art) mechanisms, as well as one gene with diverse functions
(3’-orf). This is outside of the scope of a talk on immunology.
What is relevant is how Signals as diverse as a herpesvirus or a
plant molecule can activate latent virus.

There are certain sequences in a region of the HIV genome
known as the 5’-LTR which serve as targets for viral and cellular
regulatory factors. Binding of these protein molecules to this
region markedly enhances the transcription of HIV. This region
is sensitive not only to HIV’s own proteins, known as trans-
acting molecules, but to those induced by many T cell activation
signals. What we don’t know is the relevance of these cofactors
identified in the test-tube to enhancement of HIV replication in
humans. It is also unclear how one might design drugs that could
interfere with HIV activation, without simultaneously
interferring with activation of normal T cells attempting to
combat the infection. The importance of this phenomenon to the
immunology of AIDS may be illustrated by two recent, and very
public examples.

A small, uncontrolled clinical trial of the T cell immune
-~9-

 

 
 

 

suppressant cyclosporine was undertaken by a French group two
years ago. One rationale was that HIV replicates actively

only in stimulated T cells. Cyclosporine, by blocking this
stimulation, might thereby retard the spread of HIV to uninfected
lymphocytes. We now know that cyclosporine inhibits only one of
the many pathways by which T cells become activated. This is
technically known as the CD3-Ti pathway, and responds to
stimulants such as PHA and antigen. In test-tube experiments
using the HIV 5’-LTR, cyclosporine did indeed inhibit signals
linked to CD3-Ti, but not those associated with several other
activators.

Secondly, there has been much attention paid to possible
infectious AIDS cofactors. The very variable and, in some
instances, very long or indeterminate interval between infection
with HIV and development of AIDS has been linked epidemiologic-
ally to intercurrent viral infections. One of these infections
is HTLV-I. HTLV-I, like HIV, is a human retrovirus which homes
in on T cells. Rather than killing T cells, however, it leads to
their immortalization. A small percentage of infected
individuals will develop a T cell cancer, either leukemia or
lymphoma, after an incubation period that is measured in decades.
Most people remain healthy. In Trinidad, where a high incidence
of both HIV and HTLV-I infection exists, comparisons were made
between the development of AIDS in asymptomatic homosexual men
infected with HIV alone versus HIV plus HTLV-1. Of 34 men
infected with HIV alone, 9% developed AIDS within a four year

surveillance period. Of six men infected with both retroviruses,

-10-

 

 
 

 

, 50% developed AIDS within that interval. The numbers are small,
but the difference was highly significant statistically. The
phenomenon deserves close attention as in Trinidad only 6% of
their HIV infected individuals also harbor HTLV-I. The situation
is quite different in the United States. In one borough of New
York (Queens), this figure was 27% of all drug abusers screened.
In one city of New Jersey, it was 16% of all drug abusers
screened. Granted, HTLV-I is a rare virus, and dual infection in
the U.S.is probably limited to drug abuse populations of certain
inner cities. But the phenomenon of HIV activation following
exposure to products of other infections is not limited only to
HTLV-I. In the test-tube, it can occur with herpes simplex
virus, cytomegalovirus, and hepatitis B virus, all very common
microorganisms. And these are only the ones that have been
tested. Other experimental viral activators may also be relevant
to human disease. The potential risk of immunization of HIV
infected persons has been raised. In one case report, smallpox,
quickly followed by AIDS, developed shortly after vaccination of
an asymptomatic, HIV seropositive Army recruit with attenuated
smallpox virus. Statistically, this and other anecdotes are
insignificant. I would still argue that these are important and
unsettled issues. The HIV/HTLV-I data, and analogies with test-
tube activation of infected T cells, must be carefully explored
in clinical studies prior to the widespread institution of
experimental AIDS treatments, be they immune modulators such as
IL-2, recommendations of "hypervaccination," or HIV vaccines.

Paranthetically, these preliminary immunologic findings also

-11-

 
 

 

 

suggest avenues for improved HIV detection. Cell activation
combined with more sensitive viral assays, such as the PCR
(polymerase chain reaction) DNA amplification technique, could
represent a valuable joining of immunology and virology. It might
help to resolve the issue as to why techniques such as PCR alone
could not detect HIV in some 40% of cultured cell samples derived

from HIV seropositive individuals.

V. Against these odds one might think the host’s immune
defense is totally effete, but this is not the case. Humoral and
cellular immune responses directed against HIV and its products
do occur. Their relative efficacy, and how they might be
amplified, are important unknowns. Serologic responses to HIV
envelope and structural components have been extensively charted.
The relevance of certain patterns which appear to distinguish the
asymptomatic carrier state from AIDS-related complex and AIDS
remains controversial, however. Newer insights have been gained
by examination of antibody responses to enzymatic activities of
the virus, but these associations are also tentative.

In terms of serologic information of use for vaccine
development, it is unclear whether the consensus sequences of the
viral envelope recognized by immunoglobulins from most infected
individuals have any relevance for fighting the infection in the
body. Most neutralization assays performed in vitro correlate
very poorly, if at all, with the clinical situation. Until the
appropriate neutralizing epitopes are defined, vaccine strategies

may not be much more than "hit-or-miss" struggles.

-12-

 

 
 

‘It is also possible that antibodies play much less a

protective role than do killer T cells primed to recognize and

destroy HIV-infected targets. These cytotoxic lymphocytes, which

bear surface molecules known as CD8, can be demonstrated in many
infected individuals. They are most easily found at the early
stages of “disease. Vaccine strategies which attempt to
incorporate both a B cell (antibody) and T cell (cytotoxic)
component may have the best chances for success. Of course, more
work in defining exactly what parts of the virus the cCD8
lymphocte "sees" is necessary.

Other types of immune cells, including those involved in
antibody-dependent cell mediated cytotoxicity (ADCC), natural
killer cells, and macrophages, as well as their soluble
mediators, the interleukins and interferons, deserve more
attention. Finally, potential synergies between anti-viral drugs
and these immune cell mediators must be explored in a systematic
manner. A concerted effort aimed at joining the expertise of
virologists and immunologists in examining the myriad effects of
HIV on the immune network can only facilitate development of the

anti-HIV drugs and vaccines we all urgently seek.

-13-

 
 

 

Testimony of Drs. Dierig and Waldthaler

   
   

TESTIMONY DELIVERED TO THE PRESIDENT'S COMMISSIO?
SSBRUARY 13, 1988 (SECTION IMMUNOLOGY )

 
  
 

I hope you don't mind if our English is far from being

We are anaestheslologists with an office in Augsburg, ea
Germany. Both of us spent years in an intensive care unk

Zarly in 1981, we treated a bisexual patient with a history o
venereal diseases for possible sepsis. Since all blood cultures
were negative, we decided to treat him with high dose IV
Penicillin-G. The patient recoverad within three weeks.

Wnen the test for LAV/HTLV III became available in early 1985, we
tested the patient to rule out any possible connection with the
Acquired Immune Deficiency Syndrome. The tes= vas positive. This
led us to treat more HIV nositive patients. Ten treatments in Six
oatients were performed. Five patients are in excellent clinical
conditions; one patient died during treatment because of pulmonary
complications.

Clinical manifestations attributed to HIV infection disanneared.
So we tried to correlate the immunosuporession attributed to HIV

infection with immunosuppresion known in Syphilis.

“nat we oresent here as clinicians is not a study, neither
randomized nor double blind but a report of immunological changes
by penicillin treatment of HIV positive patients.

Laboratory data and some interpretations are as follows:

In lymphocyte subponulations no particular changes were noted with
B and NK cells.

T4 (nelper/inducer)-cells: In three cases an increase was seen,
for example, from 93 to 383 per microliter and from 205 to 774

per microliter, in other cases an initial decrease and an increase
after two months.

TS (suppressoc/cytotoxic)-cells: In four cases we noted an
increase, for examole from 956 to 1310 per microliter, in other
cases a decrease for example from 905 to 344 ver microliter. Akt
the moment we are unable to differentiate between Suppressor and
cytotoxic cells¥but clinical improvements (for example the
resolution of lymphadenopathy, skin problems and Herpes Zoster)
Suggests that the increase in T3 numbers may be due to an increase
in cytoxic cells numbers.

Lymphotcyte mitogenesis assays with PHA, Con A and PYM all
improved in three casas where chey were perforned, esnecially with
PHA. The impaizment of lymphocyte resoonse to PHA is well known
ig, syphilis, where acidic mucopolysaccharides coat immunocompetent
cells inhibiting either cell to cell contact or the binding of
mitogens to cell receptors.

 
 

 

ing immun2 toaplexes (CIC) of IgG and IgM class: In the
where analses of CIC's revealed presence of treponemal
antigens, the CIC's dropped significantly.

OQ &
—
ju
cv

Lysozyme: Increases were noted in all cases where it was
measured; in one case, the increase was over two hundred fold.

Beta-2-microglooulin, which is a loosely bound part of the major
histocompatibility complex 1, in our patients remained above
normal range. The variable region of gp120 of HIV imitates
antigenic structures of MHC 1. Treponema pallidum acquires MHC 1
antigens of the host. It should be discussed which of the two
mechanism is responsinle for the increased level of Beta-2-
microglobulin in HIV positive patients.

vitamin Bl2 and folate where measured because of anemia with high
MCV, hypersensitivity to TMP/SMX and an increase of T4 and B cells
after administration of potassium iodide. Vitamin Bl2 increased
after therapy while total folate renained unaffected. In our
analysis it was not  ,ossiole to differehiate between dihydrofolate
and tetrahydrofolate. Since treponema pallidum are not
suscentible to sulfonamides and do not incorporate thymidine, they
are dependent upon the folate cycle of the host. Trimethoprim
Locks the dihydrofolate reductase while potassium iodide and
heavy metals stimulate this enzyme. This could exolain on the one
nand the adverse reactions of HIV positive patients to
trimethoorim and on the other the effect of potassium iodide and
heavy metals in the treatment of syphilis. It is wortn mentioning
that potassium iodide was used for treating syohilomas and had
some effect on Kaposi's sarcoma, as do high doses or IV

penicillin.

A dilution of the HIV Zlisa test was done in two cases. In

borh cases the titers dronned dramatically. In one case it
dropped from 1:327,680 to 1:5,120, in the second case, it dropped
from 1:2,621,440 to 1:19,240.

Finally a word on syphilis serology. After therapy we found an
overall decrease in the most sensitive test, the TPHA and an
increase in the most specific test, the IgG-FT -Abs. After five
treatments the VDRL test turned vositive. In one case the TPHA
and FTA tests, which had been positive for over 20 years, turned
negative after treatment.

In conclusion: Many of the clinical manifestacions and
immunological disorders attributed to infection with HIV are
indistinguishable from those found in the course of infection with
treponema pallidum. As of this day, no definite nathomechanismn
has been found for any of the symptoms of syphilis. Since
syonilis serology in HiV posicive patients is noc reliable and
Since there exists no criterion for adequate therapy, esvecially
of late syphilis, it is imperative to rule out syphilis by all
means in an HIV nosizive natient.

 

 

 
 

 

PAGE THREE:

We conclude that:

1. A positive VDRL means active Syonilitic infection.

2. A negative VDWL with a positive crenonemal test means
presence of treponemal antigen.

3. A negative VDRL and negative treponemal test do not exclude
treponemal infection because specific antibodies may be
hidden within CIC's and antibody svecificity is lost over
time.

4. Monoclonal antibodies may prove more helpful to diagnose
Syphilis. ow ruler del Uyfrrdiga tion My proved rn red hth fr Q

5. The safest way to rule out treponemal infection would be
diagnostic treatment.

Mr. Chairman, Members of the Commission, we appreciate the
invitation to present this information to you today and we hope
that it may contribute to a better understanding of some aspects
oi the HIV enidemic.

Recommendations for consideration by The Commission:

We suggest an investigation of which role trenonemal infection
Dlays in the HIV epidemic by:

1. Accelerated basic treponemal research on the interaction of

treponema pallidum with:
a. Mitrochondria (VDRL test; anemia in HIV Dositive
vatients).
®. Vitamin Bl2 and folate metabolism (anenia,
tarombocytovenia, reduced blastogenesis of immunocompetent
cells, demyelinating disorders and hypecsensitivity to
TMP/SMX in HIV positive patients).
Cc. Beta-2 microglobulin.
ad. Band plasma cells (Russell's bodies are Found in both
KS and syphilomas).

2. New diagnostic approaches in order to detect treponemal

antigen in:
a. Circulating immune complexes.
b. KS by indirect immunofluorescence microscopy.

3. Making available facilities to treat HIV positive patients
with high doses of IV penicillin-G (20 million units
continuously IV over 28 days). NOTE: Detailed information
about the regimen and results of its apdlication is being
prepared for publication.

~
It seems imperative that we reappraise the diagnostic ‘procedures da tas,
@f treponemal infections in the antibiotic era and redefine (O43 ag
“adequate treatment",

Klaus-Uwe Dierig, M.D. | Urban Waldthaler, M.D.
Herrgottsberg 23 An Brunnenfeld 7
D 8901 Stadtvercgen D 8902 Neusass

West-Germany Wesc-G 2omany

 

 
 

 

Testimony of Dr. A. Arthur Gottlieb

TESTIMONY BEFORE THE PRESIDENTIAL COMMISSION
ON HIV INFECTION

FEBRUARY 18, 1988
NEW YORK CITY

Ladies and Gentlemen:

I am Dr. A. Arthur Gottlieb, Professor and Chairman of the Department of
Microbiology and Immunology, and Professor of Medicine at the Tulane University
School of Medicine, and Chief Executive Officer of Imreg Inc., a publicly held
biotechnology company. I appreciate the opportunity to appear before you today
and to give you some of my views on drug development in AIDS/ARC. My comments
reflect my perspective and experience at the academic-industrial interface, and
as the inventor and developer of IMREG®-1, an immunosupportive biologic.

I have presented to you a position paper by myself and Dr. Robert F. Garry,
Associate Professor of Microbiology and Immunology at Tulane. For the moment, I
wish to summarize some of the points made in that position paper. I might say
that Dr. Garry's expertise is in virology, and that he and I were responsible for
confirmation of the case of HIV infection that was seen in St. Louis in 1968, and
is to our knowledge the earliest documented case of AIDS in the U.S.

The principal message I woud tea you with today is that the national
effort directed to treatment of AADS/ARC needs to place preater emphasis on ways
and means to correct the state off immune deficiency seen in patients with this
disease. There is a need to présexve this objective with at least the same
commitment as is being directed to the antivirals. It appears that some interest
is developing in this area, but to date the development of immunosupportive drugs
has clearly had a lower priority.

The emergence of HIV infection as a major world health problem is at once a
challenge to the scientific and medical communities as well as a vindication of
the investment which has been made in basic immunologic research over the last
two decades, for without that information, our ability to understand and deal
with this disease would be nil. The characteristics of the devastating disease
states, AIDS and ARC are widely known, but it is well to emphasize that a princi-
pal feature is a defect in the capacity of the patient to mount immune reactions
to specific antigenic challenges, as a result of selective progressive destruc-
tion of critical regulatory cells (T helper cells).

There are a variety of associated immune phenomena which occur in HIV
infected individuals, and in a very real sense, this condition should be viewed
as an acquired dysregulation of the immune system, the most prominent feature of
which is a deficiency in the ability to mount specific immune responses. Re-
versal of these serious and complex immune dysfunctions does not occur sponta-
neously, and the disease in its advanced form has a high degree of fatality. The
emergence of AIDS as a world public health problem of major dimensions poses a
need for intense and comprehensive attention to all possible approaches to the
treatment of this infection.

We now recognize that the original definition of AIDS, as promulgated by the
Centers for Disease Control, was very narrow and reflected only a minor fraction

 
 

 

of the range of clinical and immunologic phenomena seen as a result of HIV
infection. It is more logical to regard infection with HIV as being able to
cause a deficiency of the immune system to a variable degree in each patient who
is infected. That is, some individuals who have been infected with the human
immunodeficiency virus (HIV) (previously referred to as the LAV/HTLV III) will
have little compromise of immune function, while others will have a severe
deficiency, and many will fall in between. In general, the more severe the
immunodeficiency, the more likely the patient will experience the serious clini-
cal complications of opportunistic infections and malignancies.

The most advantageous time to treat a patient with an immunosupportive drug
is at the early stages of appearance of functional immunodeficiency.

It should be noted that although substantial information has been developed
about the Human Immunodeficiency Virus, and the fine structure of its genetics,
relatively little is known about the way in which this virus damages cells of the
immune system and thereby leads to disease. We need to develop much more
information concerning the pathogenic effects of the virus on the immune system
at both a cellular and molecular level, and the regulatory abnormalities that
result from HIV infection. For example, we have little information about the
cells that are needed to trigger immunity against this virus, and we remain
puzzled as to why initial infection leads to circulating antibody which is not
protective.

In thinking about approaches to treatment of HIV infection, two initiatives
come to mind:

(1) Development of anti-viral drugs that will suppress production of new
HIV virus, or prevent infection of healthy lymphocytes by that virus, it
being recognized that no technological means for eliminating the virus from
the host DNA is possible, at the present time, or seems likely to be devel-
oped in the next decade.

(2) The development of biologics and/or drugs that ameliorate or modify the
state of immune dysregulation with predominant immunodeficiency that is the
hallmark of this disease. There is developing evidence that support of the
immune system is possible in these patients. In my view, too little atten-
tion is being paid to this critical aspect of the problem. It is surprising
that the repair of the immune deficiency in AIDS/ARC has, to date, been
considered to be the least important aspect of treatment and control of this
infection.

We submit that while extensive efforts have been undertaken in the area of
development of anti-viral agents, there is too little effort being directed
toward a comprehensive understanding of the pathogenesis of this disease, and the
effects of HIV on the immune system. Such information would, of course, also be
critical to development of vaccines. Moreover, in our judgment, there has been a
lack of appropriate emphasis on the development of drugs and/or biologics which
can _ modify or repair the immune deficiency. The drug development programs
currently underway are weighted too heavily in the direction of anti-viral
therapy. While there are some initiatives being undertaken in the area of
immunosupportive drugs, the basis on which drugs of this type have been selected
for testing under the NIH drug development programs has been unclear.

 

 

 
 

A consideration of importance as regards the development of immunosupportive
or immunoreconstructive drugs is the apparent ability of the immune system of
patients with HIV to undergo a process of immunologic compensation. For example,
some patients with HIV infection manifest normal functional immune responses,
notwithstanding an absolute reduction in numbers of their CD4+ (T helper) cells.
What appears to happen in these instances is that the remaining cells work harder
to "take up the slack." While the remaining cells are capable of doing this, the
immune system maintains a normal or near normal level of function. However, as
more CD4+ cells are destroyed, the compensatory capacity of the remaining cells
becomes compromised, and immunological function declines. If a drug or biologic
could stabilize a compensated immune system or prevent decompensation, that would

likely be beneficial for the patient.

In this context, the development of drugs/biologics capable of moving a
patient's immune system from a state of immune deficiency to one of more normal
function would likely have an impact on this disease. Such a drug/biologic would
not be a cure, since it would not eliminate the virus, but it could control some
of the manifestations and course of the disease.

The specific rational for an immunosupportive drug in HIV disease is as
follows:

(1) A principal feature of the disease is an immune deficiency.

(2) Although it is possible to design a program for development of anti-
viral drug(s) for widescale application to all HIV infected individuals,
such drug(s) are not presently available. The anticipated timetable for
such drug(s) is a minimum of five years, with time frames out to fifteen

years.

(3) It is clear that correction of the immune defect is a desirable objec-
tive, and it is reasonable to anticipate that improving immune function
would reduce the frequency of opportunistic infections, and possibly malig-
nancies in HIV infected patients.

While it is claimed in some quarters that an "effective" anti-viral would
eliminate the necessity for an immunosupportive drug, since the immune system
would regenerate on its own, it is important to point out that the ability and/or
the period of time required for the CD4+ cell population (or progenitors thereof)
to be reconstituted in adequate numbers and function, once viral production is
suppressed, is unknown. In this respect, attention should be paid to the possi-
bility that bone marrow progenitor cells may be latently infected with HIV, and
that such latent infection may well affect the ability of such cells to
adequately reconstitute the immune system.

A further important consideration is the prospect that a drug having sup-
portive effects on the immune system might enhance immune reactivity against
strains of HIV virus which infect particular patients. That is, this might
provide a means for enhancing the ability of the patient’s immune system to react
against the particular viral strains which have infected the patient. This
concept of post-infection vaccination, which is possible owing to the long latent
period seen in this disease, has been advanced by several researchers, and is an
initiative that should be vigorously addressed, since:

-3-

 

 
 

 

(a) it might provide a means for possible protection of patients who have
already been infected with HIV,

(b) it would be an extremely useful ancillary to a vaccine, if a vaccine
were developed,

(c) it would reduce the need to come up with effective vaccines against
multiple viral strains.

The development of immunosupportive drugs or biologics should be viewed as
complementary to the development of anti-viral drugs for widescale application to
HIV infected individuals. As developments proceed to find drugs which suppress
production of new HIV particles and/or prevent infection of healthy CD4* cells by
new viral particles, it is important to keep in mind the requirement that such
drugs must be free of significant toxicity on either bone marrow precursors of
immune cells, or on effector cells of the immune system. To date, we believe
that there has been too great a concentration of effort on developing anti-viral
therapy, and too little emphasis on learning about and correcting the disorders
in immune function which are manifested in variable degrees in HIV infected
patients.

I would now like to describe a case in point of development of an immuno-
supportive biologic.

If one views the history of biological response modifiers beginning with the
interferons (late 50's) to the interleukins (mid 70's), the general approach has
been to take these substances which had been found to have effects on viruses or
immune cells in the laboratory and use them clinically to see if they had desir-
able effects.

The approach we have taken is to extract from cells of the immune system
(generally, white blood cells) substances which could be shown in human test
subjects to have important effects on the immune system -- in particular, sub-
stances that could strengthen the body’s response against foreign substances such
as tetanus toxoid (vaccine). We were able to systematically identify, isolate,
purify and patent a group of such substances, one of which has now been
designated as IMREG®-1. The immunologically active components of IMREG®-1 have
been shown to be chemically related to the enkephalins, a group of important
neuropeptides peptides. I might say that these developments began in 1980, and
that it was necessary to look to the capital markets for the necessary commitment
of financial resources over a reasonable period of time, in order to take these
initiatives forward.

Our concept was that these naturally-occurring immunoregulators might be
useful in diseases such as cancer, rheumatoid arthritis and other conditions in
which a disordered immune system plays a role in the disease. From the outset,
these substances were know to affect cell mediated immunity and therefore, it
seems reasonable to suggest that they might have potential as clinical
therapeutics. When we started, AIDS had not surfaced as the major public health
problem that it is today. Indeed, it was only as a result of the recommendation
of our Company's Scientific Advisory Board that we began to use IMREG®-1 in
patients with AIDS/ARC, and we in fact had to divert resources from other
initiatives in order to address the AIDS problem. We treated the first patient
in 1983 and returned his ability to mount specific immunity In 1984, we began

-&-

 

 
 

 

larger studies which necessarily involved the absence of a placebo controls, as
we were looking for some effect on immunity and needed to assess toxicity. We
did see important effects on immune function, as well as clinically important
parameters. In particular, these studies showed:

(1) Restoration of delayed hypersensitivity (capacity to respond to antigen
injected under the skin) in more than 50% of patients who were unresponsive
before treatment with IMREG®-1.

(2) Patients treated biweekly gained an average of tl.ree pounds.

(3) A decrease in the rate of destruction of CD4+ T helper cells in pa-
tients treated biweekly.

(4) No toxicity was observed and there were no deaths on study.

Since patients at this stage of HIV infection display a progressive downhill
course, we felt that the investment of our time, effort and the Company's money
in a multicenter placebo-controlled trial of IMREG®-1 in AIDS/ARC patients was
justified, and could not wait for application to an negotiations with NIH for
support of such 4 trial, although an offer of cooperation from NIH would not have
been declined Accordingly, such a trial has been undertaken, and has
essentially bicn ceonpleted. One hundred fifty (150) patients have been enrolled
and rapdovrized in @ 2°1 fashion. Ve e»pect to have the results of this trial and
a judgesent of the efficacy of IMREG®-1 in AIDS/ARC will be made by an
independent review group by the end of Maich

Toricht say that these developtrents have been undertaken cempletely on our
own resources, ang in perticular, not a singie penny of federal support hes been

ett TES plate cee eg
Secondly, we have been able to conduct a plscgbc-controlied trial in this
disease. One reason we were able to do so is thacy the trial protocol calied for
providing iMREG®-1 for six months to any patient who completed the trial, or
reached an endpoint. We are now confronted by a very difficult question.
Several of these patients who have completed the 6 month compassionate course
(following their participation in the 6 month trial) are asking that they be kept
on treatment. We do not have permission from FDA to do this, and we would hope
that under the new federal regulations pertaining to experimental drugs, the FDA
will see fit to permit these patients to continue to be treated.

 

 
 

PRESIDENTIAL COMMISSION ON THE HUMAN IMMUNODEFICIENCY VIRUS EPIDEMIC
Statement of
Dr. Richard S. Ross
Dean of the Medical Faculty
Johns Hopkins University School of Medicine

February 18, 1988

The medical schools and universities are ideally suited to become the
focus of major comprehensive programs directed at the control of the HIV
virus epidemic. The programs should include public health education and,
hence, the universities with both medical schools and schools of public
health have special strengths. Clinical investigation to include evaluation
of therapeutic agents is another area in which medical schools and teaching
hospitals have unique expertise. Basic retroviral research must also proceed
at a more rapid pace if new drugs and vaccines are to emerge for clinical

trial.

The medical schools have people who have the necessary skills and
interest in all these areas, and more importantly, can attract and train
others. The limiting factor is lack of space. None of the excellent
academic medical centers have space available in the quantity necessary to
mount a comprehensive program. New space of a very special sort must be
provided if the pace of research, education, and patient care for AIDS

patients is to accelerate.

I propose that the comprehensive cancer center program of the early 1970s
be taken as a model for a HIV centers program. Four or five HIV centers
would be constructed in conjunction with major academic medical centers.

Each center would have programs in prevention, education, clinical care,

 

 

 
 

 

clinical investigation, and basic retrovirus research. Such centers would
provide a critical mass of experts in these various areas, and the
interaction between the various groups would be extremely productive.
Problems arising in patients could be taken to the laboratory for solution,
and ideas developed in the laboratory could be brought to rapid testing in
the clinic. The centers should be bound together by a coordinating mechanism
so that concerted action could be directed at specific problems. for
example, a new drug could be subject to trial using the same protocol in all
the centers. A large number of patients could be studied in a short period

of time by the same method and questions answered more rapidly.

Not all the available funds should be allocated to the comprehensive
center program. An approximately equal amount should be made available to be
allocated to institutions proposing quality research programs in one or more,
but not all the areas in the comprehensive centers. For example, it should
be possible to provide funds for the creation of a new P3 laboratory to

encourage an established virologist to enter HIV research.

In summary, the critical need is for facilities, both comprehensive
centers as well as other laboratories, associated with academic medical

centers.

 

 

 
 

 

GMIC

The AIDS Service and Education Foundation

Testimony
Presidential Commission on the HIV Epidemic

Barry Gingell, M.D.
February 19, 1988

I have been asked to discuss my personal involvement with AIDS
drug development and access. I am aéephysician and am
currently the Director of Medical Information for Gay Men's
Health Crisis, the nation's foremost private organization
providing patient services, education and advocacy for people
with and at risk for AIDS. For several years, I was a primary
care physician and have treated many patients with AIDS and
ARC. Over three years ago, I myself was diagnosed with AIDS.

My diagnosis in January, 1985 was, of course, a great shock to
me. But, being a physician, I felt that I had a better-than-
average chance of beating AIDS. I thought I would be able to
access clinical trials and experimental drugs easily. I knew
that some progress was being made in the search for effective
antiviral drugs. But much to my dismay, I soon discovered
that my search for experimental drugs would not be easy. I
had waged a successful battle with PCP pneumonia, but the next
hurdle, accessing antiviral and/or immune modulating
therapies, proved infinitely more difficult.

I discovered that there was no centralized registry of trials
of AIDS drugs, and so my search for appropriate clinical
trials took the form of an endless series of telephone
inquiries to researchers across the country. I was promised
that I would be first in line for two different trials, one
with Ribavirin and one with Foscarnet, in the Spring of 1985.
By September, neither of the trials materialized, and I knew I
was losing precious time. I learned that Ribavirin, a drug
which was shown to have activity against HIV in vitro one year
earlier, was available essentially over-the-counter in Mexico.
And so I joined the other hundreds of patients in Tijiuana to
smuggle in a drug that I hoped might stop the progressive
damage that I knew was occurring to my immune system.

I was successfully maintained on Ribavirin for over 14 months
without serious opportunistic infection. When AZT became
available on a Treatment IND, I opted for it instead of
Ribavirin, primarily because of the easy availability and
apparent superior antiviral activity.

Gay Men's Health Crisis Box 274,132 West 24th Street, New York, New York 10011 212°807°7035

 

 
 

 

We now know that AZT exacts a very expensive. price, both
financially and in terms of toxicity. The magnitude of this
toxicity is increasing with time. A recent study on the
original cohort of AZT recipients who took the drug for .one
year provides us with the sobering figures: fully 404 of
patients experiénce serious hematologic toxicity after one
year, and 25% have to be discontinued entirely. The magic
drug Retrovir which has been foisted on the public as a
triumph against AIDS is actually turning out to be a
cumulative poison. While it may prolong life in the short
term, AZT creates its own set of serious hematologic problems,
which may in fact contribute to the disease rather than
moderate it.

Yesterday, none of the testimony focused on the _ serious
limitations of AZT, and I feel that they need enumeration.
First, as I have mentioned, AZT causes serious bone marrow
suppression, resulting in lowered red and white cells in the
blood. AZT-induced anemia is becoming quite commonplace, and
some have expressed fears that the increasing number of
transfusions associated with AZT may put a serious strain on
the nation's blood supply. AZT-induced neutropenia may be a
contributing factor for the increasing numbers of bacterial
infections now being seen in AIDS. Second, AZT works at a
stage of viral replication after binding of the virion to a
susceptible lymphocyte. As mentioned in previous testimony,
cell-to-cell transmission is an important way in which HIV is
spread within the body. AZT has no effect on blocking cell-
to-cell HIV infection. Third, it has been- recently
demonstrated that AZT is not effective in the monocyte-
macrophage because this type of cell lacks the enzymes
necessary to activate the drug. Thus, this cell which is
already thought to be a reservoir for virus in the body,
actually protects the virus within it from inhibition by AZT.

Because of these serious shortcomings of this drug, AZT should
actually be considered only a prototype antiviral drug.
However, fully 80% of patients in NIH-sponsored clinical
trials are taking AZT. At the same time, many drugs which
have shown promise either in in vitro studies or limited pilot
studies and are less toxic than AZT are being ignored.

Ribavirin, the drug which I procured in Mexico in 1985, was
shown to have in vitro anti-HIV activity in November, 1984.
From preliminary studies (none conducted at NIH), Ribavirin
seems to be less toxic than AZT. Why has it taken over 3
years to get a definitive study of this drug underway? What

 

 
 

 

does this kind of delay say about the process by which we are
evaluating potential AIDS therapies?

A similar in vitro observation was made for AL721 in October,
1985 by Dr. Gallo at the NIH. This anti-HIV activity has
since been confirmed by Dr. Laurence, who delivered testimony
during yesterday's session. AL721, actually a food substance,
seems to have no toxicity whatsoever. Yet these and other
promising drugs are being overlooked by NIH while they
exhaustively study their crude first attempt, AZT. These
follow-up studies of AZT could be easily financed and
conducted by Burroughs Wellcome which is making money hand
over fist with the drug. Why are we devoting precious
government resources on studying every conceivable aspect of
AZT when we know its critical limitations? Why, at the same
time, are other drugs are caught up in endless red tape or
stymied by petty quarrels between pharmaceutical companies and
governmental agencies?

As is typical for people taking AZT in the long-tern, I
reached the end of the road with the drug less than one year
after starting it. Eight months after beginning AZT, my white
cells progressively decreased to dangerously low levels
despite dose reduction and culminated in a bacterial pneumonia
which almost cost me my life. Since there is no alternative
antiviral available to me, even through a clinical trial, I
again have found myself in the situation I was in three years
ago: searching for available, hopefully safe and possibly
effective drugs. If I am to continue antiviral therapy, I
must again procure a substance which is illegal and for which
very little is known. There is no excuse for this ignorance
given the long delays these drugs have experienced in the
testing process. I would have hoped that by this time at
least pilot studies would have been done on AL721, Ampligen,
Ribavirin, and Dextran sulfate to assist me in my decision.
They have not.

Based on my own experience and the experiences of other People
With AIDS, I would therefore make the following
recommendations to the Commission:

4, It is imperative that a comprehensive, up-to-date registry
of clinical studies of AIDS drugs be created in order that
patients and physicians might find appropriate clinical
studies. Locating clinical trials must not be a hit-or-miss
endeavor. A similar system, PDQ, exists for cancer trials and
must be created for AIDS trials.

 

 
 

 

e The NIH must expand clinical trials and lower the
threshold for testing potential AIDS therapies. Substances
which have passed toxicity studies and which are in widespread
use must be tested in small pilot studies to confirm or
disprove anecdotal data.

3. Community-based research groups should be given special
consideration in designing clinical trials for AIDS therapies.
These organizations represent large patient populations in all
Stages of HIV related disease who are generally eager to
participate in clinical trials. By coordinating clinical
trials with primary care, trials can be accelerated and
patients’ lives simplified.

4. Physicians and patients must be made aware of drugs which
Mave been made available through the FDA's new Treatment IND
regulations. In addition, physicians must be trained on how
to access these experimental drugs for their patients. At the
recent conference in Washington sponsored by the FDA and the
AMA, it was disconcerting that physicians left the conference
as ignorant as they arrived as to the procedure for applying
for drugs through Treatment INDs.

Thank you.

 

 
 

 

263A West 19th Street. Room 125
New York, New York 10011
(212) 627.1810

TESTIMONY OF
MICHAEL L. CALLEN
Founding Member,
People with AIDS Coalition (New York)
and
. ‘Member,
New York State AIDS Advisory Council
before
Presidential Commission on the

Human Immunodeficiency Virus Epidemic
RESEARCH HEARINGS

Friday, February 19, 1988
9:30 a.m.

My name is Michael Callen and I am a gay man with AIDS.
I was diagnosed with cryptosporidiosis in the Summer of '82
and have been hospitalized several times since then with
various opportunistic complications. I am one of the 15% or
so long term survivors of AIDS recently reported in CDC
researcher Dr. Rothenberg's long term survivor study.

I mention the fact of my long term survival to emphasize
that I've been dealing with this epidemic a long time and
I've seen a lot in the 5 1/2 years since I was diagnosed.
I've witnesse@ the desperate scramble for treatments--any

treatment. And seen friends fly around the world in search

He challenge the label “trctim” which umphes defeat.
and ue are only occasionally “patients.”

Re are people with AIDS.

 

 
 

 

of a cure, frustrated with the sluggish treatment research
response here in the U.S.

Because my time is limited, I will focus on two points.
One--and I sha'n't belabor this point--is that I do not
believe HIV has been proven, by any respectable standards of
Classic scientific inquiry--to be "the cause" of AIDS. To
that extent, I think this Commission is woefully misnamed.
But I don't intend to take up that hot potato here--at least
not directly. My point could be restated thus: the cause or
causes of AIDS remain(s) unknown and we are senselessly
limiting our search for treatments to drugs which are anti-
retroviral because we arrogantly assume that we know the
cause of AIDS.

If I understand the recent New York Times' series on
AIDS, specifically Monday, February 15th's article entitled
"Campaign to Find Drugs for Fighting AIDS Is Intensified," we
are limiting drug trials to substances which, in the test
tube, show some anti-retroviral effect. That is a lot of
eggs to be putting in the HIV basket since other viruses
which don't happen to be retroviruses may well be more
important than HIV in making people sick with what we call
AIDS. I. think a CMV treatment would do far more good than an :‘f-u
HIV treatment.

I asked FDA Commissioner Frank Young if anti-HIV
activity was the litmus test used to prioritize substances to

be tested and he denied that this was so. But the Times

 

 

 
Pi

article seems to suggest that my suspicion is correct. There
are many substances which the People with AIDS community is
clamoring for which aren't anti-retroviral, but which,
anecdotally at least, seem to be making people feel better.
Isn't this, after all, what the goal of treatment research
ought to be?

My main objection to what I call the religion of HIV is
that it oversimplifies what is a very complex disease. T-
cell problems are only one small part of AIDS. There are the
B-cell problems. And auto-immune components. Indeed, just
about everything that can go wrong with the immune system
seems to be going wrong and it seems simplistic to attribute
everything to poor HIV. I fear that by limiting our search
for treatments to anti-retrovirals, we are only pursuing one
small portion of what we might be doing.

Lipid research is a good example of this. Lipids may or
may not be anti-retroviral, but they seem to repair cell
damage--something which certainly is happening in AIDS. Why
has Dr. Fauci and the NIH only so begrudgingly begun trials?
It's as if they don't want to believe anything does damage
other than "the virus." Another example is PCP prophylaxis.
Preventing the number one killer of people with AIDS ought to
have been the #1 treatment priority. Instead, the AIDS
community has brought it about largely through word of mouth.
As a result, in nearly every AIDS practice in New York City,

PCP prophylaxis is now standard procedure--despite the lack

 

 
 

 

of the kind of "proof" that NIH seems to be demanding. And I
believe that PCP prophylaxis will, in a single stroke, save
more lives than all the AZT in the world.

Before I end with my second and final point, let me
acknowledge that I am unable to fulfill your request to
recomend “improvements in the federal agencies" or to
suggest "better working partnerships between the private
sector and Federal, state and local public entities." I am
as much at a loss as the government seems to be. Except for
the Community Research Initiative, about which you will hear
testimony tomorrow, I see no creative solutions to the log
jam of federal treatment research other than the creation of
a Manhattan project for treatments which would essentially
pursue every reasonable lead with all due haste.

That said, my final point is this. One essential fact
of human nature has been ignored in the design of federal
treatment trials, and that is that desperate people--people
who believe they are facing certain death--will lie and cheat
and generally do whatever they have to do to stay alive. In
a situation like AIDS where there are no proven treatments,
getting into a treatment trial is viewed as the only chance
one has to save one's life. In other words, we're losing the
important distinction between providing access to drugs and
the proper conduct of treatment research. They are not be

the same thing, but with AIDS they are.

 

 
 

 

Much of the treatment research done so far--and in

particular, I refer to the AZT trials--isn't very good
research because it has been designed in academic, ivory
towers, far from the real world. Placebo double-blind trials
may be the quickest, simplest and cleanest way to get good
data, but they are not the only way; and given the reality of
AIDS, it is unreasonable to expect us to participate in
placebo trials. As I said, there has been lying on the part
of participants; some doctors have fudged lab tests to permit
their patients to meet trial entry criteria; some people have
had their pills analyzed to see who was on placebo and who
was getting medication; and there's been just about every
other kind of "cheating" you could imagine.

Before you blame us, put yourself in our shoes.

Wouldn't you do the same if you believed your only hope was
to get an experimental drug?

The central problem seems to me to be the placebo
fixation of federal treatment research design. People with
AIDS should not be asked to die for the greater good of
research. Death should not be the efficacy measure of a
drug.

I will end with one suggestion which connects the two
points I've just made. There exists in the world a veritable
arsenal of substances which one could lay out on a spectrum
from herbs and lipids through highly complex and toxic

synthesized chemicals. I would suggest that one can

 

 
 

construct two parallel lines and lay out each substance along
those lines. One line would represent each substance's
toxicity--at one end, substances like lipids and herbs which
have no or low toxicity, and at the other end, substances
like AZT which have staggering toxicity. Parallel to that
toxicity spectrum would run a line along which one could
estimate efficacy--and hopefully not just efficacy as an
anti-retroviral. Rather, the question to be asked should be
this: is there any theoretical reason to believe a
particular substance will help any of the impairments found
in AIDS?

Once one has laid all substances out along these two
lines, it seems to me that the place to concentrate first is
on substances with low or no toxicity which have some
theoretical efficacy. Again, lipids provide a good example.
Instead of blasting people with AIDS with the most toxic |
stuff we've got, let's start at the other end of the
spectrum. Or, if we must, do both kinds of treatment
research simultaneously.

As others have said, and I'm sure others will say, there
ought to be many more clinical trials going on than there
are. }

The time for excuses is long past.

Thank you.

 

 
 

Testimony of Jay C. Lipner

My name is Jay C. Lipner. I am an attorney here in New York City.
I am a partner in the law firm of Silverstein, Langer, Lipner &
Newburgh. I volunteer my time to Lambda Legal Defense and Education
Fund, the Community Research Initiative, and Gay Mens Health Crisis.
(GMHC)

I am a member of the Subcommittee on Access to Therapeutic Trials
of the New York State Department of Health AIDS Advisory Council. My
legal background includes ten years of experience with federal/state
income assistance programs, which familiarize me with federal
litigation, rulemaking, and legislative analysis. I have also had three
years of experience with toxic waste litigation, which involved daily
and close work with the New York State Department of Health. I have
worked in both New York and Washington, D.C.

I have been involved with AIDS as an attorney since 1982, when I
first began to work with GMHC. I have had scores of clients with AIDS.
I have visited them in hospitals when they were too ill to come to my
office. I have seen people get sick and die, and have watched in
growing frustration as the epidemic has grown. After five years of day-
to-day exposure to AIDS, I thought I understood what it was like, but I
was wrong. I did not gain that insight until I also became a person
with AIDS.

I got sick with very little warning in March, 1987, when I
developed pneumocystis carinii pneumonia (PCP). While recovering, I
decided not to return to private practice. It is too stressful, and
makes time and deadline commitments I no longer felt capable of meeting..,
I decided instead to volunteer my time as a lawyer to Lambda Legal

1

 

 
 

 

Defense on the issue of access to experimental drugs. I did this for
two reasons: first, to utilize my skills and knowledge as a lawyer at a
pace that I could manage; and second,. to keep on top of drugs and

treatments which might prove beneficial for myself.

4 .
an

My first lesson in drug education came soon. After I had recovered
from PCP, my doctor strongly recommended that I begin taking AZT. I
knew that AZT had possible toxic side effects, and was very anxious
about starting it, but it did not seem that I had any viable options.
As my knowledge grew, my concerns multiplied. I began to understand how
the FDA's policy has limited the availability of drugs for people with
AIDS and ARC. This is what I want to talk about today. I am testifying
both as a person who has sought drugs for treatment use and as an
attorney on behalf of Lambda Legal Defense. Lambda is the ‘nation's
oldest and largest lesbian and gay legal organization, and in recent
years has been in the forefront of the nationwide fight against AIDS-

based discrimination.

AZT is an anti-retroviral drug. It works by preventing replication
of the HIV-virus. It does not help reconstitute an already crippled
immune system. To accomplish this, one needs an immunomodulator. To
date, however, no immunomodulator has been approved by the FDA for use
in treating AIDS. The FDA has approved only AZT. And as time went by,
I began to understand ;how the FDA's policy has limited the availability

of drugs for people with AIDS and ARC.

rs

 

 
 

As the Commission members know, before a drug may be _ sold

commercially for a new treatment use, the manufacturer must obtain
approval from the FDA. It does not matter if the drug is approved for
use in other countries, or has been approved for a different treatment
use. Each new or different treatment use must be approved by the FDA.
This process is lengthy and complicated, and moves by stages through
initial research, data on animal toxicity, and human trials, which
progress in stages (Phase I to Phase II to Phase III). At any step
along the way, the FDA may reject data without giving its reasons.
Similarly, the FDA may also refuse to approve commercial marketing of

the drug when trials are completed, again without giving reasons.

Drug approval is a risky and expensive game which can take 5 to 7
years or longer. The process heavily favors the NIH and large drug
companies, which have the staff, the experience, and the budget to play
the game by the FDA's rules. In the interim, until a drug has been
approved for use, (or granted “orphan drug" status) there are only two
ways for a patient to lawfully get drugs in this country: (a):
participating in a drug trial or (b): asking for the drug on a
"compassionate need" basis. Both these approaches had _ serious
drawbacks. Drug trials are limited in their size and location, and have
rigid inclusion and exclusion criteria. Compassionate use is viewed as
a last ditch effort, and is used on a case-by-case basis for patients
who are critically ill. It involves considerable paperwork on the part
of the treating physician. What other options are open to people who

have already developed AIDS? This is the question I started with.

 

 
 

 

Within a short period of time, I thought I had an answer -- a "treatment

IND".

Treatment IND is the name FDA has given to a new policy set forth
in regulations issued on June 22, 1987, in the Federal Register. These.
regulations purport to make experimental drugs more widely available to

people with AIDS, and has been widely reported in the press.

The treatment IND regulations are not easy to understand because
they are poorly written and raise more questions than they answer.
These are the essentials: a drug company may apply to the FDA to sell a
drug for treatment use even while that drug is still undergoing clinical
trials. The manufacturer must be actively pursuing approval of the
drug, and the drug must be intended for use in a life-threatening or
serious illness. Life-threatening is defined in the regulations as
including AIDS. A treatment IND may be granted for persons with AIDS as
early as Phase II of clinical trials. A drug may be approved for
persons with a serious illness once the drug has reached Phase III.
Since the regulations do not define serious illness, it is not clear how

a person with ARC would be treated.

Although the regulations stress that a treatment IND is to be used
for drugs which have manageable or acceptable side effects, there is no
standard for judging whether a drug has proved sufficiently effective to
warrant treatment use prior to final approval. This is left solely and

completely to the F.D.A. Commissioner.

 

 
 

Since the application must be initiated by the drug company, with
no indication of the standard for approval, why would companies want to
apply for a treatment IND? The answer is they wouldn't. It is not in
their interest. It is not in their interest for several reasons: (a),
the treatment IND would invite unwelcome scrutiny of interim pricing of
the drug; the drug company loses control over the collection of data
when the drug is taken outside the scope of a clinical trial, thus
possibly jeopardizing their NDA; (b), a treatment IND would increase the
number of persons receiving the drug, thus increasing the drug company's
potential liability if someone gets sick while taking the drug; and (c),
the application process would impose additional requirements of staff
time, paperwork, and product procurement. For these reasons, and
others, a treatment IND would be counterproductive, and might jeopardize
ultimate approval of the drug. The fact that only government-sponsored
drugs have been granted treatment IND status illustrates this problen.
The large pharmaceuticals will not apply. Trimetrexate is an NIH
sponsored drug. The interim of approval of AZT came before the
treatment IND regulations, not as a result. It is thus not surprising,

that eight months after FDA issued the regulations, little has changed.

Please let me give you a personal example of how FDA policy affects
people with AIDS. I asked my doctor to try to obtain a drug called
Imuthiol for my use as an immunomodulator. The drug is manufactured in
France, and is being used there in the treatment of AIDS. The drug is

in FDA-approved clinical trials in only six locations in this country,

 

 
 

 

none of which is in New York State. My doctor wrote to the manufacturer

and requested that this drug be made available to me on a compassionate
use basis. The company declined, citing its desire to complete the.
formal FDA approval process before making the drug further available.
Other doctors also approached the company, but to no avail. At that
point I helped to draft a letter to the company from Lambda Legal
Defense and others requesting that the company institute a treatment IND

for this Imuthiol. The company has not yet replied.

These efforts to obtain Imuthiol took months, and produced nothing.
I am no closer than when I started. If I wish to obtain the drug, my
only option at this point is to go to France and attempt to obtain the
drug there. This would be difficult for several reasons. My only
income is from Social Security and a private disability policy. A trip
to France would be prohibitively expensive, depleting a month's income.
I fear the trip would subject me to considerable physical stress, which
I doubt would do anything to improve my health. Obtaining the drug in
the United States is also out of the question. The clinical trials are
closed. Even if they were open, I could hardly afford to commute to

Texas, California or Arizona.

My dilemma, I believe, illustrates clearly how lack of access to
drugs affects people with AIDS. AZT has proved too toxic for me to take
at full dose. Even at half dose, I have required two transfusions. If

I must take AZT, I want access to other drugs that will help repair my

immune system. If time permitted, I could give you other examples of

 

 
 

 

drugs that might prove beneficial to me now or at a future time, but I
hope this illustrates the point. This effort to obtain drugs is time
consuming, stressful, and mentally exhausting, and I suspect that being
a lawyer equips me better than most people with AIDS to deal with the
issue, &fter several months of research on treatment INDs, I have
concluded the FDA never intended the treatment IND process to work in
any significant way beyond AZT. It was intended to obtain favorable
press for the FDA, and in that, it worked. The conflict between the
reality of the drug regulation process and the treatment IND regulations
has wholly escaped television, radio, and the print media. Commissioner
Young has made frequent statements to the effect that the treatment IND
regulations mark a major change in policy, and the press has duly
reported it. But there has been no major change in policy. What there
has been instead is an effort by the FDA and the Reagan administration
to create the impression that drugs have somehow become more available
to people with AIDS. In the interim, the death toll from AIDS mounts

daily.

If the FDA is truly interested in making drugs available to people
with AIDS and ARC, it must restructure the treatment IND regulations.
The FDA should begin by removing the emphasis on a drug's effectiveness.
Efficacy is the standard to be used for final approval. If the same
standard is used for a treatment IND, the regulation is meaningless.
The appropriate question for the FDA should be whether the drug has
Manageable side effects. If the answer is yes, then persons with AIDS

and ARC should have access to the drug while the clinical trials

 

 
 

 

proceed. The FDA's present policy does the opposite. It denies access
to people who are dying because it is not clear the drug will work.
This is absurd. The FDA's policy also fails to address the concerns of
the drug manufacturers. Drug companies should be given financial
incentives to encourage them to apply for a treatment IND similar to
that given to orphan drugs. In addition, the FDA must provide
assurances that application for and subsequent use of a treatment IND
will not jeopardize final approval. Another means of providing
incentives to pharmaceuticals to apply for treatment IND would be for
the FDA to promise to give priority to those NDA's in which a treatment
IND has been submitted. If these steps require changes in the FDA

statutory authority, such changes should be undertaken immediately.

I hope the Commission understands my frustration in being allowed
only five minutes to address such a complex issue, while Frank Young has
two hours. I would therefore like to emphasize that while doing
research on this issue, I have spoken and met with many, many people
knowledgeable about the FDA process, including Commissioner Young. My
consistent impression is that the FDA is in disarray, does not have
clear policy on treatment IND's, and has placed its greatest emphasis on
public relations. I believe such a conclusion is inescapable, for as we
sit here discussing this issue, the situation remains as it was on May

22, 1987 when the regulations were issued.

 

 
 

I appreciate the opportunity to testify, and would welcome any

questions members of the Commission may have.

Jay C. Lipner
February 19, 1988
New York, New York

Silverstein, Langer, Lipner & Newburgh
95 Madison Avenue
New York, NY 10016

 

 
 

 

STATEMENT OF

FRANK E. YOUNG, M.D., Ph.D.

COMMISSIONER OF FOOD AND DRUGS

FOOD AND DRUG ADMINISTRATION

U.S. PUBLIC HEALTH SERVICE

DEPARTMENT OF HEALTH AND HUMAN SERVICES

BEFORE

PRESIDENTIAL COMMISSION ON THE HUMAN
IMMUNODEFICIENCY VIRUS EPIDEMIC

NEW YORK, NEW YORK

FEBRUARY 19, 1988

 

 
 

I am pleased to be here today to participate in the Commission's
hearings on the development of new drugs and vaccines to treat
and prevent the spread of AIDS. The Food and Drug
Administration has an important role in the war against AIDS, and
I am happy to describe that role for you today. I want you to -
know that we are committed to this battle, will modify our
procedures to contribute in any way possible to win this war,
while still assuring safety and effectiveness, and will divert

whatever resources are necessary to ensure our responsiveness.

My testimony will focus on four main subjects today--how FDA
regulates drugs, vaccines, blood products, and medical devices;
the procedures we have put into effect to expedite the review of
AIDS therapies and diagnostics; our accomplishments thus far in
managing challenges posed by the AIDS epidemic; and our view of
FDA's future role in assisting in the war on this terrible

affliction.

I believe it significant that we at FDA have instituted new
procedures for reviewing AIDS drugs, so that they are our highest
priority, and new procedures for making investigational drugs
more widely available to the desperately ill; reorganized our
drug and biological review offices to better concentrate our
efforts on those therapies; approved the first anti-AIDS drug,
zidovudine, in record time, and human testing of the first two

AIDS vaccines as well; and stepped up our efforts to ensure the

 

 

 
 

 

3
safety of medical devices, such as condoms and gloves, that

protect against AIDS.

Nevertheless, it is equally significant that the challenges ahead
that are posed by AIDS are tremendous. FDA is a crucial link in
efforts to transfer AIDS research into therapy for patients.

That research is growing at such a rapid pace that we are
challenged to ensure that we have sufficient capability to
oversee the testing of new AIDS therapies and the eventual

approval of those that prove effective.

I want to expand upon those accomplishments and those challenges
for the future. But first, let me note that AIDS is clearly too
big an issue for any one Agency of government to handle, and that
the Department of Health and Human Services, through the Public
Health Service, has done a remarkable job of coordinating and
supporting the efforts of its constituent agencies in their
fight against AIDS. Indeed, I cannot overemphasize the
importance of the efforts made by Secretary Bowen and Assistant
Secretary for Health Windom in leading that fight. That
coordination is assured by the work of the PHS Executive Task
Force on AIDS, which is chaired by Dr. Windom, and to which FDA
reports on every significant AIDS activity undertaken by me and
my staff. Indeed, we rely on Dr. Bowen's and Dr. Windom's

leadership on virtually a daily basis.

 

 
 

 

4

FDA'S RESPONSIBILITIES AND ORGANIZATION

As you know, the Food and Drug Administration's role in
combatting AIDS is based primarily in its responsibility for the
premarket review of new drugs, biologicals, and medical devices.
To ensure that those products, once developed, reach AIDS
patients as rapidly as possible, FDA has given the highest
priority to providing the most timely and efficient premarketing

review possible of promising new AIDS therapies.

To assure that AIDS products get that highest priority, we have
implemented a number of management initiatives. First, last
fall we divided FDA's Center for Drugs and Biologics into two
new centers--the Center for Drug Evaluation and Research--or
CDER--and the Center for Biologics Evaluation and Research. As
the attached organizational chart shows, CDER is responsible for
the review of most new AIDS drugs. Within CDER, the Center's
Director, Dr. Carl Peck, created this month a new Division of
Anti-Viral Drugs that can concentrate on reviewing the new

therapies being developed to combat the HIV virus.

To complement our review of new drugs, our Center for Biologics
Evaluation and Research, or CBER, is responsible for the review
of new vaccines, blood products, AIDS diagnostic kits, and
biological drugs (primarily the immunomodulators designed to

strengthen the body's immune system). To better manage the boom

 

 
fT

5
in new AIDS biologicals expected to result from developments in
biotechnology, CBER's Director, Dr. Paul Parkman, is planning
the creation of a new Division of Cytokine Biology, which will
contain several laboratories capable of in-depth study of cell
biology, immunology and other possible keys to understanding this
deadly virus. I have also consolidated the coordination of all
of FDA's AIDS-related activities under Dr. Parkman's able
leadership, to ensure that issués dealing with AIDS are properly

coordinated throughout the Agency.

FDA'S DRUG REVIEW PROCESS

Let me now summarize for you how the premarket review process
operates and then discuss how we have modified our procedures to
help people who are desperately ill with AIDS. Before clinical
testing can begin for an experimental drug or vaccine, the
sponsor or investigator must file an investigational new drug
application, or "IND," with FDA. The IND must demonstrate, based
on animal studies, that it is reasonably safe to test the drug on
human subjects. This process is normally accomplished in 30 days
with 95% of IND application; but for AIDS drugs we aim for just 5

days.

After FDA completes the IND review, the sponsor assumes the
responsibility for the development of the drug. Clinical
testing, whether done by the pharmaceutical company, an academic

institution, or the National Institutes of Health, is normally

 

 
 

6
divided into three sequential phases. As the attached chart on
the drug approval process illustrates, Phase 1 is the initial
introduction of an investigational therapy into humans to
determine safety... Phase 1 studies are designed to explore
pharmacologic actions of the therapy, how the body breaks the
drug down, and the side effects associated with varying doses.
Phase 1 usually includes less than 100 patients, usually healthy

ones, and may take a year to complete.

The second phase is the first controlled clinical study to
evaluate the effectiveness of the drug for a particular
indication and to determine common short-term side effects. A
phase 2 study typically involves a few hundred patients. Most of
the drugs that will fail do so in Phase 1 and 2. In fact, 90% of
the drugs that are abandoned during IND research do so during

Phases 1 or 2.

Once a phase 2 study is completed, the drug's sponsor has learned
much about the drug's safety and effectiveness, and a larger
controlled study using several thousand patients~--phase 3--can be
conducted. This large study can collect enough information to

prove that a drug really works and can be safely marketed.

Once phase 3 testing is completed, the sponsor submits the test
results to FDA in the form of a new drug application or biologic

license application. FDA's medical officers, chemists,

 

 
 

 

7
statisticians, and pharmacologists review the application to
determine if the sponsor's data in fact shows that the drug is
safe and effective. Therefore, of the eight years that are
typically devoted to the clinical study of drugs by the sponsor,

about two years are required to review the drug.

To make this process more efficient, FDA has recently completed
an extensive reform of the regulations governing the drug review
process. The new regulations are intended to simplify and
expedite the testing and application review phases of new drug
development. Concomitant with those new regulations have been
guidelines to help sponsors better plan their clinical testing:
and to encourage careful planning between FDA and sponsors--to

ensure that testing will fully meet FDA's needs for safety and

efficacy data.

Finally, we also recognize that there are times when a new
experimental drug holds the promise of hope for desperately ill
patients--such as AIDS patients. In those cases, it seems
imperative that we allow desperately ill patients access to those
drugs once a reasonable body of data exists. Although FDA has
for years permitted some patients access to such drugs, last year
we reached the conclusion that a formal provision should be
written into FDA's regulations permitting expanded use of
experimental drugs. These so-called "treatment INDs" will allow

broader use during the second phase of clinical testing of drugs

 

 
 

 

8
for immediately life-threatening diseases. We developed criteria
for determining whether a treatment IND is appropriate for

particular drugs:

1) That the drug is intended to treat a serious or

immediately life-threatening disease;

2) There is no comparable or satisfactory alternative or
other therapy to treat that stage of the disease in the

intended population;

3) The drug is under investigation in a controlled clinical
trial under an IND in effect for the trial, or all clinical

trials have been completed; and

4) The sponsor for the controlled clinical trial is actively

pursuing marketing approval of the investigational drug.

For drugs intended to treat an immediately life-threatening
disease, a request may be denied for treatment use if the
available scientific evidence, taken as a whole, fails to provide
a reasonable basis for concluding that the drug (1) may be
effective for its intended use in its intended patient
population, or (2) would not expose patients who receive the drug

to an unreasonable and significant additional risk of illness or

injury.

 

 
 

 

9
The drug AZT served as the model for these new regulations, when
over 4,000 patients received the drug prior to formal marketing
approval. And just last week we approved the drug Trimetrexate
as a treatment for AIDS patients with Pneumocystis Carinii
Pneumonia who cannot take approved therapies because of serious
adverse reactions. We promise to bring breakthrough drugs to
desperately ill patients as rapidly as possible. As you know, I
have committed myself, not only to the development, but to the
implementation of this process. Since the regulation was
written, we have approved 3 drugs for Treatment INDs--.
Trimetrexate; Cytomegalovirus Immune Globulin for infections in
renal transplant patients; and Ifosfamide and Mesna for a form of
cancer. Additionally, we have fostered the administration of the
drug ganciclovir--for CMV Retinitis-- to 1500 AIDS patients on a

"compassionate IND" basis.

FDA'S PROGRESS TO DATE
Our efforts have already begun to produce real progress in
assuring that FDA does its part in fighting AIDS. Let me

summarize some of the accomplishments made thus far.

Drug Review
° A special classification, known as "1-AA," has been
established for all AIDS drugs, to ensure that they receive

the absolute highest priority in the drug review process.

 

 
 

 

10
The first new drug application for AIDS--for zidovudine
(formerly known as AZT)--received FDA approval in record
time (3 1/2 months). This timeliness stands in sharp
contrast to the 2 years or more the average new chemical
entity spends in the review process. However, to accomplish
such an expeditious review, FDA staff expended 8 manyears of
effort, at a cost of $600,000, to review a new drug

application 20 linear feet-tall.

FDA has received 179 applications for approval to test 120
new AIDS drugs, diagnostics and vaccines, and has approved
90% (154) of those applications thus far. The approved

applications for human testing include:

- 35 for anti-viral drugs - 45 for immunomodulators
- 4 for anti-neoplastics - 31 for drugs for
- 36 for diagnostics opportunistic infections

3 for AIDS vaccines

Furthermore, the number of these applications has been

increasing markedly, as shown by the attached chart.

It's important to point out, however, that 95% of those
investigations are still in Phases I and II of clinical
testing, and we know little of their true safety and

efficacy.

 

 
 

 

11

° We are fortunate in having about a dozen anti-infective
drugs that have already been approved by FDA, and that are
proving useful against opportunistic infections in AIDS
patients. Their presence has given physicians a small but

important armamentarium against the ravages of the disease.

° Under the authority of the Orphan Drug Act, we have
designated AIDS therapies as eligible for tax incentives and
grants for products of limited commercial value. Thus far,
7 drugs for the treatment of AIDS, 3 for Kaposi's Sarcoma,
and 4 for Pneumocystis Carinii Pneumonia have received
"orphan" designation. Four grants for research on orphan

drugs to treat AIDS have also been made.

Vaccines |

On August 18, FDA granted permission for the first clinical study
in humans of an experimental AIDS vaccine. That was an important
first step in the development of a vaccine to prevent infection
by the AIDS virus. The vaccine, manufactured by MicroGeneSys,
Inc. of West Haven, Connecticut, consists of purified protein
from the genetic material of the HIV virus, and was developed
using recombinant DNA techniques similar to those employed in the

manufacture of other recombinant vaccines. We approved a

 
 

Po

12
clinical trial for a second AIDS vaccine in November. This
vaccine, produced by Bristol-Myers Company of New York City, is
made from vaccinia virus into which genes from the surface
proteins from the AIDS virus have been inserted by recombinant
DNA techniques. And most recently, we have granted an IND to the
National Institutes of Health for NIH testing of the Bristol-

Myers vaccine.

The Blood Supply

The initial screening test--the ELISA--was first licensed by FDA
for commercial use in 1985, to ensure that the nation's blood
supply is a safe one. In fact, the first three ELISA tests to be
licensed were the result of extremely rapid concurrent review by
FDA's biologics specialists--3 months or less--despite the
complexity of the clinical trial data used to support the
licensing applications. In all, we have approved 7 ELISA tests.
In April 1987, FDA licensed the first Western Blot AIDS test kit
for commercial use in validating initial positive screening tests

for antibodies to the AIDS virus.

We believe use of the Western Blot method, in conjunction with
the ELISA test, could help potential blood donors who have
falsely tested positive by the ELISA method to be reentered into
the blood donor pool. The two tests together have gone a long

way toward assuring the nation that the blood supply is a safe

 

 

 

 
 

 

13

one.

FDA also has several new blood screening products under expedited
review, either for marketing approval or for approval of human

testing. Those include:

oO ELISA tests designed to detect presence of the AIDS virus

itself in blood;
oO Screening ELISA tests using recombinant DNA technology;

oO Detection tests for antibodies to other viruses similar to

HIV (e.g., HTLV-1, HIV-2);
oO Rapid immunoassays; and

° Blood sample collection kits for use by physicians for HIV

antibody detection.

Semen Banks

We have also made just this month, in conjunction with the
Centers for Disease Control, recommendations on semen banking and
organ and tissue transplantation. Those recommendations have
been provided to you for the record. They provide for the HIV

testing of semen and organ and tissue transplant.

 

 
 

 

14

Medical Devices

FDA regulates four types of AIDS-related medical devices--barrier
products, such as condoms and rubber gloves; commonly used:
clinical devices that could transmit HIV if not handled properly,
such as dental drills and bronchoscope; modified clinical

devices designed to minimize risk of transmission, such as
"stick-proof" needles; and devices to treat AIDS, such as

biostimulation devices.

For condoms, our primary goal has been to assure adequate quality
of the products. We have increased our inspection of
manufacturers and processors, and developed a program for testing
both domestic and foreign-made condoms to ensure conformance with
FDA's criteria for acceptability. If condoms are found out of
compliance with our criteria, they are removed from the market.
Because of these programs, we are observing increased quality
control by manufacturers, and a concomitant reduction in the
number of faulty condomsleaving the factory. Our program for
ensuring the quality of rubber surgical and examination gloves is
also underway and involves an acceptable criteria for glove
quality. Although there is no evidence at this time that glove
failure has ever contributed to a case of HIV infection, we are
determined to ensure that gloves meet the highest possible
standard for protecting health care workers from exposure to

infection.

 

 
 

 

~

For devices that could transmit the AIDS virus, we are surveying

the methods of disinfection to learn how sterilization procedures
may be improved, and we are working with device manufacturers to.
improve device design in ways that would minimize risk. The
development of devices intended specifically to minimize the risk
of AIDS transmission, such as "stick-proof" needles, could be a
substantial benefit to health cate workers. We will be
monitoring such devices to ensure that they actually do reduce
transmission risk. Only one device has yet been submitted to FDA
for approval of human testing as an actual treatment for AIDS-~-an
electro-magnetic field generator device for treating AIDS-Related
Complex. Results of that testing are not yet in, but we intend

to. give all such devices the most expeditious review possible.

Research

FDA staff are actively involved in AIDS research in several
areas, much of it in coordination with our colleagues at the
National Institutes of Health, who have the lead responsibility
for AIDS research. It should be emphasized that our research is
much different from that at NIH. FDA focuses on research that
will facilitate our regulatory actions. Among our research are
comparative analyses of diagnostic tests, methods to validate
vaccine safety, studies of the basic immunologic defects

associated with the disease, examinations of the biological and

 

 
 

 

16

chemical properties of natural interferons and their ability to
modify the immune system, and efforts to develop in primates an
animal model for AIDS research. We are also funding private AIDS
research on the safety and efficacy of AIDS vaccines, on testing
for HIV antibodies in blood donors, and other AIDS-related
research. And finally, the Center for Drug Evaluation and
Research is preparing a major new research effort focusing on

optimizing dosages of AIDS drugs as they are developed.
Fraudulent Products

We have recently seen an increase in the number of fraudulent
products intended for AIDS patients and those who fear coming
down with the disease. So-called "treatments" include blue-green
algae, injections of hydrogen peroxide, the food preservative
BHT, pills derived from mice that have been given the AIDS virus,
and herbal capsules that contain poisonous metals. For
uninfected consumers, there are products such as a spermicide
that untruthfully claims to kill the AIDS virus and the "Sani-
Form," a piece of plastic to cover telephone mouthpieces that was
promoted to protect against infection from public phones. The
latter, of course, not only takes people's money, but erroneously
promotes the idea that AIDS can be contracted by touching items

handled by someone infected with HIV.

To counter these forms of fraud, we have mobilized our field

 

 
17
inspectional force to investigate those promoting fraudulent
claims, prepared numerous major articles for health care
publications, and initiated a public information program to
alert AIDS patients and consumers against these fraudulent

products.

Public Education and Information

 

Another part of our public education effort is aimed at improving
the knowledge citizens have about AIDS and ways to combat the
disease. For example, we have issued special publications of our
FDA Drug Bulletin to physicians, distributed instructions on the
proper use of condoms and surgical gloves, developed an award-
winning information package for the medical community, and we
publish a monthly. update on AIDS drugs that are under development

and review.

We have also stepped up our educational efforts aimed at helping
people understand why there aren't more AIDS therapies being
approved by FDA. You may know that some citizens, even AIDS
patients, claim that there are effective AIDS drugs in existence,
but unavailable because FDA will not permit their marketing.

This is just not true. Thus, we are trying to improve public
understanding of the drug approval process. I have brought with
me copies of our recent publication on the drug development

process, which is intended to help consumers understand that

 

 
18
drug development often takes eight or more years, yet FDA's
review time occupies only a relatively small fraction of that
time. We intend to ensure that our review time for AIDS drugs
will take no longer than 180 days; AZT, as I mentioned earlier,
was approved in 107 days. In fact, AZT's was the fastest review
in recent times. And we must see to it that people understand
that there is no backlog of AIDS drugs awaiting FDA review.
Indeed, there is not one single new drug application for the
treatment of the AIDS virus itself pending in the Agency today.
Therefore, is important to emphasize that much of the frustration
today is due to the difficulty in developing good AIDS drugs, and
the length of time required to obtain an evaluation of candidates
by sponsors (rather than delay by FDA). Furthermore, it is also
important to state clearly that, if the past is a prologue to the
future, 80% of the drugs now under investigation will fail to be

safe and effective.

THE FUTURE

The task ahead for the public and private organizations trying to
develop AIDS therapies is enormous. Indeed, finding effective
drugs against any viral illness is extraordinarily difficult.

One statistic illustrates that fact powerfully: to date,
hundreds of antibacterial agents have been discovered, to cure
virtually any bacterial infection; yet in all our years of

experimentation, only seven antiviral agents ever reached the

 

 
 

19

stage where safety and efficacy are known.

Fortunately, the public and private research on AIDS drugs that
has been underway since the early 1980s has begun to bear fruit.’
As I mentioned earlier, FDA has approved 115 applications for
human testing of 81 AIDS and AIDS-related drugs, including 21
antiviral agents and 39 immunomodulators. As the attached graphs
demonstrate, NIH research is growing in response to the AIDS
epidemic, at a rate approximately equal to private research,
which should cause a continued exponential growth in the number
of Investigational New Drug applications for AIDS therapies.

As research increases for finding a treatment for AIDS, FDA's
funding for product review must increase concurrently, so that we
never become a bottleneck to the successful development of AIDS
treatments. Indeed, I believe FDA should be a bridge between the
scientists who do the research and the patients who need the
products of that research. I commend Drs. Wyngaarden, Fauci,
Broder, and others at NIH for their vigorous efforts to develop
this research program, as well as the many other scientists
within and outside government who are devoting such dedicated

effort to finding a cure for AIDS. But we cannot be complacent.

There is no cure for AIDS today.

Fortunately, we at FDA’ know something about building bridges.

And over the years we have evolved five key elements for assuring

 

 
 

 

20

the expeditious transfer of new drug development to patients.

The first is the all-important initial communication with the
sponsor. FDA staff, sometimes including myself, meet with new
drug and vaccine sponsors to help them design their clinical

trials.

Second, we continue that communication during Phase II and III
testing, to protect against false starts and to assure that our
expertise in designing clinical trials is provided to sponsors.
This is particularly true of research being conducted’by our
colleagues at NIH, and in many small companies that have not

traditionally been involved in drug development of this sort.

Third, we must--and do--always remember the crucial element of
public confidence. Americans must know that the drugs and
vaccines they use have been given the rigorous "stamp of
approval" of FDA's scientists--that they can be confident that

their therapies do work and are effective.

Fourth, we developed a way of getting a good product over that
bridge before the span is fully completed. I'm referring to the
Treatment IND regulation I mentioned earlier. With Treatment
INDs, we can permit the use of promising experimental drugs for
the desperately ill while clinical trials are being completed--as

we did with AZT and are now doing with Trimetrexate.

 

 
 

On

21

Finally, FDA must have enough workers to build that bridge. As
public and private AIDS research increases, demands will flow to
FDA from drug developers for guidance in designing research
protocols and for final product review. When that happens, as it
surely will--and already is--FDA must be a catalyst and
facilitator, not a rate-limiting factor slowing the movement of

products across my theoretical bridge.

Although we readily devoted 8 manyears of effort over a 3 1/2
month period to the review of AZT, as I described earlier, our
ability to "drop everything" to review new AIDS drugs is limited.
In fact, if only the percentage of INDs that normally become
applications for marketing--20%--reach that stage, we would be
hard pressed, because of the overwhelming workload, to swiftly
transfer the fruits of the research efforts, as we did with AZT,

to the patients who so desperately need then.

We are working with Drs. Bowen and Windom within the Department
of Health and Human Services to secure the necessary resources to
prepare ourselves for the expected future demands for review of
AIDS therapies. And we are reallocating resources within FDA as

well, with the understanding that no more important priority

 

exists than the war against AIDS. Finally, we are working
closely with the Institute of Medicine and the Pharmaceutical

Manufacturers Association to develop creative new solutions to
Pi

22
our substantial manpower recruitment and retention problems--
solutions such as fellowship and physician training programs,
improved automation, and assistance from academia. I welcome
your suggestions for improvements in these areas as well. We

stand prepared to implement your good suggestions.

Thank you.

 

 
 

 

FDA COORDINATION OF AIDS ISSUES

 

COMMISSIONER -. FRANK E. YOUNG, M.D., PH.D.
DEPUTY COMMISSIONER - JOHN A. NORRIS, J.D., M.B.A.

 

 

 

 

 

|

 

CENTER FOR DRUG
EVALUATION AND
RESEARCH

(CARL PECK, M.D.)
DIRECTOR

 

 

 

DRUG REVIEW

- ANTI-VIRALS

- IMMUNOMODULATORS

- OPPORTUNISTIC
INFECTIONS

- ANT!I-NEOPLASTICS

-

AIDS COORDINATOR
----- (PAUL PARKMAN, M.D.) |- - - -— —

 

 

 

 

 

CENTER FOR BIOLOGICS
EVALUATION AND
RESEARCH

(PAUL PARKMAN, M.D.)
DIRECTOR

 

 

 

- BLOOD SAFETY AND TEST KITS
- VACCINES

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- RESEARCH

|

 

 

ADDITIONAL
RESPONSIBILITIES
MEDICAL DEVICES

FIELD FORCE / INSPECTION
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Approved As of Jan. 31, 1988

 

 
 
 
 

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Pharmaceutical
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GERALD J. MOSSINGHOFF
PRESIDENT, PHARMACEUTIAL MANUFACTURERS ASSOCIATION

BEFORE THE

PRESIDENT'S: COMMISSION ON
HUMAN IMMUNE VIRUS EPIDEMIC

NEW YORK CITY, NEW YORK
FEBRUARY 19, 1988

Mc. Chairman and Members of the Commission:

I am Gerald J. Mossinghoff, President of the Pharmaceutical
Manufacturers Association. PMA represents more than 100
research-based pharmaceutical companies that discover, develop
and produce most of the prescription drugs used in the United
States. I appreciate very much this opportunity to appear before
the Commission to discuss our industry's intensive efforts to
develop drugs to combat Acquired Immune Deficiency Syndrome

(AIDS).

I will begin by providing a brief overview of the research-
based pharmaceutical industry. Thereafter, Dr. Patrick Gage,
Vice President and Director of Exploratory Research at Hoffmann-
La Roche Inc., will discuss the challenges of viral research and

federal/private cooperation; Dr. David W. Barry, Vice President

1100 Fifteenth Street, N.W. Washington, D.C.20005 (202) 835-3400
a a DS

 

 
 

 

of Research at Burroughs Wellcome Co., will describe his
company's experience in developing Retrovir (AZT), and Dr. George
B. Rathmann, President and Chief Executive Officer of AMGEN, will
concentrate on the role of biotechnology in the battle against

AIDS.

Our companies recognize the urgency of discovering and
developing drugs to stem the AIDS epidemic--one of the most
serious public-health problems this country has ever faced.
Never before have so many companies devoted so many resources in
such a short period of time to combat a single disease. Fifty-
five companies are developing, or have developed, a total of 77
products to diagnose, prevent or treat AIDS. This is shown in
Appendix A of my statement, which is reproduced in the charts on

display here today.

Despite this impressive range of activity, no one should
under-estimate the enormous challenge of discovering and
developing products to combat AIDS. According to our best
scientists working in this area, there is insufficient basic
scientific knowledge about viral diseases generally, and
specifically about the HIV virus and its effects on the body,
particularly the immune system. For more than three decades,
scientists have been trying to develop drugs to treat viral
diseases and only a handful of products with limited application

have been produced.

 

 
 

 

In the relatively brief time since AIDS was recognized as a

public-health threat, private companies have developed nine

‘ diagnostic tests, including screening tests to ensure the safety
of the nation's blood supply, Retrovir to arrest the development
of the disease and Pentam 300 to treat PCP. Just this week, the
Food and Drug Administration, by granting a Treatment IND,

approved the expanded use of another drug to treat PCP.

Contrary to what many people believe, our companies use
their own funds to discover and develop new drugs. The
government provides less than one-tenth of 1 percent of all the
funds our companies use for this purpose. Last year, our
companies invested a record $5.4 billion on’ research and
development in all disease categories. This year, they will
spend almost as much on all of their pharmaceutical research and
development as the National Institutes of Health will spend on
all biomedical research. (A more complete discussion of our
industry's investment in research and development in all areas is

provided in Appendix B of this statement. )

As a result of this enormous investment in research and
development, private pharmaceutical companies discover most, and
develop all, of the new drugs that are introduced on the U.S.
Market. In working to combat AIDS, each company is concentrating
efforts in the areas it believes will be most fruitful based on

od te: he

148
its previous research and existing sc entific capabilities. As I

have noted, 55 companies are developing, or have developed, a

 

 
 

 

total of 77 products to diagnose, prevent or treat AIDS. The
products now being developed include 15 antivirals, 22
immunomodulators (to strengthen the immune system), two anti-

infectives, 17 diagnostics and 10 vaccines.

All of the products are listed in Appendix A, which is based
on a detailed survey conducted by PMA. This Appendix specifies
the manufacturer of each product, the proposed use of the product
and the product's development status. Appendix A also describes
the various phases of the drug-approval process the FDA uses to
approve new drugs as safe and effective. Of course, not all of
the products described in the Appendix will prove to be safe and
effective. A number of them, therefore, will not be developed as
testing proceeds, but other products will be discovered and

developed as research continues.

To conquer AIDS, government, industry and academic
scientists have worked well together, but the time has come to
provide a-more effective arrangement to accelerate the
development of new therapies. The National Institutes of Health
established a network of AIDS Testing and Evaluation Units
(ATEUS) to facilitate the development of AIDS drugs. In creating
the ATEUs, the NIH recognized that there was a finite number of
AIDS patients suitable for clinical trials under FDA criteria,
and a limited number of qualified clinical investigators and
appropriate clinical facilities. The ATEUs have been useful,

but, with the increasing number of AIDS drugs to be tested, it is

 

 
 

 

wag
, {

time to re-examine their role and administration.

To discuss this and other issues that inevitably will arise
as AIDS-related research and development continues, there is a
need for a forum where government, academia and industry can meet
to assess progress in the battle against AIDS, resolve problems
as they emerge and thoroughly discuss all relevant issues. The
National Academy of Sciences' Institute of Medicine is uniquely .
qualified to provide such a forum. It is highly respected by the
scientific and medical community. And the National Academy of
Sciences was specifically chartered to advise the Government on
critical scientific issues, which it has done very ably over the
years. PMA knows first-hand that the Institute of Medicine

already is deeply involved in the efforts to combat AIDS.

In responding to the AIDS epidemic, the FDA is acting
swiftly and effectively. Officials at all levels of the agency--
from Commissioner Frank E. Young on down--are working extremely
hard in cooperating with our companies to hasten the approval of
drug and diagnostic products to combat AIDS and its

complications.

It has been suggested that the country needs a crash program
to combat AIDS organized along the lines of the Manhattan Project
to develop the atomic bomb or the Apollo program to land a man on
the moon. We do not believe such an effort would be productive..

Nor do we believe that a single person or government entity ,

 

 
 

 

should be given overall authority to direct the efforts to combat

AIDS.

The Manhattan and Apollo projects were massive engineering
enterprises that used existing scientific knowledge to accomplish
specific programmatic objectives. One of the major difficulties
with AIDS is that many fundamental scientific questions remain
unanswered, as I have noted. To ensure that scientific research
proceeds as rapidly as possible, the Federal budget must provide
adequate funding to support all legitimate AIDS research
proposals for such funding. In addition, research by private
Organizations should be encouraged, so.a rich diversity of
approaches will be pursued. Development and marketing of
products is best accomplished by the private sector, which, as I
have indicated, develops and markets all of the drugs and
vaccines introduced in the United States. Establishing a single
director or bureaucracy to decide what research should be
pursued, and what discoveries should be developed, would be an
enormously counter-productive step that would threaten the

expeditious development of AIDS therapies.

SUMMARY

e The research-based pharmaceutical industry fully

appreciates the urgency of discovering and developing drugs to

combat AIDS, and has mounted intensive efforts to that end.

 

 
 

‘@ Fifty-five pharmaceutical companies are developing,
or. have developed, 77 products to diagnose, prevent and treat

AIDS.

e The industry supports the conduct of basic research,
public and private, to gain scientific knowledge about the HIV

virus and its effects.

e The Institute of Medicine should be designated as
the forum where the government, academic scientists and private
industry can meet to assess progress in the battle against AIDS,
resolve problems as they emerge and thoroughly consider all
relevant issues, including the role and administration of the

AIDS Testing and Evaluation Units.

@ The Food and Drug Administration should be
encouraged, and provided sufficient resources, to continue its
efforts to expedite the approval of safe and effective drugs and

diagnostic products to combat AIDS.

e Diversity of research and development efforts should
be preserved as the best way to ensure progress in the battle

against AIDS.

Mr. Chairman, that concludes my prepared remarks. I would
be pleased to respond to any questions that you and other members

of the Commission may have.

 
 

 

  

APPENDIX A

AIDS PRODUCTS IN DEVELOPMENT

 

January 1988

Presented by the Pharmaceutical Manufacturers Association

Survey Tracks
Progress in Development
of AIDS Products

t least 77 AIDS-related
drugs, diagnostics and

vaccines are available or in |

development, according to the
quarterly survey by the Pharmaceu-
tical Manufacturers Association
(PMA). Fifty-five companies are
involved in the effort.

Two AIDS drugs and nine diag-
nostics already are approved and
available. The drugs are Retrovir
(zidovudine, Burroughs Wellcome),
used to treat AIDS and advanced
AIDS related complex (ARC), and
Pentam 300 (pentamidine isethio-
nate, LyphoMed), used to treat
pneumocystis carinii pneumonia, a
common opportunistic infection in
AIDS patients.

The 77 products in the survey
include 16 anti-virals, 22 immuno-
modulators, three anti-infectives,
26 diagnostics and 10 vaccines.

The survey, taken in January,
showed an increase of 13 products
over the last survey. New are the
immuno-modulator gamma inter-
feron from Genentech and the anti-
infective fluconazole from Pfizer.
Oncogen, Otisville BioPharm and
Wistar Institute are developing
vaccines. New diagnostics are the
Cetus/Eastman Kodak SureCell to
detect HIV antibodies and another

 

product to amplify and detect HIV
viral DNA; Cambridge Bioscience’s
two Recombigen tests for detecting
HIV antibodies; Gen-Probe’s test
for detecting AIDS virus; Organon
Teknika’s Vironostika to detect
antibodies to HIV antigen; Viral‘
Technologies’ product to detect
HIV p17 antibodies; and RIBA
HIV216, under development by
Chiron to be marketed by Ortho
Diagnostics.

Companies working on the 77
anti-AIDS products include many of
the country’s largest pharmaceu-
tical firms—Abbott, American
Cyanamid, Burroughs Wellcome,
Ciba-Geigy, DuPont, Genentech,
Hoffmann-La Roche, Merck,
Merrell Dow, Ortho, Pfizer, Sandoz,
Schering-Plough, Syntex, Upjohn
and Warner-Lambert—as well as
many small, highly-specialized
research firms.

“The diversity of research on
AIDS drugs is one of the most
encouraging factors in the search
for a remedy,’ said PMA President
Gerald J. Mossinghoff. ‘(Companies
throughout the industry are pur-
suing widely differing approaches,
greatly enhancing the prospects for
discovery.’

Thirty-nine products have

 

progressed to clinical trials. Of the
drugs, 11 are in Phase I testing, six
are in Phase I/II, six are in Phase
Il, three are in Phase I/II, and
seven are in Phase III. Exact status
of six products could not be
determined.

Phase I tests usually involve only
a few people and are intended to
determine the drug’s pharmacologi-
cal actions—its safe dosage range,
how it is absorbed and metabolized,
and its duration of action. Phase II
and III tests involve increasing
numbers of patients to determine
the effectiveness of the product. If
the testing successfully demon-
strates the product’s safety and
effectiveness, the test data then are
submitted to the Food and Drug
Administration as a New Drug
Application (NDA) for review and
market approval.

For the average pharmaceutical,
the process of pre-clinical develop-
ment, clinical testing, and NDA
review requires seven to 10 years,
but the Food and Drug Administra-
tion has established special review
procedures intended to speed
review of AIDS-related drugs and
vaccines.

A more detailed explanation of
the drug approval process is included.

 

 
 

 

AIDS Products In Development

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Anti-virals
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
AL-721 Ethigen ARC, PGL | IND approved
(AL-721) (Los Angeles, CA) Phase ;
Betaseron Triton Biosciences AIDS, Kaposi’s sarcoma, ARC IND approved
(interferon beta) (Shell Oil) Phase
(Alameda, CA) =
Cytovene’ : Syntex CMV A Pending
(ganciclovir) (Palo Alto, CA) (Orphan Drug)
DDC Hoffmann-La Roche AIDS, ARC IND approved
(dideowycytidine) (Nutley, NJ) Phase I/II
(dextran sulfate; Ueno Fine Chem Industry AIDS, ARC IND approved
UA001) (Osaka, Japan) Phase I
Foscarnet Astra Clinical Research HIV infection, CMV retinitis IND approved
(trisodium (Hopkinton, MA) Phase I/II
phosphonoformate)
HPA-23 Rhone-Poulenc Sante HIV infection IND approved
(Monmouth Junction, NJ) Phase I
Ornidyi Merrell Dow PCP NDA pending
(¢flornithine) (Cincinnati, OH) (Orphan Drug)
Peptide T Peninsula Labs AIDS IND approved
(octapeptide sequence) (Belmont, CA) Phase I
Reticulose Advanced Viral Research AIDS, ARC IND submitted
(nucleophosphoproten) (Miami, FL)
Retrovir Burroughs Wellcome AIDS, adv. ARC NDA approved
(zidovudine; AZT) (Rsch. Triangle Park, NC) -— -_—
pediatric AIDS, Kaposi’s sarcoma, IND approved
ésymptomatic HIV infection, less severe Phase I/II
, neurological involvement, in com-
. bination w/other therapies
Rifabutin Adria Labs ARC IND approved
(ansamycrn LM 427) (Dublin, OH) Phase IT
(trimetrexate) Warner-Lambert PCP IND approved
(Morris Plains, NJ) Phase On
Virazole ViratekK/ICN AIDS, Kaposi's sarcoma, ARC - IND approved
(nbavrin) (Costa Mesa, CA) Phase II/III
Wellferon Burroughs Wellcome Kaposi’s sarcoma, HIV, in combination IND approved
(alpha interferon) _(Rsch. Triangle Park, NC) w i Phase I
Zovirax Burroughs Weilcome AIDS, ARC, in combination w/Retrovir IND approved
(acyclovir) (Rsch. Triangle Park, NC) Phase I
Immuno-modulators
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
ABPP Upjohn Advanced AIDS, Kaposi’s sarcoma IND approved
(bropirumine) MI Phase I/II
AS-101 Scientific Testing AIDS IND approved
(National Patent Develop- “PP
ment, Bar Ilan University,
Israel)
(New York, NY)
Ampligen DuPont ARC, PGL IND approved
(mismatched RNA) (Wilmington, DE) Phase III
HEM Research
(Rockville, MD)
(anti-human alpha Advanced Biotherapy AIDS, ARC IND approved
interferon antibody) Concepts Phase |
(Rockville, MD)
Carrisyn Carrington Labs ARC IND submitted
(acemannan) (Irving, TX)
Colony Stimulating Sandoz AIDS, Kaposi’s sarcoma, ARC, HIV IND approved
Factor (East Hanover, NJ) Phase I
(GM-CSF) Genetics Institute
(Cambridge, MA)

 

Provided as a Public Service by the Pharmaceutical Manufacturers Association.

 

 
 

 

-]0Q-

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Immuno-moduiators
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
CL246, 738 American Cyanamid AIDS IND approved
(CL246, 738) (Pearl River, NY) Phase I/II
(gamma interferon) Genentech ARC, in combination w/TNF (tumor IND approved
(S. San Francisco, CA) necrosis factor) clinical trials
IMREG-1 Imreg AIDS, Kaposi’s sarcoma, ARC, PGL IND approved
(New Orleans, LA) Phase III
IMREG-2 Imreg AIDS, Kaposi’s sarcoma, ARC, PGL IND approved
(New Orleans, LA) Phase I]
Imuthiol Merieux Institute AIDS, ARC -IND approved
(diethyl dithio (Miami, FL) Phase
carbamate) -
IL-2 Cetus AIDS, Kaposi’s sarcoma IND approved
(interleukins) __—_ (Emeryville, CA) Phase Il
IL-2 Hoffmann-La Roche Kaposi’s sarcoma IND approved
(interleukin-2) (Nutley, NJ) Phase III
Immunex
(Seattle WA)
INTRON-A Schering-Plough Kaposi’s sarcoma NDA filed
(interferon alpha) (Madison, NJ)
Isoprinosine Newport Pharmaceuticals ARC, PGL, HIV seropositive IND approved
(inosine pranobex) (Newport Beach, CA) asymptomatic patients Phase
(methionine TNI Pharmaceuticals AIDS, ARC Investigator’s IND approved
enkephalin) (Chicago, IL) Phase I/II
MTRPE Ciba-Geigy Kaposi's sarcoma IND approved,
(muramyl-tripeptide) (Summit, NJ) Phase I
opentin Ortho Pharmaceuticals HIV infection IND approved
) (Raritan, NJ) Phase I/II
(thymic compound)
Roferon-A Hoffmann-LaRoche Kaposi's sarcoma NDA filed
(interferon alpha) (Nutley, NJ)
(recombinant Ortho Pharmaceuticals severe anemia assoc. w/AIDS and AZT IND approved
erythropovetin) (Raritan, NJ) therapy Phase II
Trexan DuPont AIDS, ARC early Phase IT
(naltrexone) (Wilmington, DE) _
TNF Genentech ARC, in combination w/gamma IND approved
(tumor necrosis (S. San Francisco, CA) interferon clinical trials
factor)
Anti-infectives
DRUG NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
Pentam 300 hoMed PCP NDA approved
(pentamidine mont, IL)
isethionate, IV
dosage)
aerosol dosage PCP prophylaxis IND approved
Phase ITI
PCP treatment IND approved
Phase III
(fluconazole) Pfizer cryptococcal meningitis, candidiasis IND approved
(New York, NY) re 2 Phase lll
Diagnostics
TEST NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
HTLV3-EIA Abbott Labs detects HIV antibodies licensed
(N. Chicago, IL)
To Be Announced Abbott Labs detects HIV antigens pending FDA approval

(N. Chicago, IL)

 

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ARC—AIDS related complex.
CMV—Cytomegalovirus. An opportunistic in-
fection that can cause blindness and be fatal in
AIDS patients.

CNS—central nervous system.

antibodies.

HIV—Human immunodeficiency virus.
Previously called HTLV-II or LAV.
IND—Investigational New Drug.

Orphan drug—Indicated for rare diseases.

I
-ll-
Diagnostics
TEST NAME MANUFACTURER INDICATION DEVELOPMENT STATUS
Envacor Abbott Labs detects antibodies to core antigen p24 pending FDA approval
(N. Chicago, IL) and the envelope antigen p41
Recombigen Cambridge Bioscience detects HIV antibodies pending FDA approval
Latex (Worcester, MA)
(rapid HIV antibody
test)
Recombigen EIA Cambridge Bioscience detects HIV antibodies pending FDA approval
HIV (Worcester, MA)
(two-hour
immunoassay)
HIV ELISA Cellular Products detects HIV antibodies licensed
(Buffalo, NY)
(Eastman Kodak, marketer,
Rochester, NY)
SureCell Cetus detects HIV antibodies in development
(Emeryville, CA) (
Eastman Kodak
(Rochester, NY)
To Be Announced Cetus amplifies and detects HIV viral DNA in development
(Emeryville, CA)
Eastman Kodak
(Rochester, NY)
RIBA HIV216 Chiron validates results of positive ELISA test clinical trials
(Emeryville CA)
(Ortho Diagnostics,
marketer, Raritan, NJ)
HIV ELISA DuPont detects HIV antibodies licensed
Antibody Kit (Wilmington, DE)
HIV Western Blot DuPont/Biotech validates results of positive ELISA test licensed
Kit (Wilmington, DE)
HIV p24 core DuPont detects HIV p24 pending FDA approval
antigen test (Wilmington, DE) core antigen
Rapid HIV DuPont detects HIV antibodies clinical trials
antibody test (Wilmington, DE)
VIRGO HIV Electro-Nucleonics detects HIV antibodies licensed
ELISA (Fairfield, NJ)
VIRGO HIVIFA _ Electro-Nucleonics detects HIV antibodies pending FDA approval
(vmmunofluorescence (Fairfield, NJ)
assay)
LAV EIA Genetic Systems detects HIV antibodies licensed
(Seattle, WA)
To Be Announced Gen-Probe test for AIDS virus early research stages
(San Diego, CA)
To Be Announced ater Roche detects HIV antibodies pending FDA approval
uley,
MGSearch MicroGeneSys detects HIV antibodies clinical trials
HIV-160 (West Haven, CT)
ELISA Ortho Diagnostics detects HIV antibodies licensed
(Raritan, NJ)
Bio-EnzaBead Organon Teknika detects antibodies to HIV antigen in licensed
(HIV ELISA) (Durham, NC) serum or plasma
LEGEND:
AIDS—Acquired Immune Deficiency ELISA or EIA—enzyme-linked immuno- PCR—Pneumocystis carinii pneumonia. A com-
Syndrome. sorbant assay. Used to screen blood for HIV mon opportunistic infection in AIDS patients.

PGL—persistent generalized lymphadenopathy
Phase I—safety testing and pharmacological
profiling in humans

Phase Il—effectiveness testing in humans
Phase ITI—extensive clinical trials in humans

 

 

 
 

 

 

Diagnostics

 

TEST NAME MANUFACTURER

INDICATION

DEVELOPMENT STATUS

 

Vironostika Organon Teknika
(HIV Microelisa (Durham, NC)
To Be S Ss
Announced tex/Syva
Palo Alto, CA)

Cambridge Bioscience

(Worcester, MA)

detects antibodies to HIV antigen in
serum or plasma °

test for AIDS antibodies

licensed

in development

 

To Be Announced 5S Syva
o Alto, CA)

test for AIDS virus

in research

 

Fluorognost Thermascan
(immunofluorescence (New York, NY)
assay)

HIV-1 antibody confirmation test

IND approved

 

To Be Announced Viral Technologies

(Interleukin-2, Alpha-1

Biomedicals)
(Washington, DC)
Vaccines

detects HIV p17 antibodies

in development

 

MANUFACTURER

INDICATION

DEVELOPMENT STATUS

 

Biotech Research Labs
(Rockville MD)
Ciba-Geigy

(Summit, NJ)

Chiron

(Emeryville CA)
Genentech
(S. San Francisco, CA)

AIDS early research phase

AIDS animal studies

AIDS early research phase.-

 

Institut Merieux
(Lyon, France)
Cambridge Bioscience
(Worcester, MA)

AIDS early research stages

 

VaxSyn HIV-1-
MicroGeneSys
(West Haven, CT)
Oncogen

(Seattle WA)
Otisville BioPharm
(Otisville NY)

Repligen

Cambridge, MA

Mar es

(Rahway, NJ)

Viral Technologies

(Interleukin-2,

Alpha-1 Biomedicals)
ashington, DC)

Wistar Institute

(Philadelphia, PA)

AIDS Phase I

AIDS Phase I

AIDS early research phase

AIDS animal studies

AIDS IND submitted

AIDS IND submitted

 

The content of this chart has been obtained through government and industry sources (including FDA and NTH) based on the latest
information. The information may not be comprehensive For more specific information about a particular product, contact the in-

dividual company directly.

 

Copyright © 1988 by the Pharmaceutical Manufacturers Association. Permission to reprint 1s awarded if proper credit s given.

 

 
 

 

~13-

The Drug Approval Process

 

The U.S. system of new drug Administration (FDA), showing the Phase II. Pilot Efficacy Studies:
approvals is perhaps the most results of all animal testing and how | This phase consists of controlled
rigorous in the world. Here ishowa | the drug is made. The IND becomes studies in approximately 200 to 300
drug is tested and approved. effective if FDA does not disapprove | volunteer patients to assess the
the application in 30 days. drug’s effectiveness. Simultaneous

Preclinical Testing. The Human Testing (Clinical). There | animal and human studies continue
promising agent is first subjected to | are three phases of human testing, to determine the drug’s safety. Phase
extensive laboratory and animal each involving larger numbers of I clinical testing may require about
testing to determine answers to two | people than the one before. two years to complete.
key questions: Is the compound Phase I. Safety Studies and Phase IIT. Extensive Clinical
biologically active? Is it safe? If the Pharmacological Profiling: This , Trials: Here the testing moves to
answers to both appear to be | phase determines the drug’s larger numbers of volunteer patients
affirmative, the drug sponsor is pharmacological actions, its safe — usually 1,000 to 3,000, in clinics
ready to test in humans. This stage | dosage range, how it is absorbed, and hospitals. The drug is
generally lasts from one to two distributed, metabolized and administered by practicing
years. excreted, and the duration of its physicians to those suffering from

Investigational New Drug. action. These tests involve a small the condition the drug is intended to
Before human tests can start, the number of normal healthy subjects treat. These studies must confirm
drug sponsor must file an Inves- (not patients). Phase I clinical testing | earlier efficacy studies and identify
tigational New Drug (IND) can usually be conducted in less than | low-incidence adverse reactions.
application with the Food and Drug | one year. Phase III clinical trials last about

three years.
New Drug Application (NDA).

 

‘THE STEPS TOWARD DRUG APPROVAL

Following completion of Phase III,
the drug sponsor-must file an NDA

 

 

 

 

 

 

 

ACTION with the FDA, containin gall the
. FDA Approval information the sponsor
6. FDA App gathered. NDAs typically run into
5. FDA thousands of pages. The information
Review submitted must include the chemical
structure of the drug, scientific
4.Company rationale and purpose, animal and
Files NDAwithFDA laboratory studies, results of all tests
- in humans, formulation and
Phase Three: production details, and proposed
Extensive Clinical Trials labeling. On average, the NDA review
. and app process by FDA takes
Phase Two: two to three years.
Testing Efficacy Approval. Once an NDA is
approved, the company is required to
3. Clinical Studies periodically submit reports to FDA,

Phase One: Pharmacological Profile

including adverse reaction data and

 

2. Company Files IND with FDA

f
i

1. Laboratory and Animal Studies

production, quality control and
distribution records. For some drugs,
FDA requires affirmative post-
marketing monitoring, or additional
studies to evaluate the long-term
effects.

 

 

Pharmaceutical
Mianufacturers
Association

 

 

1100 15th Street NW - Washington, DC 20005

mae
qa

- Telephone (202) 835-3400

 

 
 

 

-14- APPENDIX B

PHARMACEUTICAL RESEARCH AND DEVELOPMENT

The hallmark of the pharmaceutical industry is its
investment in research and development--to produce new and more
effective medicines. "There is perhaps no industry that depends
as heavily on new products--and thus on research and development
--as does pharmaceuticals," according to the February 23, 1987
edition of Forbes. As the chart below shows, the research-based
pharmaceutical industry has doubled its investment in research
and development every five years since 1970. This trend
continued in 1987, when the industry invested a record $5.4
billion on research and development--a 14.9 percent increase over

the $4.7 billion spent in 1986.

R&D EXPENDITURES BY Pharmaceutical

Manufacturers

PMA MEMBER FIRMS Association

Expenditures ($ Billions)

 

 

5

 

 

 

1970 1975 1980 1985 1987"
Source PMA Annual Survey Year “Budgeted

 

 
 

 

To finance this mounting investment in research and

development, pharmaceutical companies have used an increasingly
larger proportion of U.S. sales revenues. From 1973 to 1980, the
U.S. research-based pharmaceutical industry invested between 11.1
percent and 11.7 percent of U.S. sales in research and
development. In 1981, the industry increased its investment to
13.1 percent of sales, and, in 1987, PMA member companies
invested an estimated 15.1 percent of their domestic sales and

exports in research and development.

Pharmaceutical companies have continued to increase their
funding for research and development even though pharmaceutical
research is an expensive, time-consuming and risky business. The
average cost of developing a new drug is about $125 million, as
shown in a new study--The Cost of Developing a New Drug--by
Steven N. Wiggins, Rex B. Grey Professor in the Department’ of
Economics at Texas A&M University. Thousands of new compounds
are screened for each new molecular entity that eventually is
approved for marketing. On average, it takes from seven to 10
years from the time a new drug is discovered until the drug is

introduced on the market.

 

 
 

 

THE DEVELOPMENT AND USE OF AZIDOTHYMIDINE IN THE TREATMENT OF HUMAN
IMMUNODEFICIENCY VIRUS INFECTIONS

Written testimony to be given to the President's Commission on AIDS
February 19, 1988, New York City

DAVID W. BARRY, M.D.

WELLCOME RESEARCH LABORATORIES
BURROUGHS WELLCOME CO.

NORTH CAROLINA

Burroughs Wellcome Co. first became directly involved in efforts to discover

and develop therapy for the treatment of the Acquired Immune Deficiency Syndrome
(AIDS) and associated infections in 1980, a year before the illness was described
as a syndrome by the USPHS Centers for Disease Control (8,9). The company's
initial involvement was based upon the fact that many of the drugs used to

treat the opportunistic infections associated with AIDS are manufactured by
Wellcome. In that year, we began to receive a number of calls requesting
intravenous Septra® for the treatment of adult patients with Pneumocystis
carinii pneumonia (PCP). At that time the intravenous preparation of Septra

was not approved in the United States for general use, but was available

under a treatment IND program. Initially, we were somewhat skeptical of the
increase in requests for Septra because, until that time, episodes of PCP
generally occurred primarily in children who had received intensive chemotherapy
for leukemia. Approximately a year later, epidemiologic studies showed that

PCP was one of the prime manifestations of AIDS (8,9). In addition, we have
supplied pyrimethamine (Daraprim®), leukovorin (Wellcovorin®), acyclovir
(Zovirax®), DHPG (BW 759U, ganciclovir) and interferon (Wellferon®) to treat
various opportunistic infections or tumors occurring in AIDS patients. Because
of this involvement, scientists at Wellcome became familiar with the disease
during the early 1980s. In addition, Wellcome has a long history of the
development of antiviral therapy, including the development of Marboran® for

the treatment of the complications of smallpox vaccination in the 1960s,
trifluorothymidine (Viroptic®) for ocular herpes infections in the 1970s and

then acyclovir (Zovirax®) for herpes infections in the 1980s.

SL/t1/D11/22
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In 1984 Drs. Francoise Barre“-Sinnoyssi, Robert Gallo and Samuel Broder served
as a catalyst to increase B.W. Co.'s involvement in the development of therapies
for the disease syndrome known then as AIDS. They came to the Wellcome Research
Laboratories to talk about the newly discovered retrovirus, termed HTLV ITI

or LAV, which, at that time, had been cultured from nearly 50 AIDS patients
(4,35). This virus has subsequently been termed the Human Immunodeficiency
Virus or HIV. It was at this time that the decision was made at B.W. Co. to
test some of our compounds for activity against the newly discovered retro-
virus. In our research laboratories were several compounds which had been
studied for antiviral and antibacterial activity and which were subsequently
tested for activity against HIV.

Among those tested was a compound which was activated by cellular thymidine
kinase; the compound was an analogue of thymidine with an azido group replacing
the 3'-hydroxyl group of thymidine. This compound, known initially as compound
BW 509U is now known as azidothymidine, AZT, zidovudine or Retrovir®. As a
very close analogue of thymiaine, the azido replacement does not interfere

with efficient phosphorylation by cellular thymidine kinase (17,41). A2T

had initially been synthesized in 1964 by Dr. Jerome Horwitz at the Michigan
Cancer Foundation as a potential anti-cancer agent, but studies with the
compound were abandonea shortly thereafter becauSé of a lack or activity
against animal cancers (23). Wellcome resynthesized it in the early 1980s

ana cunducted a uuwer of studies which showed that it was quite active against
many aerobic gram-negative bacteria (14). Studies in November of 1984 with

two murine retroviruses (Harvey Sarcoma Virus and Friend Leukemia Virus)
suggested that it might be highly active against the human immunodeficiency
virus. At that time Wellcome did not have laboratory facilities to test it
against the AIDS virus, so it was sent to Dr. Broder at the National Cancer
Institute in the United States, who confirmed 1ts activity against HIV (31).
Its mechanism of action against HIV is analogous to that against bacteria in
that AZT must be converted to an active phosphorylated form. AZT is first
phosphorylated to AZT 5'-monophosphate by cellular thymidine kinase (17).
Subsequent phosphorylation by other cellular kinases yields AZT diphosphate
and AZT triphosphate (AZT-TP). The latter is a selective inhibitor of retroviral

reverse transcriptase (41). In addition, because the azido group prevents

SL/t1/D11/22
THZZ/88/0028/2

 

 
 

 

the necessary 3'-5' phosphodiester bonds required for DNA elongation, AZT-TP

also acts as a viral DNA chain terminator (14,43).

After confirming AZT'’s anti-HIV activity in February of 1985, Wellcome scientists
conducted a rapid series of preclinical studies, including toxicology, pharma-
cology, and pharmacokinetic studies. These studies suggested that trials in
tuuaus should proceed. A Phase I study began in July of 1985, and was a
collaboration between the National Cancer Institute and Duke University sponsored
by Burroughs Wellcome Co. This study was conducted in patients infected

with HIV who had been diagnosed as having AIDS or ARC. The results indicated

AZT was well absorbed orally, with dose-independent kinetics observed over a
fairly wide dosing range (29). AZT was shown to be 65% bioavailable (44),

but in reality, may be as high as 100% bioavailable. This discrepancy results
because there is a first pass metabolism effect in which a portion of the

AZT is converted to AZT-5'-glucuronide as the result of glucuronidation in

the liver (26). Both peak and trough levels that were above the in vitro
sensitivity of the virus were achieved in these studies, suggesting that

anti-HIV effects might be possible in man (27,31,33). In addition, it was

found that AZT penetrated the blood-brain barrier quite well (26), suggesting
that viral infections in brain could be treated (17). The significant
glucuronidation of AZT may be an important factor since other drugs which

are glucuronidated, such as acetaminophen, may have some effect on the metabolism
of AZT (25).

When the Phase I studies were completed in January of 1986, we had a very
diffienlt decision as to how to proceed. Traditionally, early clinical studies
of new drugs proceed in a very regimented way. New drugs are typically tested
in normal, healthy volunteers. to evaluate safety and tolerance and then the
new drug is examined in a larger number of patients to evaluate its efficacy
and safety profile, usually in patients with milder stages of the disease in
question. There are many reasons for this approach. The first is that any
toxicity seen is likely to be milder in patients whose baseline physical

status is relatively good. More importantly, the Likelihood of therapeutic
success in less ill patients is often greater in these patients than in those

who are at a more severe stage of their disease. We know from experience

SL/t1/D11/22
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with antibiotics, for example, that many patients who are severely granulocy-

topenic secondary to intense cancer chemotherapy have infections which will
often not respond to antibacterial agents which are known to be quite effective
in less ill patients, simply because their illness is so advanced and their
immune status compromised. In the case of AZT, however, Wellcome believed

that there were two counterbalancing elements which requireu wiat a Less
classical approach be taben. The first was that there were a large number

of people, possibly nundreas per week, dying of AIDS at the time the Phase I
Study was completed in January, 1986. Wellcome also believed that testing

AZT in patients with advanced manifestations of HIV infection was the most
vigorous test to determine its therapeutic index. If it proved to be effective
in the most severely ill patients, while exhibiting manageable adverse effects,
then it might be more beneficial in patients with milder forms of disease.

We therefore made a difficult decision to conduct a double-blinded, placebo-
controlled study in advanced AIDS and ARC patients in February of 1986. The
results of this study have been published (15,36) so only a brief review and

update of data gathered since then are necessary.

One of the most difficult and key issues in the study was the decision to
administer placebo to half of the patients enrolled. This study was initiated
at a time when the Phase I study had given only hints that the drug might be
effective. Yet with hundreds of people dying, and the publication of the

Phase I study which described potentially beneficial therapeutic effects in

man (44), there arose a number of ethical and scientific questions concerning
the conduct of a placebo-controlled study (5). Nevertheless, we believed

that this drug must be proven, by classical clinical research methodology,

to be both safe and effective, or otherwise many patients might be put at

risk without knowledge of the actual benefits of the drug. In order to assure
that the risk and benefits of AZT were evaluated adequately without withholding,
for any longer than necessary, a promising ‘therapy, it was agreed to appoint

a Data Safety and Monitoring Board whose members would examine data from the
ongoing study every two months and make recommendations about how to proceed.
After analysis of various safety and efficacy parameters, the board of medical
experts was to advise Wellcome whether one group was experiencing significantly

greater side effects or greater benefit from therapy than the other group.

SL/t1/D11/22
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TT

From this analysis, the board was to recommend whether it would be unethical

to proceed.

In this study, 282 AIDS and ARC patients were entered at 12 university-associated
medical centers in the United States between January and June of 1986. In

order to have as uniform and comparable groups as possible between drug and
placebo, narrow categories of disease progression were Studied. For the

AIDS component, only those patients who had experienced their first episode

of PCP within the prior four months were entered in the study. ARC patients
were enrolled if they had a number of symptoms including, among others, weight
loss, sustained fever for over a month, and/or extensive oral candidiasis.

All patients were required to have fewer than 500 CD4 cells and to have complete
cutaneous anergy to four common antigens. The vast majority of patients had
fewer than 200 CD4 cells. Patients with Kaposi's sarcoma, intravenous drug
abusers and children were excluded from this study. The drug and placebo

groups were quite comparable in a variety of baseline characteristics that

were examined.

On September 19, 1986, the Data Safety and Monitoring Board recommended to
Wellcome that the study should be terminated because a significantly higher
mortality rate in the placebo group compared to the therapy group was found.
Since patients were enrolled at different times, the length of time on drug
ranged from 10 to 28 weeks, with an average of 17 weeks. Analysis of the
data at that time indicated that, when compared to placebo, AZT recipients
had significant improvements in the. number of CD4 cells, delayed cutaneous
hypersensitivity, weight gain, activities of daily living and neurologic
function (15). 4m addition, azi recipients had significant decreases (in
many cases to an undetectable level) of previously circulating P24 antigen
(10) and significant decreases in the frequency and severity of opportunistic
infections. Most importantly, the probability of death within six months of
initiating therapy was 22% for the placebo group and 2% for the drug treated

group.

Symptomatic adverse reactions were extremely common in both groups (36).
This may have been the result of the complicated nature of the underlying

SL/t1/D11/22
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disease. Nausea, myalgias, insomnia and headache, however, were somewhat

more common in the drug treated group. The most significant toxicity was
myelosuppression which was dependent upon dose and duration of therapy, as

well as upon pre-existant bone-marrow reserve. Up to 45% of patients with

poor bone-marrow reserve had significant decreases in either red cell and/or
white cell numbers during the observation period. The incidence of such
decreases in patients with better marrow reserve was only slightly higher

than that in the same subset of individuals in the placebo group. The management
of such myelosuppression was left to the judgement of the individual investigator.
Although there was great heterogeneity of practice, the bone marrow suppression
could generally be managed py aose reduction, dose interruption, transfusion

or a combination of these approaches.

At the time the placebo-controlled portion of the study was terminated, all
patients, including those originally randomized to receive placebo, were

offered the opportunity to receive AZT in an unblinded fashion provided they
agreed to continued follow-up by the original investigator. While most of

the patients agreed to continue taking AZT, a small number elected to leave

the study for a variety of reasons. Some, particularly in the original placebo
group, were moribund and their physicians felt that their terminal status

would not be improved by additional therapy. Other moribund patients originally
assigned to the placebo cohort received drug for only a few days or weeks

before expiring. Conversely, some patients originally assigned to receive

AZT subsequently stopped taking it because of real or perceived adverse reactions.
Some patients in both groups withdrew because of a desire to avoid the rigorous

follow-up required.

Because of these factors, ‘continued follow-up and comparison of the two groups
has been particularly difficult. However, if comparisons are made in which
patients who originally received placebo are considered only if they had
received no AZT or AZT for less than three weeks, and AZT recipients are
included if they received active drug until at least 2 months before expiring,
the survival rate of the AZT treated group was 98%, 94%, 88%, 85% and 78% at
6, 9, 12, 15 and 18 months respectively since entry into the study, compared
to a survival of 76% and 52% at 6 and 9 months in the placebo group. Survival

SL/t1/D11/22
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was even further improved to 91% and 84% at 12 and 18 months in those patients
receiving prophylaxis for PCP in addition to receiving A2T.

Too few patients in the original placebo group remained after 9 months to
provide meaningful comparisons. In fact, only four of the 28 patients originally
assigned to placebo who did not elect to receive AZT after unblinding of the
study, or who received it for less than 3 weeks were alive one year after
initiation of the study, and all are now dead. Thus, comparison of survival
of patients on AZT for greater than 9 months must be compared to historical
controls. These comparisons are, however, less than ideal because historical
groups may represent a significantly different patient cohort, and because

of the very incomplete follow-up of individual patients in most epidemiologic
studies which are used for this comparison. Also, most epidemiologic studies
use spontaneous reporting of death or registration of death certificates
specifying death from AIDS within a particular locale to make their projection
of survival rates. Both of these factors lead to significant under-reporting
of deaths (37). It is known that AIDS patients are a highly mobile population
often moving to other locales from those where the original diagnosis was
made. In addition, physicians do not always list AIDS as the cause of death
on death certificates. For example, a study which made extensive efforts to
track down purported "longer term survivors" of AIDS found that at least 58%
of such patients, in fact, were dead (32,37).

With these caveats in mind, the best historical comparison to the original
cohort of patients who were randomized to AZT in the study is a cohort of

AIDS patients in New York City in 1985 who had their diagnosis made exclusively
on the basis of PCP (37). Their minimum one year mortality from the date of
PCP diagnosis was 51%. Mortality was probably significantly greater because
only those patients who had AIDS listed as their cause of death on a death
certificate that was registered in New York City were considered to be dead

in the study. Because AIDS patients in the original double-blind, placebo-controll.
study began taking AZT about 2} months after their initial episode of PCP,
their 13% mortality at one year after diagnosis of PCP and 21% after entry

into the study is one-fourth to one-half the minimal mortality reported in

the New York study. For purposes of direct comparison, in the double-blind,

SL/t1/D11/22
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placebo-controlled study, the mortality rate of 12% in the AZT-treated AIDS
patients at 9 months was less than one fifth the 61% 9-month mortality rate

of the AIDS patients who did not receive AZT or who received it for less

than three weeks. The higher mortality in this placebo group (61% at 9 months)
compared to the New York passive surveillance group (at least 51% at 12 months)
may be related to a sicker population in the AZT study, better follow-up and
recording of deaths, or other unidentified confounding factors.

Future follow-up in the original AZT and placebo cohorts and subsequent relevant
mortality comparisons will become increasingly difficult because of anticipated
loss of patients to follow-up and because of the possible decision of some
patients to discontinue drug for a variety of reasons. In addition, management
of both adverse reactions and the prevention and treatment of opportunistic
infections varies widely among centers, thereby making the patients progressively
less homogenous. For example, some physicians continue to give full doses

of AZT in the face of significant myelosuppression and treat anemia with
substantial numbers of transfusions. Others used to more benign (curative)
drugs with huge therapeutic indices, decrease or temporarily discontinue
therapy when even moderate anemia or granulocytopenia occurs. Furthermore,

the use of prophylaxis with Septra, aerosolised pentamidine or dapsone, each

of which has ‘been shown to substantially diminish the incidence of PCP (12),

. is not standardized in these patients.

The de“nouement of the original double-blind, placebo-controlled study in
September of 1985 provided another opportunity to study a large cohort of
patients. Wellcome set up a program, in conjunction with the National Insti-
tutes of Health, to dispense AZT free of charge to any AIDS patient in the
United States who had had PCP at any time in the past, and who fulfilled
minimum entry criteria. ARC patients were not included in this program because
tne FDA was still analyzing data concerning them at that time. Approximately
4800 AIDS patients received AZT under this "treatment IND", "compassionate
plea" or "named patient" program between October, 1986 and March, 1987 when

the drug became available by prescription. The characteristics of

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the patients in this study were generally similar to those of AIDS patients

in the general population, with the vast majority being homosexual or bisexual.
Nevertheless, a number of patient categories not well represented in the

Phase II double-blind, placebo-controlled study did participate in this
uncontrolled study. There were neariy 150 women and over 250 intravenous

drug abusers. ‘In addition, 424 patients were hispanic and over 500 were

black. -Although AZT was approved for general use in March of 1987, we were
able to monitor the survival of these patients until September 15, 1987,

when the controlled distribution program that was in place during that interval
was dismantled. The amount of data that can be obtained during “treatment

IND" studies is generally limited, but sufficient controls were instituted

in this program so that mortality statistics are reasonably reliable, at

least for a 9 month period. After adjusting for the fact that significantly
Sicker patients could participate in this program, overall survival data

were very Similar to that observed in the original placebo-controlled study.

The incidence of adverse reactions was somewhat less than noted in the original
placebo-controlled study, and may have been the result of less intensive
observation and management of the patients or less aggressive reporting of

such reactions. Although significantly higher rates of death have been reported
in untreated women and drug addicts with AIDS when compared to male homosexuals
with AIDS (37), no such differences were noted if these patients were receiving
AZT. Likewise, no differences in mortality were noted between black and white
AIDS patients receiving AZT. Surprisingly, survival among hispanics was
Slightly higher than among whites, or. blacks, but it is unclear whether this

is significant. The highest mortality rates were recorded during the first
eight weeks of study, indicating the very advanced state of illness of many

of the participants. Over 100 patients, in fact, died in the 1-2 week interval
between the request for drug and its receipt in the pharmacy. The mortality
rate of people who had acquired disease through blood transfusion was somewhat
higher than those who had acquired infection by other means. This observation
may have been the result of the more advanced age of such patients, as well

as their poorer general state of health.

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Certain prognostic factors of survival were noted in this study. Better
survival was associated with higher hemoglobin and performance (Karnofsky)
levels at enrollment, as well as the brevity of the period between the first
episode of PCP and the initiation of AZT therapy. These data point to the
importance of beginning therapy as soon as possible after the diagnosis of

AIDS or advanced ARC is made.

Although a great deal of information about the usefulness of AZT has been
gathered in a relatively short period of time, a very aggressive world-wide
program of clinical research is being mounted to address many as yet unanswered
questions. In the United States this program is being conducted in conjunction
with the AIDS Treatment and Evaluation Units (ATEUs). The largest group of
studies involves patients with different degrees of severity of HIV infection,
including patients with advanced disease (AIDS), milder forms of ARC, lymph-
adenopathy syndrome and even those who are infected but who do not have obvious
signs or symptoms of disease. Four studies, in fact, are being conducted in
this latter "asymptomatic" group, with the largest involving 1500 patients
randomized to receive one or two different dosing regimens of AZT or placebo,

A placebo-controlled study will also be conducted in otherwise normal indivi-
duals, primarily’ health care workers, who have been exposed, by cuts or
punctures, to HIV infected fluids. There is optimism that this approach may
be effective, because animal studies have indicated that administration of

AZT, if begun within a few days of challenge and continued only for a few
weeks, may completely prevent the establishment of retroviral infection
(38,40,42). In addition, the relatiyely brief period of therapy envisaged

is likely to produce few significant adverse reactions in healthy individuals.

Studies will also be conducted in special patient populations, such as hemo-
philiacs, intravenous drug abusers and children. Preliminary data from
children (6,34) indicate that their absorption, distribution, metabolism and
excretion of AZT is similar to those of adults (44), as are the benefits and
adverse reactions to the drug (6). Chronic interstitial pneumonia, common
in children with AIDS, but rare in adults, may also respond to AZT therapy
(2). Particularly striking improvements in neurologic function have been
noted in pediatric patients (6). Additional studies concerning the effect

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of AZT on abnormal neurologic function in HIV-infected adults will also be

conducted. Although significant improvements in neurologic function in adults
with AIDS and ARC have already been noted in controlled (15), as well as
uncontrolled (45), studies, additional research is required to precisely
define the degree of benefit and to further understand occasional neurologic
adverse experiences associated with the use of AZT (3, 11). Likewise, the
role of AZT in improving (19) or worsening (16,18) the thrombocytopenia often

seen in AIDS patients will be examined.

Other studies will examine different dosing regimens of AZT to determine
whether certain adverse reactions, particularly bone marrow suppression, can
be mollified while maintaining full therapeutic efficacy if smaller doses

are given, or if the dosing interval is lengthened. In addition, the use of
AZT in conjunction with a variety of other medications will be examined for
two distinct reasons. Certain drugs, such as acyclovir, ampligen, interferon,
and several others have been shown t) be synergistic in vitro with AZT in
inhibiting HIV replication (22,28-30,39) but additionai stuuies are required
to determine whether an additive or synergistic effect can be observed in
people. Additionally, some compounds such as GM-CSF and erythropoeitin may
counteract the marrow suppressive etfects of AZT (20). Some immunomodulators,
such as interleukin II, may enhance immune function at the same time that

AZT inhibits viral replication and such combinations are currently under
study. The combination of ribavirin and AZT will not be studied because
ribavirin has been shown to antagonize AZT's antiviral effect in vitro (43)

and in itself can cause anemia (13,24).

Studies will also be conducted to determine the safety and tolerance of A2T
when used in conjunction with drugs employed in the therapy of opportunistic
infections. Such medications include trimethoprim-sulfamethoxazole,
pyrimethamine and amphotericin B, as well as drugs to treat Mycobacterium
avium-intracellulare (MAI) infections (7). This latter study is particularly
important because MAI in itself produces bone marrow dysfunction (21) and
severely complicates and compromises the use of AZT in AIDS patients.
Anecdotal reports indicate that AZT induced marrow suppression is most severe

and less prone to spontaneous reversal in MAI infected patients (18). In

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addition, studies of the appropriate dosage adjustment in patients with renal
and/or hepatic failure will be included as part of an extensive post-marketing
surveillance program. Finally, intensive viral sensitivity studies will be
performed to determine the potential of resistance development. Although_
years may pass before the results of some of these studies enable us to have
& more complete knowledge of the full therapeutic profile of AZT,.sufficient
data already exist to indicate that it is a valuable weapon in the physicians.
armamentarium to improve and lengthen the life of patients with AIDS and

advanced ARC.

It should be emphasized that the rapidity and success observed in the develop-
ment of AZT as a treatment for AIDS and ARC is very atypical. The urgency

and fear generated by the threat of HIV infection in the United States has
fostered an atmosphere of extensive cooperation in identifying and developing
new agents for the treatment of the various stages of HIV infection, as well

as the numerous infections which complicate the infected patients’ course.

The spirit thus extant between certain individuals of the National Institutes

of Health and National Institute of Allergy and Infectious Diseases, researchers
and clinicians in those communities where HIV infection is prevalent, researchers
of the pharmaceutical industry, and certain members of the Food and Drug
Administration figured prominently in allowing the significant speed with

which AZT became available to large numbers of HIV infected patients. Whether
other promising agents become available in the marketplace with such rapidity
awaits to be seen. However, future endeavors will likewise necessitate
considerable cooperation among researchers in academia, industry and the

government.

Development of AZT is also unlikely to serve as a precedent for the development
-of other compounds found to be active against this virus in the test tube.

A historical review of drug development unfortunately reveals that the majority
of chemicals exhibiting in vitro activity never become useful drugs. Some

are simply not effective, either because the original test tube testing was
less than stringent or because conditions which allow virus proliferation

and its direct and indirect adverse effects in the human being are vastly
different from those in the test tube. Ascertaining the reliability of in

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vitro predictors of efficacy in humans becomes even more problematic when
dealing with immunomodulating agents because compounds which increase the
numbers or activity of immune cells may also merely increase the numbers or
susceptibility of cells available for viral infection. More commonly,
chemicals do not become drugs because unacceptable toxicity may be observed

in experimental animals or humans that was not or couid not be evident in
initial tissue culture assays. Finally a myriad of other factors, including
poor absorption following oral administration, rapid excretion, rapid meta-
bolism to an inactive compound, poor penecration into the CNS, or even the
inability to manufacture the material in large scale with consistent identity,
purity and potency all mitigate against successful drug development.

Drug development in general, and anti-AIDS drug development in particular,

is a labor- and money-intensive venture filled with many promising leads

which usually lead to failure and disappointment.- This general lack of success,
however, should not lead to cynicism or disillusionment with the entire process
but should evoke a nealtny scepcricism among patients.who are using a variety

of unproven nostrums. The drug development process requires a great deal of
knowledge, skill, time and luck to ensure that a compound is a safe and effec-
tive drug. The last thing any of us wishes is the widespread use of something
which proves to be, on subsequent careful examination, either useless, or

toxic or both.

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at The Wellcome International Antiviral Symposium. Monte-Carlo; December
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2. Bach, MC. Zidovudine for lymphocytic interstitial pneumonia associated
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3. Bach, MC. Possible drug interaction during therapy with azidothymidine
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4u,  Barre-Sinoussi, F, Chermann, JC, Rey, F, Nugeyre, MT, Chamaret, S,
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' Zidovudine in eight HIV-infected children for a 6-month period. Abstracted
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7. CDC. Diagnosis and management of Mycobacterial infection and disease
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8. CDC. Follow-up on Kaposi's sarcoma and Pneumocystis pneumonia. MMWR
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9. CDC. Kaposi's Sarcoma and Pneumocystis pneumonia among homosexual men-
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10. Chaisson, RE, Allain, JP, Leuther, M, Volberding, PA. Significant changes
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Gill, PS, Rarick, M, Brynes, RK, Causey, D, Loureiro, C and Levine, AM.
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Gottlieb, MS, Wolfe, PR and Chafey, S. Case report: Response of AIDS-
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Horsburgh, CR, Mason, UG, Farhi, DC, Iseman, MD. Disseminated infection
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Hartshorn, KL, Vogt, MW, Chou, TC, Blumberg, RS, Byington, R, Schooley,
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Lyerly, HK, Cohen, OJ and Weinhold, KJ. Transmission of HIV by antigen-
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Mitchell, WM, Montefiori, DC, Robinson, WE, Strayer, DR and Carter, WA.
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Mitsuya, H, Weinhold, KS, Furman, PA, St. Clair, MH, Lehrman, SN, Gallo,
RC, Bolognesi, D, Barry, DW and Broder, S. 3'-Azido-3'-deoxythymidine
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human T-cell lymphotropic virus type II1I/lymphadenopathy-associated

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The toxicity of azidothymidine (AZT) in the treatment of patients with
AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.
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Sharpe, AH, Jaenisch, R and Ruprecht RM. Retroviruses and mouse embryos:
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St. Clair, MH, Richards, CA, Spector, T, Weinhold, KJ, Miller, WH, Langlois,
AJ and Furman, PA. 3'-Azido-3'-deoxythymidine triphosphate as an inhibitor
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Tavares, L, Roneker, C, Johnston, K, Nusinoff-Lehrman, S and DeNoronha,
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Yarchoan, R, Klecker, RW, Weinhold, KJ, Markham, PD, Lyerly, HK, Durack,
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Presentation for Presidential Commission on the

Human Immunodeficiency Epidemic February 19, 1988

Developing a Drug: Ampligen - A Case Study
by William A. Carter, M.D. Chairman,

HEM Research

I am the Co-discoverer of Ampligen and have been the principal
catalyst in its development over the last several years. I will
briefly describe the environment in which Ampligen was discovered
and nurtured to its present state of development. Dr. Mollica,
Director, Pharmaceutical Research at E. I. DuPont, will describe
present efforts at large scale manufacturing and the breadth of
our jointly-sponsored nationwide clinical evaluation progran.

Dr. Lennox, principal investigator at one of our key
participating hospital sites, will overview some of the tedious
but very necessary tasks required to implement definitive studies

of promising anti HIV-agents at the clinical level.

Ampligen was discovered by Dr. Paul Ts’o and myself in the 1970’s
while at Johns Hopkins University. The conceptual background was
as follows: we were searching for a component common to various
human virus particles which would be capable of stimulating both
the body’s immunological defenses and the antiviral mechanism at
the single cell level. Earlier, work at Merck had suggested that

double-stranded RNAs had a broad range of potential therapeutic

 

 

 
 

 

activity in this regard, but the products they developed there

had unacceptable toxicity and low therapeutic ratios.
Accordingly, very little clinical progress was being made with
the primary required target of dsRNA-namely, untreatable human

cancers.

Double-helical RNAs actually look like two-winding staircases
which intertwine at a given frequency. I am sure you are all
familiar with the shape of double-helical DNA and RNA (or
Ampligen) is quite similar. The essence of our discovery was to
produce little out-pouchings, or mismatches, in the molecular
staircase which resulted in a dramatically different biological
effect - a fragile molecule which nonetheless triggers a
biochemical variety (termed "cascade") of host immune/antiviral
responses and then would undergo accelerated biodegradation -

hence its lack of any significant toxicity.

Ampligen is thus a type of artificial "virus", if you will, which
we initially developed primarily for treatment of human cancers.
and only later (1986) did we recognize its broad-spectrum anti-
HIV potential. Our earlier work in cancer was supported
primarily by the NIH and we are especially indebted to the NCI,
Dr. DeVita and his colleagues in the Division of Cancer Diagnosis
and Biology for being long term believers and supporters of the

scientific merit of Ampligen.

 

 
 

 

Thus, Ampligen was not an "overnight eureka" but rather a logical
scientific discovery after years of laboratory research with
concrete objectives. In the late 1970’s and early 1980’s, we
began to expand cautiously the therapeutic potential of Ampligen
by laboratory studies which suggested that many human viruses
might also be susceptible to its unique immune
enhancing/antiviral mechanism. This broad spectrum antiviral
feature of Ampligen may ultimately prove especially important in
people with HIV infection since often other viruses are isolated
in these individuals especially as. their immune statuses undergo
further deterioration over time. Ampligen is thus a powerful

probe of the potential role of other viruses in HIV-induced

disease progression.

The development program of Ampligen is a model one in that the
concept was developed initially in an academic environment.
Hahnemann University in Philadelphia, working with HEM Research,
was central to strengthening Ampligen’s scientific underpinnings
between 1980-1986 and I share with you here (a hardbound copy of
Ampligen scientific article reprints) the productivity for just
one 18 month interval. By 1986, a more entrepreneurial
environment was' necessary with the discovery of its anti HIV
activity and the realization that hundreds of individuals, as
opposed to dozens, would require evaluation before, during, and
after Ampligen treatment. The entrepreneurial environment led
ultimately to the HEM/Du Pont joint venture, the scope of which

will be addressed by Dr. Mollica. DuPont was already committed

 

 
 

 

greatly to AIDS research. But suffice it to say that the
intellectual freedom/entrepreneurial spirits still are "alive and
well" in this joint-venture; the opportunity for innovation in
manufacturing, clinical study design, etc. can flow from
cooperative efforts of a large and a small company just as well
as, and in some instances, superior to those of a purely academic

setting.

We believe that the integrity of this scientific/medical effort
to find an effective non-toxic HIV treatment cannot be short-cut.
Short cut processes include avoiding the rigorous process of peer
scientific review such as by going straight to the lay press with
interesting new findings or by avoiding FDA sanctioned clinical
studies. At the end of the day, such short cuts can only
compromise the care that HIV-infected individuals will receive.
Accordingly, we always first publish our data in recognized
scientific journals and, after publication, provide only limited
releases to the lay press which conform fully with both the
spirit and the guidelines set forth by the FDA. Where possible,
we try earnestly to present all data with a full biostatistical
analysis so that the reader can evaluate for himself, or herself,
the relative likelihood that the data will be reproducible
overtime. Suffice it to say that we have found that our recent
data (T4 cells, virus load, skin tests etc.) with 18 months
treatment experience in HIV treatment agree well with
interpretations from a 1 month experience reported in Lancet 1987

(June); accordingly, no patients, no families, and no physicians

 

 
 

Po

5

have been misled. Over 2000 patient study weeks data agree with
pilot data because quality assurance mechanisms were in place
both at the laboratory and clinical level from the beginning of

our work.

. We are acutely aware of the special needs of our patient
population and working towards an Ampligen treatment program
which will utilize community physicians in our research endeavors
and we are making every effort to provide treatment in AIDS/ARC
in non-hospital settings. Indeed, one of the great promises of
the preclinical work with Ampligen, is the suggestion of
Ampligen’s potential as "base biological" treatment, is that it
may increase the effectiveness of other anti-AIDS drugs. By
allowing .a reduction in dosage of potentially toxic, though
necessary, therapies, Ampligen may thus be able to reduce
dramatically the need for extensive hospitalization with its

devastating effect on personal finances and morale.

We have established a close scientific contact with the FDA and
especially the Bureau of Biologics within the agency has provided
invaluable assistance in the accelerated development of Ampligen.
Our own experience suggests a remarkable level of readiness on
the part of the FDA to assist all manufacturers, whether small or
large companies, in accelerating their clinical programs.
Accordingly, we find no basis, whatsoever, for the occasional FDA
*“bashing"™ on the grounds that the Agency is proceeding "too
..Slowly" to follow up possibly important therapeutic leads. To

 
 

 

the contrary, our concern is that pressure groups would cause
administrative/scientific disruptions within the FDA: such
changes, however, in the name of "progress" might only disrupt
very effective working teams within the agency and thus produce
new cadres which needed to get up on new "learning curves",
explore new ways to collaborate, etc. In summary, we feel the
agency is discharging its functions well and that regulatory
mechanisms are already in place to accelerate the work of all

manufacturers in the anti-HIV therapeutic arena.

As a senior scientist in the Ampligen development program, I am
very much involved in all aspects of clinical and laboratory
program. We are expanding our clinical programs as each month
passes and plan a series of scientific manuscripts which combine
rigorous laboratory and clinical data such as we published 8
months ago, in Lancet. At present, over 300 individuals (males)
are enrolled in our HIV-treatment programs and we intend to
include females as as an integral part of our future study plans.

We are trying, with cooperation of the FDA, to compress a process

which might normally require 8 years to, hopefully, 2 years.

In closing, all staff at HEM Research have made dramatic
commitments to Ampligen recognizing the magnitude of the epidemic
and the potential of our approach. This commitment, where our
staff commonly work 60-100 hours per week, has been the key to

our progress to date. A similar commitment has been made by

 

 
 

 

staff at E.I. DuPont and for further details I turn over to my

colleague, Dr. Mollica.

 

 
 

 

Testimony of Ted Lenox, M.D.

I am Ted Lenox, M.D., an Assistant Professor of Medicine at
New York Medical College at Valhalla, New York, and an attending
physician in Infectious Diseases at Metropolitan Hospital Center,
one of the city operated hospitals in New York City. I have been
asked to describe my experiences in establishing and running the
Ampligen trial at my hospital.

I was first approached with this project on November 2,
1987. By this time, the protocol had gone through the first of
three IRB’s needed to do research at Metropolitan. This is the
first major obstacle to doing any research at my hospital.
Because we are a medical school affiliate at a city hospital, we
must submit protocols to New York Medical College, then to the
Research Committee at Metropolitan, and finally to the Research
Office at Health and Hospitals Corporation (HHC) headquarters.
You can imagine how long this process can take. On a different
projgect, it once took six months just to approve the consent
form. Obviously, any revisions of the protocol must be
resubmitted through the same channels. Dr. Gary Wormser, the
chief of Infectious Diseases at New York Medical College and my
co-investigator, had submitted the protocol to the college and
had received approval after several amendments had been made and
about four months had passed. I then became responsible for
obtaining the necessary approvals from Metropolitan Hospital and
from HHC. JIn ten working days, I had received written approval
from the hospital and verbal] approval from HHC. However, the
‘written approval from HHC, which was necessary prior to enrolling
clients, did not come until] Dec. 10, almost a month later. 1

must sav that this is an unusually short period of time and it is

 

 
 

 

indicative of ‘the recognition of the importance of this
particular protocol.

During this process, the second obstacle was to find the
personnel to coordinate and essentially run the study. I was
fortunate to know a registered nurse who has excellent:
qualifications and was interested. He has worked as a medical
technologist, a lab supervisor in a major NYC hospital, and has
counselled extensively for GMHC. He was hired quickly and
recommended the second nurse who was hired. From previous
experiences, finding qualified, interesled personne] is not easy.

The nurses are primarily responsible for the day-to-day
functioning of the study. They answer the telephone, screen
clients and answer their questions, do the scheduling, draw the
bloods, supervise other required tests, administer the infusions,
and are ultimately responsible for collecting the data. I have
with me one of three notebooks which we are required to keep on
each client. The paperwork is phenomena]. The data is
originally entered into a workbook and then has to be transposed
into the more permanent case reporting forms. We have been told
that the workbooks must be kept as the primary source of the
data. We would like to hire an additional person just to handle
the paperwork.

Counselling skills have been an invaluable asset in working
with our clients, most of whom are still healthy and working
daily. Because of this, many have been able to minimize the fact
that they are HIV positive. Once they enter the trial] they are

reminded at least twice weekly that there is a real possibility
cf deterioration and they must face the idea of their own demise.

One client reported nightmares for several nights prior to his

noo

 

 
 

 

first unfusion; they since have ceased. Other clients are
extremely anxious and a calming force is important for them and
for us if we hope to keep them in the study for nine ponths. The
level of their anxiety is frequently heightened once they have
entered the study.

A major obstacle was finding available space at the
hospital, and this is still not entirely settled. Space is a
premium at Metropolitan and we must compete with pre-existing
clinics who need additional time and space. The space which had
been allocated for us was Jater cut in half. The space which was
promised by early January is still not completed and we are
operating primarily out of my office which is also used by two
infectious disease fellows. A more recent problem arose when we
attempted to instal] telephone lines to support the printer to
receive lab reports and the fax machine to receive the
randomization data from Dufont. The city bureaucracy was in ful)
force here. It took three weeks just to get the administrative
approval to instal] the telephcne lines. When we went to hook up
the fax machine last week, the line was dead. To get someone to
look at it requires a work order and the promise that "We’ll get
to it soon." We were informed on Tuesday, that because of
construction in that area of the hospital, the electricity may be
turned off for two weeks. Therefore in order to get the data we
need to evaluate our clients we would have to phone directly.
However, in order to do that we must request permission from my
Department Office for each phone call, including collect calls.
This can be a time consuming venture.

The next problem came with the recruitment of clients. AS

my own patient population is primarily IVDA’s, we had to recruit

 

 
 

 

from outside our own population. I wrote letters to all of the
local] infectious disease attendings and used lists of resources
published for PWA’s and PWArc’s and wrote to appropriate groups.
Most of our referrals have come from private physicians. Several
organizations have called us regarding the eligibility criteria
and have promised to refer clients to us.

As of this morning, we have taken a minimum of 120 telephone
calls, begun or completed active screening on 28 clients,
eliminated 12, and have begun infusions for five with three more
planned to begin next weeh. The total number of calls taken is
misleading because a great deal] of time can be spent counselling
clients, some of whom decide to enter. Many calls request
information or the clients are disqualified very quickly, e.g.
women or IVDA’s and have not been counted. Clients have decided
not to enter for mostly three reasons: 1]. an unwillingness to
tahe a chance with a placebo; 2. an unwillingness to stop PCP
prophylaxis or antiviral or immunomodulating agents several of
which are used frequently in New York; or 3. the rigorous demands
of the study, i.e. twice weekly infusions for nine months.

In conclusion, doing a research trial like this in a setting
such as mine is full of frustration and disappointment and a lot
of long hours. I have taken on this resposibility in addition to
py clinical, teaching, and administrative duties with assistance
from my colleagues in my division. My staff and I are encouraged
at this early date by the very positive, appreciative response
which we have received from our clients. We must never lose
sight of the number of lives already lost to this epidemic and
use whatever resources avallable to get effective therapy to as

many people as possisble. We should never allow ourselves the

 

 
TT

complacency of designing trials because that’s the way it has
been done before. We must continue to question whether it is
still ethical to run placebo trials and when must we stop denying
clients adjunctive therapy which may be beneficial. Must we .
define an endpoint as one in which the patient becomes seriously

il] and accept the loss of lives as necessary?

I would recommend the following:
-that counselling support for the clients as well as the staff
become a part of future research projects. All involved need
emotional support to complete a long study

-~an up-to-date clearing house for dissemination of available

 

trials with information regarding the protocol eligibility
requirements. I am aware that some are available, but these
frequently have old or incorrect information.

-incentives to public institutions to encourage the
development and implementation of research projects.

~the involvement of private physicians to assist in the
development and implementation of research projects

-the inclusion of all persons at risk in future trials.

-~the redefinition of endpoints to eliminate the necessity of

expecting serious illness or further loss of lives.

 
 

 

Testimony of Joseph Sonnabend, M.D.

My name is Joseph Sonnabend. I am a physician and have been
providing primary care for people with Aids since the beginnings

of this epidemic.

I am grateful to have this opportunity to tell you about the
Community Research Innitiative. Of the many emergencies that
comprise the Aids crisis, the need to rapidly develop effective
treatments is perhaps the most pressing. This means that we have
to expiditiously test many different treatments and combinations
of treatments simultaneously. This requires access to a large
population of individuals with AIDS and AIDS Related Conditions,
as well as an appropriate administrative structure that would
insure the proper conduct of trials and the efficient gathering

and analysis of data.

The Community Research Innitiative can fulfill both these
requirements. Community based trials can tap into the large
population of People With Aids who are seen in the practices of
communtity physicians. These patients are ina relationship of
trust with their physicians who are eager to participate in
treatment research. Secause this group of patients are largely
white gay men the CRI is committed to actively reaching groups of
patients who are under-represented in these practices. At its
second meeting almost a year ago the CRI's Institutional Review
Board addressed the issue of equitable entrance into treatment

trials for all people with AIDS. I believe this kind of

 

 
 

responsiveness indicatas an important advantage a community based
research endeavor has in comparison with Medical Center based
research. One only has to took at the demographics of the large
multicenter AZT trial to see this contrast. There were virtually
no women nor black men who were enrolled at any of the study

centers.

As a community based organization sponsored by People With AIDS,
the CRI is particularly sensitive to their needs. The importance
given to the issue of equitable entrance is not the only example.
The issue of pneumocystis pneumonia prophylaxis and the use of
placebos in critically ill individuals are two further examples.
Pneumocystis pneuemonisa is the most frequently occuring
opportunistic infection in AIDS. This infecton is almost
definately preventable although the kind of data that is needed
to provide proof of efficacy has yet to be obtained. It is of
course of great importance to systematically gather such data and
provide proof of efficacy. It is also important that People With
AIDS are not denied access to an intervention that will most
probably prevent pneumocystis pneumonia while trials establishing
efficacy are underway. The CRI is meeting both of these needs. A
200 person formal trial of aerosolized pentamadine for the
prevention of pneumocystis pneumonia has been underway since the
beginning of January at the CRI. Data obtained from this study
which will last for a year will add to data gained from similar
studies at the San Fransisco General Hospital in providing

evidence regarding efficacy and longer term safety. At the same

 

2

 

 

 
 

eee

time as conducting a systematic study on PCP prevention, the CRI,
in considering other trials in AIOS patients requires that PCP
prophylaxis ts not denied to trial participants. Of course this
means that the occurance of PCP can no longer be an end point
when testing-.a particular AIDS treatment. The studies are
therefore more difficult but certainly not impossible to design.
I should also point out that the move towards PCP prevention has
originated in the community of People With AIDS. It is largely
in response to pressure from this community that the use of a
life-saving intervention is now being offered to more
individuals. The CRI has also shown that the wider availability
of such an interventiuon is not incompatable with the systimatic

gathering of data that is required to obtain proof of efficacy.

On the issue of placebo controll trials, the CRI is also

responsive to the community of People With AIDS in resisting the

 

use of placebos in trials where the life expectancy of the
individual may be shorter than the duration of the.,trial. Of
course there are places for placebo controlled trials but
critical illness with a short life expectancy is not one of them.
There are other ways to conduct controlled trials that do not
require the use of a placebo. For example, the CRI is about to
begin a blinded trial comparing two dosages of active lipids

analogous to AL-~-721.

There is a further advantage that community based trials offer in

comparison with those conducted in medical centers. This relates

to the fact that People With AIDS who are trial participants are

 

 
 

 

7

Since this would exclude them from entrance into the trial, these

now taking a number of interventions on their own innitiative.

individuals are witholding this information. CRI trials are more
likely to acknowledge this reality and design studies that wil]
take this into account. Of course there will be some studies in
which the use of specific treatments outside a particular

protocol would make it impossible to interpret the results.

The conduct of trials outside medical centers is novel but not
unprecidentad. I founded the AIDS Medical Foundation with Dr.
Mathilde Krimm and one of our tasks was to conduct the kind of
community based research that the CRI is undertaking. Our
experience in establishing an Institutional Review Soard and in
approving and sponsoring trials in a communty setting indicates
that such trials can be successfully conducted. In fact many of
the CRI IR& members were also members of the AIDS Medical
Foundation IR& and thus have experience in reviewing community

based trials.

I'd like to end on a personal note. I am a microbiologist and
until 1978 most of my profesional life had been spent in the
rsearch laboratory with some clinical experience limited to
infectious diseases in a hospital setting. It is from this
background that I started to see patients in a private practice
in Greenwich Village in NYC. Many of these patients were gay men
who already had a variety of hemotologic abnormalities which in

retrospect were the earliest manifestations of AIOS. Thus I have

 

 

 
 

 

had the opportunity .to observe this epidemic from its onset. My

views on AIOS have been shaped by this considerable practical
experience and my rasearch background. I believe that the cause
or causes of AIDS remain unknown. The premature acceptance that
HIV1 and now HIV2 cause AIDS has resulted in almost all resources
being devoted to developing anti-retroviral treatments. The CRI
js less likely to be constrained by such a limitation. The years
since 1981 have been immeasurably bleak for us all. For all the
above reasons, I believe that the CRI represents a very
significant hope for the future and deserves all the help and

support it can gast recelye.,

 

 
 

 

 

AIDS
TREATMENT

INEWS

 

AIDS Treatment Access:
A Wish List, Some Problems, and Recommendations

Testimony of John S. James
Editor and Publisher, AIDS Treatment News

 

Before the Presidential Commission On the HIV Epidemic
New York City, New York, February 20, 1988

The biweekly newsletter AIDS Treatment News began as
volunteer research and writing for an AIDS archiving
organization in San Francisco. In little over a year it has
grown to a circulation of over 3,500 almost entirely by word
of mouth--an unexpected public response which illustrates the
critical dearth of practical treatment information felt by
patients and physicians alike. Researching treatment
articles for AIDS Treatment News has provided an unusual
opportunity to hear what this community would like to see
happen, and where it sees the obstacles now.

 

 

People react to an AIDS diagnosis in different ways. Some
resign themselves to dying and begin to prepare for death.
Others ask their doctors to make the medical decisions for
them, without their personal involvement. I do not have
contact with these people and do not know how they feel about
treatment research and access issues.

But very many persons with AIDS or other HIV infections

do choose to involve themselves in decisions about their
health care. They often become experts in the disease and
potential treatments.

And most of these people come to feel abandoned and betrayed
by society. They believe that many physicians, researchers,
and officials have been quick to write them off as already
all but dead--despite all the unknowns about this disease
which make it impossible for anyone to be sure that death is

 

 
 

 

inevitable. The projected deaths of at least a quarter of a
million Americans seem to have been accepted with surprising
equanimity and surprisingly little sense of crisis or
mobilization.

Oddly enough there seems to have been no professionally
conducted survey asking the persons most directly affected by
AIDS what they though about the issues of treatment research
and access now before this Commission. Certainly the people
I know have never been asked how they see the situation, what
problems they find in the institutional response to the
epidemic, and what improvements they would suggest.

A Wish List

Since we have no scientific survey information on what people
with AIDS would most like to see done, we did the next best
thing and interviewed Nathaniel Pier M.D., a physician with a
large AIDS practice in New York City. We have found his
statements about what is needed to be as close as anyone's to
the beliefs of the persons with AIDS with whom we have
communicated while writing AIDS Treatment News.

Dr. Pier proposed above all "That anybody diagnosed with HIV-
related disease or immunodeficiency be given a full
assessment of their situation and be allowed to choose to
receive a therapeutic regimen or decline it. Theoretically,
all five hundred thousand persons infected in New York should
be allowed access to some form of therapy if they wished. To
satisfy scientific needs, they could be enrolled in formal
protocols. Otherwise clinicians should be allowed to use
empirical regimens, with patients properly monitored.

"This way everybody would be given the optimal chance to save
their lives and nobody would be allowed to twist in the wind.
Furthermore, we could look at the results--and get a sense of
what works much more rapidly than under the current system.

"Persons could use single drug treatments, or rational
combinations based on the best judgment of experienced
physicians.

"What we propose here is what is already done with cancer
patients. Almost no one diagnosed in the United States today
with cancer is denied an opportunity to participate in
potentially lifesaving therapy. There is in place a widely
accepted system for providing these experimental and
established therapies to cancer patients. This system
advances our knowledge of the treatments for this disease but
is also a humane and compassionate way of caring for
patients.

 

 
 

 

"To the argument that there are no AIDS treatments except AZT
because no others have proven effective, we would answer that
we are currently capable of choosing safe, rational
approaches to therapies. In addition, people are using
therapies anyway. Our proposal would allow them to do so
under supervision, so this can be done safely and the data
developed can be critically evaluated and thereby be helpful
to others instead of remaining anecdotal."

Some Problems (See Lentinan Correspondence, Attached)

"It is clear that the best hope for people with immune
deficiency or at risk for the illness is the rapid
development and dissemination of safe and effective
therapies. Until this goal is achieved, the most humane
approach to dealing with AIDS and AIDS-related problems is to
give people access to supervised therapeutic protocols. The
main problem, therefore, is to develop such a system--a
system that would allow rigorous scientific analysis of
therapies and still incorporate anyone wishing to try to help
themselves with experimental therapies.

"The present system for developing AIDS therapies has been
painfully slow in starting. Access is so severely limited
that the majority of people affected by this disorder are

left without intelligent recourse.

"In addition it is unclear where the leadership for
determining priorities in therapy development is coming from.
It is also unclear how the decisions for prioritizing the
various therapeutic approaches are being made. For people
with AIDS it is unclear who is setting the timetable and who
is supervising the large-scale effort to develop therapies.

"For the individual who must make decisions there is no
centralized method of gaining access to the information that
will allow him or her to choose the best course of action.

“How does the present system work? As an example, we submit
correspondence relating to a potential therapy for AIDS which
first was recognized in 1984. In spite of prominent AIDS
researchers acknowledging the potential benefit of this
therapy, no clinical trials on humans with HIV infection have
been initiated since then. In addition, you will see that
letters to the people vested with protecting the public
health have gone ignored and unanswered. This has left the
impression that they are inefficiently and callously dealing.
with this very important issue. We do not believe that this
is truly the case. Nevertheless the letters have gone
unanswered and the trials have not materialized."

-3-

 

 

 
 

 

Other Concerns

Lentinan. Dr. Pier's statement above concerns his two-year
attempt to get this drug considered. We should point out
that lentinan has long been used for cancer treatment in
Japan, with complete safety. And a letter to The Lancet in
October 20 (attached), signed by seven scientists including
Robert Gallo M.D. describes its use in the successful
treatment of two patients which retroviral infections (on
with HIV, the other with HTLV-II).

In four years nothing has been done. Examination of Dr.
Pier's correspondence with governmental authorities clearly
illustrates the frustration and difficulty he experienced in
attempting to get this potential treatment considered on its
merits. Now we have heard that NIH has put lentinan into its
highest priority category for investigation--without ma jOr
new information, essentially on the basis of what was known
four years ago. However the drug-selection process is secret
so we only have hearsay and have not been able to confirm
that lentinan has been placed into the high priority
category, or that it was done without new information.

AL 721. The unhappy story of the repeated failures to test
this drug properly and make benefits available is presented
at length in the back issues of AIDS Treatment News,
submitted into the record of this hearing.

We would add two points not covered in the newsletter:

(1) We have heard reliable information that AL 721 was used
to treat one person with AIDS or ARC even before it was
submitted to Robert Gallo's lab for the successful in vitro
test against HIV replication published in the New England
Journal of Medicine, November 1985. In other words there was
one successful human test by early to mid 1985, a fact never
publicly revealed until this testimony. The public was
denied access to this information--compelling enough to some
for them to get Robert Gallo involved in further testing--in
the middle of a deadly epidemic.

 

(2) In yesterday's hearings one of the Commissioners asked
FDA Commissioner Dr. Frank E. Young if a therapy might be
developed to help overcome drug abuse, which is becoming so
important in the spread of AIDS. AL 721 was in fact first
developed primarily for that purpose. Theory, laboratory,
and animal studies have suggested that it might be effective
in reducing the symptoms of opiate or alcohol withdrawal,
thus helping abusers to overcome their habits permanently.
However to our knowledge no human study has been done--not

~4-

 

 
 

even a small, quick, inexpensive pilot study which would give
some sense of whether it was worth proceeding with this
potential medical intervention against drug abuse.

Trimetrexate. The important news about the approval of the
first AIDS-related treatment IND has failed to acknowledge a
major concern. Theory and laboratory studies suggest that
the trimetrexate with leucovorin therapy now, approved for
pneumocystis pneumonia (when standard therapies have failed)
would very likely also work against cryptosporidiosis, a
severe and often fatal diarrheal illness of persons with
AIDS. Cryptosporidiosis presently has no satisfactory
treatment.

We have heard that even a leading gastroenterologist has been
unable to obtain trimetrexate for compassionate use for
treating cryptosporidiosis. We have also learned that the
manufacturer, Parke Davis/Warner Lambert, has no plans to
develop the drug for this condition.

The result is that this drug, already proven so safe in
persons with AIDS that almost none of the (pneumocystis)
patients had to have the therapy terminated, will never be
tested for cryptosporidiosis under the current system,
despite the immense benefit the discovery of a successful
therapy for this opportunistic infection might bring.

Salk Polio Vaccine. The "old" Salk killed-virus polio
vaccine (not to be confused with Salk's current work on an
HIV vaccine) has recently been tried as a possible ARC or
AIDS treatment. Although it is far too early to be sure it
is effective, this therapy has generated considerable
excitement among the physicians who have seen the results.
In addition, according to an overview article which appeared
in The Wall Street Journal on January 27, 1988, this possible
therapy has also attracted unusual attention from some NIH
scientists, who have determined that persons receiving
repeated treatments with this vaccine have produced
neutralizing antibodies against the AIDS virus. We have
heard that Dr. Pitts is now collaborating with a university
and a county board of health on a formal study, approved by
his IRB--but that Dr. Pitts and a colleague must pay for the
vaccine out of their own pockets.

We have also heard two reports that Connaught Laboratories
Inc., the only company able to sell the Salk polio vaccine in
the United States, has recently made it difficult for
physicians to obtain supplies for use in treating AIDS--even
though it is perfectly legal for physicians to use it for
that purpose. One internist told us that. the company refused
to ship the vaccine unless he signed an affidavit that it
would only be used to immunize against polio. And we also

-5-

 

 
 

 

heard that Dr. Pitts' group had to threaten a lawsuit in
order to obtain supplies for the study cited above.

We have been unable to confirm these reports because
Connaught has refused to discuss them.

It is widely believed in the AIDS community that companies do
not on their own resist the development of new markets for
their products. It is generally presumed that these cases
reflect fear by the company of making enemies at the FDA,
which may fear damage to the regulatory process from the
development of a public demand for a drug outside of normal
channels. Bureaucratic interests may be best served if the
usefulness of a valid AIDS treatment is never discovered in
the first place. Patients' interests differ. All this in
conjecture, of course, as in these cases no one talks, and
unless an insider reveals information nothing can be proved.

The polio-vaccine case is not at all unusual. In case after
case, too numerous to list here, deliberate roadblocks and
obstacles have impeded patients in obtaining treatments, and
prevented research which could serve as early pilot studies
to indicate whether or not an idea deserved further, more
formal trials.

Recommendations

1. That either the Commission or another body investigate the
problems cited above, and dozens of similar ones which we can
bring forward, to find out what did happen, if there are
indeed roadblocks to treatment and treatment research, and
how these roadblocks could be overcome.

2. That the Commission arrange for a survey to ask persons
with AIDS, ARC, and asymptomatic HIV infection what they
think about current public policies regarding the epidemic,
and how those policies might be improved.

3. That the Commission ask the FDA to provide guidelines to
researchers outlining what studies would be required to
qualify a drug for treatment IND or for approval. These
guidelines should specify when it is and is not ethical to
use placebos in persons with life-threatening disease, or to
withhold use of previously proven therapies such as
pneumocystis prophylaxis.

4. That the Commission recommend the creation of a public,
computerized and printed registry of all human trials for
treating AIDS and related disorders should be established.
This registry should include pertinent information about each
drug, and the protocols, in language that can be understood
by a lay person. Registration in this database should be
required for all government-funded protocols, and voluntary

-6-

 

 
 

 

registry of all others should be encouraged.

5. That the Commission recommend steps to make access to
therapeutic trials equally available to all qualified
persons. A system must be established for insuring fair
access to everyone in need. A lottery might be suggested.

6. That the Commission suggest the creation of a
confidential, voluntary registry of individuals affected by
AIDS and related disorders, whereby these individuals can be
notified automatically when there are new trials for which
they can qualify. (This system could also help researchers
recruit for their trials.)

7. That the Commission recommend the immediate expansion of
funding for experimental trials organized and run at the
community level, using the resources of private and community
physicians, such as the Community Research Initiative in New
York, and the Community Consortium in San Francisco.

8. That the Commission encourage the current attempts to
share and disseminate reagents, materials, and scientific
data within the scientific community, to speed the discovery
of safe and effective therapies for AIDS.

9. That the Commission recommend the development of a system
such as compulsory licensing which would prevent proprietary
restrictions on data and access to drugs from impeding
development of AIDS treatments.

10. We urge the Commission to recommend that individual
patients and their physicians be allowed to choose to use
safe experimental therapies under supervision, even before
efficacy has been confirmed, if informed consent is obtained.

 

 
 

 

Testimony of John Scafuti

TEXT OF RECOMMENDATIONS PRESENTED BY JOHN SCAFUTI BEFORE
THE PRESIDENTIAL COMMISSION ON THE HUMAN IMMUNODEFICIENCY
VIRUS EPIDEMIC — FEBRUARY 20, 1988

Representing: Home Health Care Services, Inc. -— Research
Division, Aids Coalition Endowment (ACE), Aid Orlando,
Florida Task Force (FIF), University of Central Florida
Task Force on Aids, Orlando Gay Commmnity Services (GCS)

My testimony is dedicated to the memories of three particularly
motivated men who have preceded me here - Tom Jefferson, Patrick
Haney, and Jim Sammone - they have all expired within the last
two months, highlighting the urgency of our task.

I will present two sets of recommendations for expediting delivery of
unauthorized or investigational new drugs at the earliest possible tine.
The first set of suggestions are made within the current framework of

the drug approval system. I estimate this method of proceeding to be
only half as effective as the second more comprehensive set.

Under the new regulations governing IND compassionate use treatments
and IND protocols, a specific example is cited on page 19467, colum two,
next to the last paragraph, qualifying all stages of HIV infection as
"immediately life—threatened", thereby clearing the way for even the
asymptomatic patients to receive the most advanced treatments as soon
as possible. With as many as 2,000,000 potential clinical subjects there
should be no problems filling clinical trials - a requirement for
consideration of IND compassionate use treatments.

In most of the current trials in progress clinical subjects are
recruited from the most financially secure, and most pharmaceutical]
sophisticated patients. Both the FDA and the pharmaceutical companies
fail to address the implications of this reality. These patients are
much more likely to follow through with the full tem of the trial but
are not nearly as likely to adhere to the conditions of the trial.
This results in a smaller subject population but questionable validity.

A far more fertile source of clinical subjects is in the very clinics
where current care is significantly inferior - VA hospitals (See Enclosure
#2)"and free government clinics. This would offer some hope of advanced
treatments to the underprivileged that doem't now exist. While the popu-
lations in the trials would have to be expanded to allow for a higher
dropout, the trials would be far more valid due to closer adherence to
the testing conditions. There will be charges of bias against the under-
privileged and of using them as guinea pigs. The truth is that their
care will be significantly improved, they will enjoy a sense of contri-
bution to society, and the financial burden for much of their care will
be shifted to the private sector (the pharmaceutical companies). The test
results whould be far more valid due to closer adherence to the conditions
of the trial. In short, the positives far outweigh the negatives, regard-
less of the potential criticism.

 

 
 

 

~2-

RECOMMENDATIONS BY JOHN SCAFUTI (CONT'D) - FEB. 20, 1988

Under the new FDA regulations for IND compassionate use treatment
protocols, asurprising possibility has emerged. By the time a drug
has neared the end of Phase II (small controlled studies) and the
four general criteria have been met allowing IND treatments to begin,
there may be more liability to the physician, pharmaceutical company,
and the FDA for not providing the drug than that which is associated
with providing it. An interesting historical fact is that only one
case has been tried where an investigational new drug was administered.
The decision in all of the courts was consistently for the defendants.
What this indicates is that early usage of promising new drugs for
AIDS is likely to be rather non-litigious, while delaying usage,
conversely, could attract significant class-action litigation (2,000,000
Americans with HIV infection currently qualify as "inmediately life-
threatened") .

Two major defects in the IND treatment approach could, and probably
will, nix the whole system. While the FDA seems to be bending over
backwards to provide promising drugs at the earliest possible time,
the pharmaceutical companies are not compelled to provide the drugs
and the third party payors (Medicare, Medicaid, and private insurance)
are not compelled to pay for the drugs. Historically the FDA has played
a passive role. Even if they are now inclined to be more proactive, it
will be some time before they will be capable of making that adjustment.

To make the system work the government must put the public interests
of the ravaged populations above the proprietary interests of the pharma-
ceutical companies. ‘The appropriate legislation accomplishing this mst
be enacted. Part of that same legislation should include a requirement
that third party payors must pay for all IND treatment situations.
Without this legislation the new FDA regulations are clearly worthless
with only the very wealthy having any early opportunity to use expensive
investigational new drugs such as Ampligen.

The next set of recommendations fall outside of the current health care
and drug approval systems. Do not pursue a Manhatten Project for AIDS -
the historical Manhatten Project had a narrow well-defined purpose. The
scope and implications of this disease are far too broad and comprehensive
to be dealt with in the same manner. Such a project would likely be biased
towards strictly HIV theory, be focused on "magic bullets" rather than
disease control, and would not adequately address multifactorial possibilties.

 

 
 

-3-

RECOMMENDATIONS BY JOHN SCAFUTI (CONT'D) - FEB. 20, 1988

Instead of the Manhatten Project the Congress or the President
should literally DECLARE WAR ON AIDS and appoint "Joint Chiefs of Staff"
under the Department of Health. This body should have the same power to
fight AIDS as its military counterpart during wartimes. Represented on
this committee should be: the Surgeon General, the Commissioner of the
FDA, the head of the NIH, the Conmissioner of Insurance, a representative
of the pharmaceutical industry, and the head of the Department of HRS.
Balancing the traditional government and bureaucratic bias in the compo-
sition just stated, it is essential that leaders of groups hardest hit
by this epidemic be well represented on this panel: homosexuals, Blacks,
hemophiliacs, and women. Since many of the anticipated decisions will be
economic and based upon questionable statistical data, it is essential
to include cost accountants and statisticians as well. At no time should
the private representation be outnumbered by the government representation.
A significant effort should be made to include HIV positive individuals
whenever possible. No one has a greater inherent human right to make
decisions affecting survival than those who are struggling personally
to survive. This body would formulate strategy, implement policies, and
serve as a board of appeal for conflicts which would inevitably arise.

Rather than trying to squelch the AIDS drug underground (those efforts
would be miserably unsuccessful, ill-advised, and a huge waste of time,
money, and energy); we should instead devise a strategy for gaining as much
information as possible from that system. We must provide physicians with
incentives to track and report the polypharmaceutical treatment strategies
which are being followed by their patients. Most experts agree that
ultimately a multifactorial approach consisting of combinations of anti-
virals, immune enhancers and immme modulators will effect the greatest
degree of disease control. Instead of fighting what is going to occur
anyway, we could gain valuable insights for controlled combinational
studies based upon subjective indications, which become apparent when the
data is reported in huge numbers by physicians throughout the country.

To create incentives for this project, I propose the following:
(1) Statisticians working with highly informed physicians and researchers
who have an understanding of the polypharmaceutical possibilities would
design computerized patient histories, regimens, baseline and maintenance
lab data in the most convenient fashion possible. (2) Participating physi-
cians should be given a prestigious labeling which could be recognized by
the general public in advertising media (example: NDI - "New Drug Investi-
gator"). (3) Provide participating physicians with the most sophisticated
interactive data retrieval system to date, enabling ¢hém to know inmediately
as evolutionary advances in treatment possibilities are occuring. Also
include a complete registry of all trials planned or in progress relative
to any AIDS issue. (4) The government should pay the physician for his
additional efforts on a per patient basis.

 

 
 

 

-4-

RECOMMENDATIONS BY JOHN SCAFUTI (CONT'D) - FEB. 20, 1988

The significance of creating the model described above cannot be
underestimated. While there are very few reports of drug interations,
there is no responsible tracking going on and extremely useful ‘combinations
may be going unnoticed. By expanding the subject population to enommous
proportions we can validly include a large number of variables and still
produce extremely valuable subjective indications for more controlled
research. This offers the opportunity of leap froging current step-by-step
traditional research.

These proposals are obviously not "business as usual." Imagine the
progress we could make if they are implemented! It is long past time to
drop a "business as usual" approach.

Several enclosures have been included which support the conclusions
reached above:

Enclosure #1 - Example of Child Thriving with Unauthorized Drugs
(with Exhibits 1A, - 1F).

Enclosure #2 - Example of Inferior Medical Care in VA Hospitals.

Enclosure #3 - Example of Results Using Drug Prior to Marketing
Approval - DHPG

 

 
 

 

SUMMARY OF RECOMMENDATIONS PRESENTED BY JOHN SCAFUTI BEFORE
THE PRESIDENTIAL COMMISSION ON THE HUMAN IMMUNODEFICIENCY
VIRUS EPIDEMIC - FEBRUARY 20, 1988

I. Recommendations Within Current Drug Approval and Research Framework

A.

B.

C.

Utilize 2,000,000 potential clinical subjects providing greater
purpose to their lives and more advanced medical care.

Current clinical subjects are too sophisticated, Jeapandizing

the validity of trials in progress.

Use the vaiiand other government sponsored clinics for ‘the primary
source of subjects thereby raising the standard of care and shifting
much of the cost to the private sector. These subjects will also
yield more valid results.

Actively push for early usage of drugs thereby avoiding significant
possibilities of class-action litigation (2,000,000 Americans -:
all HIV+ are classified as "inmediately 1ife-threatened" by the
new FDA regulations) .

Close the holes in the IND treatment system by:

1. Requiring pharmaceutical companies to provide;
2. Requiring third-party payors to pay.

II. Recommendations Outside of the Current Drug Approval and Research
Framework

A.

B.

Do not pursue a Manhatten Project. It is likely to be biased
towards HIV theory only and too narrow to include broader concepts
of disease control.
DECLARE WAR ON AIDS!
1. Appoint “Joint Chiefs of Staff" with representation from both
government and private sector - include HIV+s. They should:
a. Formulate strategies
b. Implement policies
c. Act as a board of appeal in disputes.
2. Utilize data created from individuals using polypharmacy.
a. Design model using input from staticians, physicians,
and researchers.
b. Make reporting simple but comprehensive.
c. Assign a prestigious label to physicians participating in
the reporting process.
ad. Provide participating physicians with an interactive data
retrieval system.
e. Provide a complete AIDS registry of trials in progress
and trials planned.
f. Pay the physician for his reporting efforts on a per
patient basis.

III. Enclosures Supporting Recommendations Above

 

 
 

THE PRESIDENT'S COMMISSION ON AIDS
TESTIMONY
by
DR. HERBERT R. SPIERS
Saturday, February 19, 1988

Mr. Chairman and distinguished members of The President's
Commission on Aids. Thank you for the opportunity of presenting
this testimony on behalf of ACT UP --The AIDS COALITION TO UNLEASH
POWER.

For us, AIDS is not only about health, it is about politics.
This is a connection many of you may find difficult to accept. I
first became aware of AIDS in the summer of 1981 when it was called
“gay cancer." I now realize that I made a fatal error in my
understanding then. I focused on the word ‘cancer’ and assumed
that this new and mysterious disease would be dealth with in the
game manner as Legionnaire's Disease, which is to say with great

“urgency from our medical establishments and the White House alike.

It was not. It was a politically unpopular illness and not until a
few courageous voices spoke out against the lackadaisical political
and medical response to the by then already epidemic proportion of
the disease did the true personal, social and cultural horror begin
to stir the national conscience. This historical context is the
framework by which we judge today's promises of fast-tracked drug
developments and redesigned systems for clinical trials.

It is from within this tradition of neglect--even though
~perhaps benign neglect--that we are compelled to make sense of the
fact that as of this moment a Person with AIDS has, in the entire
breadth of this nation, access to only ONE ATEU trial testing a
drug other than AZT, and at that there are only twenty-five slots
available. This historical context prompts us to ask embarrassing
and provocative questions. Is scientific methodology really the
only reason that as of February 5, 1988 83% of all people enrolled
in ATEU trials are on AZT? Are our scientific wits so dull that we
cannot find effective alternatives to cruel and self-defeating
double-blind placebo trials? Are woman, blacks, children,
Hispanics and drug users somehow innately unqualified for drug
trials--for they are woefully underrepresented in trials currently
underway? Is the NIH really committed to a world-wide search for
potential new drugs or is it too comfortably wedded to domestic
products? Why must drug companies retest potentially life-saving
drugs because the FDA fails to make its rules and regulations for
the design of acceptable protocols clear and comprehensible?

In making answer to these and other questions the politics of
drug development must be addressed. There is still a leadership
vacuum in the fight against AIDS. Despite the noble intentions of
political and bureaucratic functionaries, AIDS will remain a
controversial issue on the national agenda until the Chief
Executive of our country removes it from partisan and ideological

 

 
 

 

2///

politics by personal moral example and by bold leadership. We have
heen told that AIDS is the nation's number one health problem, yet

is four letter word was not once uttered in President Reagan's
State of the Union address last January. Is this the type of
example to set for his subordinates; does this demonstrate
commitment and concern? Can the President not hold publicly an
AIDS baby in his arms or avail himself of' a photo opportunity to
shake hands with a Person with AIDS to educate the public about
compassion and how this disease is really transmitted? Let's start
at the top; let's start with the role of the Chief Executive.
Recommend to this President and the next to become truly involved
in the fight against AIDS.

You know that the AIDs Treatment and Evaluation Program has
not been a resounding success. After 18 months not a single report
has been published. You've been told that it has been revamped and
redesigned, that new committees have been added to expedite the
testing of more and different drugs. Nothing could please us more
than to see that happen. But we've had experience with the ATEU
program first-hand and we know that if it is going to work it must,
one, include participation from community physicians and, two, must
win the confidence of the very people it seeks to recruit. This
means outreach to AIDS communities in culturally appropriate ways
such as designing clinical trials commensurate with nonwhite, non-
middle class values. It means alternatives to placebo trials. And
it means convincing people like Dr. Iris Long that genuine efforts
are being made.

ACT UP is singularly proud of Dr. Long. There is perhaps no
more informed person on drug treatments currently underway in this
country than she. What we have learned about the problems with the
ATEU program can be of use in preventing similar errors in the new
program. Not content with simply a critic's role, Dr. Long and
several other ACT UP people have undertaken a pilot project that
will serve as a prototype for a national effort. We are developing
our own data bank on drug treatments at all hospitals in the
Greater New York area. Physicians and PWAs need up-to-date
information about drugs and drug treatments and this information is
nowhere available. Certainly, the government's databases, PDQ and
CLINPROT are not the answer. In addition, ACT UP will demonstrate
the importance of a Central Registry of clinical trials for
researchers and physicians, another idea we strongly urge this
committee to take under advisement.

For many of us, perhaps for many of you as well, there is
still a mystery as to how drugs are selected for clinical trials by
the NIH. Successes or failures notwithstanding, it has never been
satisfactorily explained why AZT and not some other drug or drugs
were put on a fast track approval process by the NIH and the FDA.
Recent press reports once again testify to the inherent suspicion
on the part of our great medical establishments to substances
developed aboard. To ensure that domestic business considerations

ould never be allowed to impinge upon drug selections we urge the
creation of an Ombudsagency to examine the experience of other

 
 

 

3///

countries in the search for new drugs to he tested. "The real
problem," say Commissioner Young, “is where do you get the ideas

nd where do you get the compounds from? That's the major block."
.andate imagination and creative research through such an
Ombudsagency. To demystify the process of drug selection and to
inspire trust and confidence within the various AIDS communities we
make two recommendations: first, both the FDA and the NIH must make
greater efforts in providing timely and current information that is
organized and systematized. The above mentioned national database
is indispensable in this regard, as are monthly and weekly
publications and a National Hotline on drugs and treatments to
which physicians and PWAs can make reference. Second, structure
community physicians’ and PWAs" participation in all drug review
committees.

On Tuesday of this week, with not a little fanfare, the FDA
announced that trimetrexate had been approved under a Treatment
IND. Bravo. But questions remain as to liability and treatment
costs within a Treatment IND protocol, and, in spite of a two day
conference just this week, the regulations pertaining to Treatment
INDs remain murky, prompting a number of informed persons to wonder
whether pharmaceutical companies would indeed submit their drugs
for Treatment IND approval. You've heard some glowing reports from
the FDA Commissioner. Let's hope they come to fruition. But again
we have historical reasons for being more than a little skeptical.
Supposedly thousands of drugs have been examined, over forty are
"in-the-works" yet only AZT is approved. What is the status of

HPG, the only hope for people suffering from CMV infection: will

r will not the Commissioner approve its release, or must the
parent company put it back into trials causing further delay of the
only drug effective against CMV retinitis?

And who in the government is willing to take even a modicum of
responsibility for possible abuse of The Orphan Drug Act? The
government grants exclusive drug marketing rights to companies, yet
it refuses to monitor possible abuses of a federally created
monopoly. In 1984, pentamidine cost $24.95 a vial. It now costs
four times that amount. Who pays for this whopping increase?
Individuals, insurers and, in a variety of ways, taxpayers, that's
who. While the government granted a marketing monopoly to Lyphomed
for penatmidine, the FDA's Office of Orphan Products Development
says that it has no monitoring power. We all know too well the
astronomical cost of AZT, another Orphan Drug Act product. This
act was intended to induce companies to develop drugs that
otherwise would go undeveloped without forms of financial
assistance. A wise policy and within the tradition of Chrysler and
Lockheed bailouts. But has it become a government handout?

Perhaps it is time to consider a United States Drug Development
Corporation that would be self-financing and would treat drug
patents and marketing rights as part of the public commonwealth.

Time does not permit me to focus attention on other issues
*ith which we are concerned. For example, does the FDA's Informed
onsent Regulation (21CFR50) which requires informing patients of

 

 
 

 

4///

alternative therapies before signing them up for a trial mean
making them conversant with drugs and treatments being used in a

imited geographical area, or does it mean all drugs and treatments
used throughout the country? Obviously, the answer to this
question is of significant moral and legal importance.
Discrimination, housing and health care, education are all part of
the politics of AIDS. The National Leadership Coalition Against
AIDS, a group of business leaders, recently suggested a bill of
rights for Persons with AIDS and for seropositives. It's time has
certainly come and I commend their idea to you.

I wish to close with that with which I began. We the woman and
men of ACT UP are gadflies, the grassroots variety. That is why
this commission, the White House, Dr. Young at the FDA, Dr. Fauci
at the NIH, governors, mayors, representatives, counsel members,
senators, health commissioners, candidates, and many other
varieties of politicians and bureaucrats and their anointed
appointees, find us buzzing about. We are driven by the Politics
of AIDS and despite attempts to shoo us aside, to ignore us, spray
us with invectiside, and all other means to dispel unwanted pests,
or more accurately, those perceived to be pests, we will in the
tradition of political gadflies keep you honest by ACTing UP.

Recent rhetoric would have us believe that the epidemic is
over--at least here in the US. Tis a consummation devoutly to be
wished. Still, one cannot help but wonder if the very same people
who were so late in coming to the battle are now prematurely

alling it at an end? For many here present this morning, the full
effect of the politics of AIDS was brought home forcefully by the
death in one's arms of a lover or a son, or the diagnosis of
Kaposi's Sarcoma in oneself or in a friend. My mistake --the
mistake of those most effected by this disease-- was to remain
silent too long; quitta in the assumption that the health of the
body politic was above the ideological issues of partisan
politics. With our mouths closed we watched the deaths mount. In
high school, we were taught that the price of freedom is eternal
vigilance. Sad to say, in the Age of AIDS, many of us have learned
that in our democratic society the price of health is perpetual
pressure and an ever ready pair of vocal cords.

In fighting for the cause of human life, no price is too
high. And so, even though some contend that the epidemic is over
because, they believe, it has not entered the white middle-class,
heterosexual population, we will continue to bring pressure to hear
commensurate with the goal we are seeking: an end to AIDS, an end
to dying.

My testimony, then, is a kind of pressure, delivered before
you in the form of verbal pleading. We ask you to examine fairly,
carefully, critically all the testimony that you have heard and
received. Weigh it on the scale of scientific merit and reason;
but also measure it with the rule of your own personal integrity.
You will be making recommendations effecting who will or will not
suffer, who will or will not die.

 

 
 

 

S///

On this issue we cannot and will not ever be silent again.

ask that your officially sanctioned voices speak out with us.

Thank you.

We

 

 
 

 

Testimony for the Presidential Commission on the Human Immunodeficiency
Virus Epidemic

February 20, 1988

New York, NY

Elinor M. Levy, Ph.D.

Associate Professor of Microbiology
Boston University School of Medicine
Boston, MA 02118

Each year we learn a little more about the natural history of HIV
infections. We now know that following infection with HIV some individuals
develop AIDS within a year, while others remain without any symptoms for at
least 7 years. Similarly, we know that some individuals with Kaposi’s
sarcoma (KS) die within months of diagnosis, while others live longer than
6 years. At this point, however, we have little evidence to explain these
differences, and therefore are unable to advise the estimated 1-2 million
Americans infected with HIV how to maximize their longevity. Should they
change their habits, their diets, their attitudes? There is evidence that
suggests that each of these might influence progression of HIV related
diseases.

I will concentrate my remarks on nutrition as a possible cofactor in
HIV related disease. In general, malnutrition is associated with a
significantly impaired immune response. The immune response is also
sensitive to deficiencies and excesses of single nutritional elements, and
to the quantity and quality of fat intake. Nutrition can be shown to
affect susceptibility to a variety of infectious agents, and is implicated
in the development of cancer. I have been involved in a pilot study of men
with AIDS related diseases who have chosen to follow a macrobiotic regimen.
This includes a vegetarian diet, a healthy lifestyle, and a sense of hope
and control. The large majority report an improved in AIDS related
symptoms. Additionally, those in the group with KS also showed an increase
in their number of lymphocytes during the first 3 years after diagnosis,
and 6/19 of these men are alive greater than 3 years after diagnosis with
KS.

Research into nutrition as a cofactor for progression of HIV related
disease is difficult for several reasons, among them prevailing research
priorities, the complexity of study in this area, and_ certain
methodological problems. Research priorities have focused on finding a
cure and developing a vaccine, both worthwhile but still elusive goals.
Only recently has their been a shift to include education to prevent HIV
infection, and an interest by ADAMHA in the role of psychosocial factors,
including alcohol and drug abuse, in AIDS progression. The group we have
been studying is an example of the likely interrelationship between
nutritional, psychosocial, and behavioral choices. Studies must take into
account these interrelationships in order to interpret data correctly.
Additionally there are methodological problems in accurately assessing
nutritional status, particularly if absorption may be a problen.

I would recommend that the NIH foster more of an interest in
nutritional and other cofactors through the organization of small workshops
to bring together the multidisciplinary talents needed to work out design
and methodological issues, and by encouraging research through RFAs. I
would recommend that nutritional components be added onto ongoing "natural
history" studies, and/or that new studies focusing on psychosocial and

 

 
 

 

nutritional cofactors be encouraged, including those with an intervention
design. Finally, I would recommend that NIH create multidisciplinary
review committees to properly evaluate these grant applications.

At this time I cannot given an estimated cost for implementing these
recommendations, but suggest it would be a modest investment compared to
what could be saved in health care and social service costs if onset of
debilitating symptoms can be delayed or prevented. Although the state of
our knowledge about the factors predisposing to the progression of HIV
infection is not extensive, it is extremely likely that cofactors play an
important role. There is an urgent need for research in these areas, so
that accurate information can be used as a basis for more effective
treatment strategies and educating persons at risk.

 

 
 

 

Submitted by Peter Duesberg, Ph.D.

PROBLEMS WITH THE VIRUS-AIDS
HYPOTHESIS

@ All known viruses are biochemically active when they
cause disease (polio, hepatitis, etc.).
Paradoxically: HIV is inactive, latent, even in fatal cases
of AIDS--no more active in AIDS patients than in
asymptomatic carriers.

@ All known viruses, when pathogenic, infect and kill
more cells than the host can spare or replace.

Paradoxically: HIV actively infects <1 in 10,000
T- cells, even in fatal cases of AIDS.

@ All known viruses produce primary viral disease after
short latent periods of 1 to 2 months.
Viruses act quickly or not at all.

Paradoxically: HIV is said to cause AIDS only after a
peculiar latent period of 5 to 7 years.

 

 
 

 

° ° 7 ! an“
a! ‘ : -? aa) a : ZO
4

@ All known viruses cause disease in the absence of
or prior to immunity.
This is why vaccination works--the ultimate weapon
against viral disease.

Paradoxically: HIV is said to cause AIDS in the presence
of or after antiviral immunity.
Antiviral immunity is diagnosed by the "AIDS test”.

© Unlike all other cytocidal viruses, HIV is a retrovirus.
Retroviruses do not kill cells. On the contrary, they

depend on living cells to reproduce.
This is why retroviruses were the most plausible viral
carcinogens in President Nixon's "War on Cancer".

Paradoxically: The retrovirus called HIV is said to cause
AIDS by killing T-cells.

© No known virus discriminates between men and
women, nor between heterosexuals and
homosexuals.

Paradoxically: HIV shows an absolute preference (92%)
for men, even seven years into the AIDS epidemic.

 

 
 

 

Mm,

Mk —
LEIDER - 9

* 4

@ Koch's first postulate for identifying a causative
pathogen states that the pathogen must be present
in all cases of the disease.

Paradoxically: The CDC guidelines of September, 1987
stipulate that AIDS can be diagnosed in the absence
of all laboratory evidence for HIV. ri Os - y(t

~ - - o + > £ ‘ nN ° =_ (E
iN VA Ais e bok PW. SY Ds i! ag \

CONCLUSION:

Unless these problems can be resolved

HIV is not the cause of AIDS.

 

 
 

 

Se ca cal
Bar Psychologica
SE Ascoclation

Sea Advancing psychology as a science, a profession, and as a means of promoting human welfare

  
  

 

es

TESTIMONY OF
Thomas J. Coates, Ph.D.
Co-Director
CENTER FOR AIDS PREVENTION STUDIES (CAPS)
and
Associate Professor in the Division of General Internal Medicine
at the

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

on Behalf of

THE AMERICAN PSYCHOLOGICAL ASSOCIATION
before the
PRESIDENT’S COMMISSION ON THE HUMAN IMMUNODEFICIENCY VIRUS
on the Subject of
BEHAVIOR CHANGE AND AIDS RESEARCH

February 20,1988

Admiral James D. Watkins, Chair

1200 Seventeenth Street, NW
Washington, OC 20036
(202) 955-7600

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS--February 20, 1988--Please do not quote or cite without permission. Thanks!

Summary of Recommendations

1. Change the national priorities. It is essential to spend as much or more
money on AIDS prevention and intervention research as on biomedical
research.

2. Fund additional studies to describe the characteristics of those who have
changed in comparison to those who have found it difficult to change
behavior so that intervention programs can be aimed at groups who have
the potential to spread the infection to others or to be infected themselves.

3. The NIMH in collaboration with other relevant agencies, undertake a
controlled trial of the efficacy of community intervention programs in
reducing high risk behavior.

4, The National Institute of Mental Health, in collaboration with other
relevant agencies (e.g, the CDC, the National Institute on Drug Abuse)
support a coordinated set of studies aimed at programs with high risk
populations or avenues of intervention.

In each area, a minimum of 5 to 7 studies should be funded to reflect
national distribution. The investigators should be encouraged to request
funding for at least five years, and the best methods of science should be
employed to plan the studies and to evaluate outcomes, The studies should
be designed to shed light on basic behavioral processes as well as to develop
disseminable programs. The investigators should be brought together
semi-annually to plan their studies and share their results. The best place
to accomplish this research is within the NIMH, hopefully within the AIDS
Branch to be established there.

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS-February 20, 1888-Please do not quote or cite without permission. Thanks!

1 am Dr. Thomas J. Coates. I am Associate Professor in the Division of
General Internal Medicine at the University of California, San Francisco,
where I also Co-Direct the Center for AIDS Prevention Studies (CAPS). I
am also a member of the Medical Attending Staff at the UCSF Hospitals
and Clinics. In that capacity, I direct the Behavioral Medicine Unit, and
have considerable clinical experience in counseling persons who are
positive for HIV, and who have ARC and AIDS. These include males and
females with a variety of sexual orientations and from a variety of ethnic
backgrounds. Many have had to relinquish their jobs, their relationships,
and their life. ;

I testify here also representing the American Psychological Association.
APA'S involvement in AIDS stems from our membership's goal of
responding to this epidemic with sound public health measures--a response
that protects the public and ensures the mental health of persons infected
with the AIDS virus. APA's members include clinical providers whose
patients manifest the spectrum of HIV infection, from HIV positivity to
AIDS related complex (ARC) to frank AIDS. We also include among our
membership research scientists who are seeking effective means to
promote lasting behavior change; who are examining the impacts of HIV
antibody testing; and, who are analyzing the ramifications of AIDS for all
segments of the population. APA members also include educators who are
teaching the public about AIDS and safer sex, industrial psychologists who
are addressing the issues of AIDS in the workplace, psychologists .
providing counselling and other services in the schools and individuals
who are providing services both professionally and on a volunteer basis to
the hundreds of local community-based AIDS service provider
organizations across the country. Clearly, APA members are involved in
addressing this dreaded disease from a variety of perspectives.

As an organization, APA has taken steps to respond to this crisis since the
very earliest days of the epidemic. We have been at the forefront of lobbying
for AIDS appropriations. We have worked to keep mental health providers
aware of the unique aspects of this disease. In 1986, our Council of
Representatives adopted a resolution on AIDS which deplores
discrimination against those affected by the epidemic, condemns the use of
the epidemic as a vehicle for prejudice, opposes the indiscriminate use of
the antibody test, and calls for the confidentiality of patient records while
recognizing the need for "large-scale identification of AIDS seropositive
persons" as a major public health goal. At its most recent meeting in
February 1988, the Council adopted a second resolution urging speedy
action to incorporate information about AIDS and its transmission and
prevention in those elementary and secondary educational programs that
address human sexuality, drug use, and family issues.

In June 1987, APA established a Task Force on Psychology and AIDS that
will examine more closely the behavioral aspects of this disease and direct
the psychological response to the epidemic. In addition the Board of

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS-February 20, 1988-Please do not quote or cite without permission. Thanks!

Directors is currently considering a proposal to establish an Office on AIDS
with an operating budget of approximately $160,000. The activities projected
for this office include information dissemination to psychologists and the
general public, technical assistance to the APA membership, work with
other professional organizations to ensure an appropriate mental health
response to AIDS, and continued advocacy around mental health,
psychological and behavioral issues related to the epidemic.

In addition, APA has just received a $750,000 contract award from the
National Institute of Mental Health (NIMH) to train health and mental
health providers about the mental health aspects of AIDS over the next
three years. Under the program design, a core of faculty psychologists will
work with established community AIDS resource persons at sites across
the country to deliver mental health training in locations with currently
low levels of AIDS cases but high projections of HIV infection.

My testimony will focus largely on change in sexual behavior. Other
experts on this pane! will focus on IV drug using behavior.

The Center for AIDS Prevention Studies

The Center for AIDS Prevention Studies is a $13 million project funded in
large part by the National Institute of Mental Health and the National
Institute on Drug Abuse.. Specific projects within the Center are also
funded by the National Institute on Allergy and Infectious Diseases, the
Department of Defense, and the University of California. The Center is a
collaboration between the University of California (at San Francisco and
Berkeley), the San Francisco Department of Health, and the Bayview-
Hunters’ Point Foundation (a minority community service organization)
which some of you visited while you were in San Francisco. The Center
seeks to complete studies that will identify determinants of high risk
behavior in all of the various populations likely to be hit by AIDS. Our
ultimate goal is to develop and test programs designed to reduce risk of
HIV infection in these populations.

Prevention Is An Absolute Necessity

Prevention is the top priority for AIDS. The Centers for Disease Control
reports that over 50,000 persons have been diagnosed and reported with
AIDS in the US and Public Health Service estimates that 1.5 million
persons are infected with this deadly and awful virus. The primary
objective in our efforts to fight AIDS must be to prevent any more people
from becoming infected.

The majority of the population is not infected HIV, and even the majority of
high risk populations is not infected with HIV. Our greatest effort must be
directed toward programs and research to prevent any more of the

 

 
 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS--February 20, 1988-Please do not quote or cite without permission. Thanks!

population from becoming infected. Unfortunately, we are fighting the
AIDS epidemic in the same way that we fight most diseases. We pour
money into biomedical research to describe the virus, to develop cures for
those who are suffering its ravages, and in developing vaccines.

This research is laudable and the progress that is being made is
remarkable. However, the priorities are lopsided. The original
unamended PHS Budget Requests for AIDS, Fiscal Year 1988! requested
$412,365,000 for research (including only $28,326,000) to ADAMHA, and
only $101,164,000 for Prevention. One dollar in four was to be spent for
prevention when the most effective antidote to the spread of the AIDS
epidemic is behavior change. My first recommendation, therefore, is to
change the national priorities. It is essential to spend as much or more
money on AIDS prevention and intervention research as on biomedical
research,

We are fortunate in the spread of HIV that a relatively narrow set of
behaviors seem capable of spreading the virus from one person to another.
In the realm of sexual behavior, this includes anal or vaginal intercourse
with the exchange of semen or vaginal fluid. Oral sex with the exchange of
semen or vaginal secretions may also transmit the virus, albeit with a very
low rate of infectivity. From an intervention perspective, we are fortunate.
Campaigns to reduce the spread of AIDS can be focussed on one or few
behaviors. This should increase their efficacy.

Our Current Research: San Francisco and the US

Are we able to achieve the changes necessary to stop the spread of the
epidemic? Our experience in San Francisco shows us that we can.

Since 1984, we have been involved in studies funded by NIMH docunienting
changes in high risk behavior in the gay, bisexual, and heterosexual
populations in San Francisco. (We are now beginning studies among
adolescents, ethnic minority single individuals, and other high risk
groups). These studies have been carried out primarily with two large
groups recruited at the beginning of the epidemic; our total sample is
around 1600 men.

Both studies show remarkable results. Men in San Francisco--gay,
bisexual, and straight--have reduced their high risk behavior to a
remarkable degree. The amount and kinds of changes in high risk sexual
behavior among gay and bisexual men exceed anything documented to date
in the public health education field or literature. The AIDS Behavioral

 

1 United States General Accounting Office. AIDS Prevention: Views on the
Administration's Budget Proposals. Briefing Report to the Chairman, Subcommittee on
Labor, Health, and Human Services, Education and Related Agencies, Committee on
Appropriations, United States Senate, August 1987.

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS--February 20, 1988--Please do not quote or cite without permission. Thanks!

Research Study reported that only 7.2% practiced unprotected anal
intercourse with secondary partners in 1986. The San Francisco Men's
Health Study reported that only 5.8% of HIV negative, individuals practiced
this activity in 1985. Communication Technologies, a marketing firm
working for the SF AIDS Foundation, reported that only 6% of their sample
practiced this activity in 1986.In San Francisco, there is no new infection
among gay or bisexual men.

Second, these changes are being sustained, and this is something almost
unheard of in health behavior change. Cigarette smoking, the leading
cause of death and disability in the US today, has proven remarkably
resistant to change over the 24 years since Dr. Luther Terry published the
first Surgeon General's Report on Smoking and Health in 1964.

What About the National Scene?

I and my colleagues at the University of California, San Francisco, have
also just completed studies for the Office of Technology Assessment and the
Hudson Institute. The topic of this study was changes in sexual behavior
since the beginning of the AIDS epidemic. We completed an exhaustive
survey of all of the studies currently being done in the US and Canada with
regard to prevalence of high risk behavior and factors associated with
behavior change in all populations for which data are available: gay and
bisexual men, ethnic minorities, adolescents, and single heterosexuals.”

Evidence from a number of studies indicates that high risk behavior and
seroconversion continues to occur in a number of localities including New
York, Los Angeles, Washington DC and other places. Rates of syphilis
continue to be high in certain localities among gay and bisexual men and
among other high risk groups as well.

Why Do High Risk Individuals Continue To Practice High Risk Behavior?

One response upon hearing that gay and bisexual men and others are still
practicing unsafe sex is to label them (e.g, "addicted," “homicidal") or to
pass restrictive laws calling for conviction and incarceration. These
probably do more to satisfy lawmakers than to stem the tide of the epidemic.

A more rational and helpful approach calls for understanding better the
psychosocial determinants of high risk behavior and aiming educational
programs at these determinants. For example, we and others have found
several factors to be associated with continued high risk behavior. Among
these are

 

2 Colleagues in this research are Ron D. Stall PhD MPH, Colleen C. Hoff, Joseph A.
Catania PhD, and Mary Margaret Dolcini MA.

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS--February 20, 1988--Please do not quote or cite without permission, Thanks!

e those who use drug and alcohol use during sex are more likely to
engage in high risk behavior

¢ men who are younger in age are more likely to engage in high risk
behavior

¢ denial is always an issue; it has been a national problem since the
beginning of the epidemic

e those receive antibody testing, and those who test positive once they
are tested; are more likely to reduce high risk behavior

¢ a feeling of personal susceptibility and the feeling that one has the
skills to negotiate safe sex are associated with decreases in high risk
behavior.

This is just a partial list. Therefore, my second recommendation is to fund
additional studies to describe the characteristics of those who have changed
in comparison to those who have found it difficult to change behavior so that
intervention programs can be aimed at groups who have the potential to
spread the infection to others or to be infected themselves.

Descriptive Studies Are Not Enough

Can we afford to wait for the descriptive studies to be completed before
embarking upon intervention research? The answer clearly is no. We need
behavior change studies, but the need for behavior change is urgent. We
need a broadly based and coordinated set of studies that will help us to
identify strategies for various segments of the population that are useful
and effective in preventing further infection.

We know already what the principles of behavior change are. For risk
reduction to be effective, we first need to arm people with the information
they need to make choices. We are good at disseminating information, and
many of the programs now in place are continuing to pursue this objective.

More difficult to accomplish is the need to teach skills. For people to
change, they need to know how to perform the activities that will protect
them from infection. In the case of AIDS, this means that people need to
have the technical skills to practice protected sex. It also means that they
need to have the social skills to put them into place.

Finally, intervention strategies need to shift community norms so that
when one individual decides that he or she wants sexual relations with
another individual, both will expect that one or the other could refuse. If
they decide to engage in sex, they will both expect that the other would want
them to practice safe sex.

 

 
 

ene ae RDA AAE ee OF Tae IP MET Mat ate aR ae ee ew

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS--February 20, 1988--Please do not quote or cite without permission, Thanks!

Research in Community-Based Programs

We mentioned before that behavior change in San Francisco has been
important, significant, and sustained.

The changes observed in San Francisco, compared to those made in
other cities, reflect the results that can be expected from concerted and
systematic community organization and program focused on knowledge,
skills, and shifting community norms. Six elements contributed to the
success of the San Francisco risk eduction program:

* (1) a community-based program including strong leadership from
within the gay community;

(2) market research techniques to identify appropriate messages
and communication channels for reaching the target
audience;

(3) programs to inform and motivate target audiences

(4) specific methods to teach skills and to facilitate social and
cultural change;

(5) reliance on multiple channels of communication including
print, broadcast, and face-to-face channels of communication;

(6) broad-scale grass-roots participation.

Essential to this program was the fact that it built upon the strengths
and issues of the community. Gay pride and survival, and a sense that this
community needed to save itself because no one else would, were the
underpinnings of the efforts. Non-discrimination and a pro-gay attitude
were needed to bring the population into the movement.

My third recommendation, is that the NIMH in collaboration with other
relevant agencies, undertake a controlled trial of the efficacy of community
intervention programs in reducing high risk behavior.

The behavioral sciences are faced here with the need to impact high risk
behavior with enough strength to prevent the virus from spreading. This
means changing the behavior of enough individuals over a long enough
period of time to prevent substantial spread of HIV. This requires the
power and potency of a community program approach that attends to
information, opportunities for teaching skills, and methods for shifting
community norms.

Research in Change Strategies

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS-February 20, 1988--Plcase do not quote or cite without permission. Thanks!

The National Cancer Institute has, for the past 7 years, been sponsoring
research in smoking cessation that could prove to be a useful model to
prevent the spread of AIDS. Some 45 individual investigations have been
funded to develop, implement, and evaluate various strategies for reducing
smoking in various segments of the population. Investigators come
together periodically to plan studies and programs, and to share results. I
have been involved with this process with the NCI and I believe that it has
pushed smoking cessation programs much further along than almost any
other area of health behavior change.

My fourth recommendation is that the National Institute of Mental Health,
in collaboration with other relevant agencies (e.g, the CDC, the National
Institute on Drug Abuse) support a coordinated set of studies aimed at
programs with high risk populations or avenues of intervention. High
priority populations are

¢ gay and bisexual men who still comprise 65% of the cases of AIDS
and 80% of the estimated individuals who are infected
with HIV but not yet diagnosed with AIDS

¢ special emphasis within this group should be given to minority
gay and bisexual men? and to homosexual youth.

¢ IV drug users and their sexual partners.

¢ adolescents, especially ethnic minority adolescents in areas where
rates of sexually transmitted diseases and unplanned
pregnancies are higher

® persons presenting for treatment at sexually transmitted diseases
clinics

¢ individuals identified as positive for antibodies to HIV at the
Armed Forces Recruiting Centers? These individuals may not
enjoy the support of other individuals who are in the same
situation and may need special programs to prevent spreading
the infection to others.

¢ ethnic and minority women.

¢ prostitutes and others in the sex industry.

 

2 As of this writing, the NIMH is supporting only one study in this area, and this is a
descriptive study of Black gay and bisexual men. No intervention studies are being
supported, and no studies focused on Hispanic gay and bisexual men are being supported.
3 The Armed Forces reported in July that 0.15% (1.5 in 1000) of individuals presenting for
recruitment were positive for antibodies to HIV. The ratio of Blacks to Whites was 2.5 to 1.
In five Jocalities (New York, New Jersey, District of Columbia, San Francisco) the
prevalence was 1 in 100 or 1%.

 

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS-February 20, 1988-Please do not quote or cite without permission. Thanks!

In addition, programs of research can be focussed on specific methods for
reaching various populations including,

¢ health care providers and health care delivery institutions
¢ media

¢ school-based programs

¢ clinic-based programs.

I propose that programs of research be developed in each of these areas. In
each area, a minimum of 5 to 7 studies should be funded to reflect national
distribution. The investigators should be encouraged to request funding for
at least five years, and the best methods of science should be employed to
plan the studies and to evaluate outcomes. The studies should be designed
to shed light on basic behavioral processes as well as to develop
disseminable programs. The investigators should be brought together
semi-annually to plan their studies and share their results, The best place
to accomplish this research is within the NIMH, hopefully within the AlDS
Branch to be established there.

Costs

The costs for this program of research are estimated to be around $100
million over a 7 to 10 year period of time. This is a small amount of money
in comparison to what it will cost if we continue to go on with business as
usual.

A Final Note

We all recognize that we are working in a delicate arena. We are not
dealing with smoking or exercise, or weight reduction where individuals
can agree on what kinds of changes can occur. We are working in the area
of sexuality, and we as a society have deep feelings about sexuality. It is
important to discuss sexuality with all of its moral, philosophical,
psychological, and societal implications. But we cannot afford to let this
discussion get in the way of preventing spread of infection. Part of the
research agenda must be methods of resolving these differences so that
important work can go forward.

The AIDS epidemic is not the first epidemic of sexually transmitted
diseases in the past two decades. Herpes, chlamydia, and unwanted
pregnancies are serious national problems. Efforts to take care of this
problem have been hampered by a variety of issues, not the least of which is
our reluctance to solve our philosphical differences and our squeamishness

10

 

 

 
 

 

Thomas J. Coates, PhD--Draft--2/12/88--Testimony before the Presidential Commission
on AIDS-February 20, 1888--Please do not quote or cite without permission. Thanks!

to discuss things sexual in public. I am glad that we have the opportunity

to do this. The program of research we have identified wil] be important in
dealing with the whole range of sexual issues in our society. Hopefully, we
can put in place an effective program so that we are never again caught off

guard.

11

 

 
 

STATEMENT FOR

THE PRESIDENT’S COMMISSION ON AIDS

SEX RESEARCH AND THE AIDS CRISIS

by

Bruce Voeller, Ph.D., The Mariposa Education and Research
Foundation, Topanga, California

June M. Reinisch, Ph.D., The Kinsey Institute, Indiana
University;

William M. Masters, M.D. and Virginia E. Johnsen, BD. Se.,
The Masters and Johrissan Iastaitute,
St. Louis

Tn spite of ivnereasing public acceptance of the significance of
various aspects of intimate behavior Far normal adult ouman functioning.
relatively sparse funding for research into this fundamental dimensicn
of human existence has been available during the last S@ years. AS a
cansequence, there exists only a limited bady of scientific data tipon
which ta base scaurid public health, social, religious, and legal policy
decisicns. In spite of their obvicus limitations, the existing data
sets wher used appropriately, can provide initial guidance in cur
efforts ta central the progression of the AIDS epidemic in the United
States and around the world.

The AIDS crisis poignantly demenstrates the limitations af cur
current knowledge in this area, and underlines the urgency of our need
ta expand the bedy of reliable information crucial to the establishment
of effective and efficient national policy. It 1s vital that we develop
dependable, current data regarding the sexual practices and attitudes of
various segments of our saciety linked to accurate estimates af the size
and demagraphic camposition of these diverse communities. Makeshift
studies, crudely formulated and conducted interviews, and popular
Magazine surveys provide reugh sketches of what people may be deang and
feeling, but such efferts are simply inadequate ta the task of preaviding
the type of infermatian upon which meaningful predictions, interventions
and salutions can be based. The techniques ta derive and carry cunt
research conmernsurate with our critical needs have been develcped during
the last several decades -- we are lacking only the will and the means
necessary toa underwrite such a crucial preagram.

 

 
   

  

 

Establishment of an adequate data base requires the funding and
conduct of saphisticated, bread spectrum, in-depth, multidisciplinary.,
research conducted with individual subjects. In essence, appropriate
research musts

a) be designed with the assistance of representatives froin
the diverse age, racial, ethnicity, and socicecanamic groups
within our saciety;5

b) be based on proper sampling techniques of the nation as
a whole, including sufficient sampling of minority populations;

c) be culturally sensitive; and,

d) unvalve highly trained and experienced interviewers,
themselves drawn from diverse segments of cur society and
employing advanced interviewing techniques and methadaleagy.

Modern research has made it clear that the medical, physiological
and related bislogical aspects of sex are exquisitely intercanmected
with the behavioral expression of sexuality. The present data base,
while providing tantalizing suggestions for the prediction of the spread
of the AIDS virus and the potential control of its transmission
throughout our population, is woefully imadequate in providing answers
to many of the most basic questions concerning sexual, reoraductive, and
developmental physiclagy and their cellular ard hormonal foundations.
These must be addressed if effective action is to be undertaken.

Our lack of fundamental knowledge pervades the whole range af
problems regarding the AIDS dilemma. At one end of the spectrum, we
know very little indeed about the actual sexual practices of the
American pecple; the factors that shape their expression in particular
communities; and the forces which serve to block or facilitate change in
attitudes and behavicr. In another domain, while we recognize the
urgency for increased condom use, ever such simple questions as, "What
are the pressures and frictional stresses to which condoms are subjected
during intercourse?" remain to be answered. This latter issue leaves
scientists evaluating the effectiveness of condoms as a barrier against
infection, while lacking the most elementary laboratory standards with
which to judge the protective capacity of the condom in practice. in
fact, we do not even know what constituent (s) of semen is the infectious
component(s). Is it free virus? Is it HIV-laden lymphocytes or
macrophages? Is it virus-beund sperm? The answer 15 unk nowre!

Inasmuch as the viability of the AIDS virus is strongly pH
dependent ard inactivated at low pHs, we must ask whether acidically
buffered vaginal creams, gels and spermicides could provide a hastile
environment for HIV at pHs still tolerated by the vagina and penis”
Also, we must ask whether the HIV in semen is lecalized on sperm or
within white blesd cells as noted above and, if sea, whether vasectomy

 

 
 

 

Wwauld diminish infection af sere-negative women by HIV pasitive men.
Hemoaphaliacs might provide a madel test case, inasmuch as 3Q% of them
are sere-positive and many are vasectoaomized. Numerous similar
possibilities are evident tm sex physiclagists, but these possibilities
go unneticed or ignored by those at the helm ain planning the course of
AIDS research and education.

We recommend the establishment of a multicerntered national program
for the collection of the widest possible range af behavioral and
biomedical profiles of cur nation’s population(s). In order ta
accomplish this goal in a marmer which will permit develapment of a
compelling national strategy, the research must include the full panaply
of ethnic, racial, economic, religious, saciosexual, ard age groups
which comprise sur saciety. These constituent groups must be included
both in the design and conduct of the research as well as serving as the
diverse foci of study. It is vital that this effert include face-to-
face interviews of a large sample of Americans from teenagers ta senior
citizens, from rural towns to the urban irmer cities. If come thirg is
clear frem the currently available behavioral data, it is that no real
boundaries exist ameng the diverse groups of cur culture. The econanic
and secial mobility of our population, of which we are gustly proud as a
nation, 18 e@aually relevant in the sexual sphere -- heterosexual and
hamesexuals asian, hispanic, black or white; old or youngs rich or poor;
east or west-~ all are part of the cverlapping communities which farm
our society. All must be studied and understood if cur ccaunmtry ard the
rest of the world are tx caste aff this dread disease.

 

 
 

 

TESTIMONY TO THE PRESIDENTIAL COMMISSION ON THE HUMAN
IMMUNODEFICIENCY VIRUS EPIDEMIC

John H. Gagnon, Visting Professor of Sociology, Department of
: Sociology, Princeton University

 

I have spent a gaod part of my scientific life interested 1n
the social and psychological dimensions of human sexuality ---
that is, I have attempted to do research that would increase our
understanding of the role that sexuality plays in both the lives
of individuals and in the collective life of the society.

I do not think that I have tg re-~iterate the constraints
under which such a research career has operated. One need only
examine the recent publication of the Institute of Medicine,
Confronting Aids, and examine the frequency with which the work
of Alfred Minsey and his colleagues 18S mentioned to get some
flavor of the limited amount of information that we have about
the sexual life of persons in this society. That we cite data
gathered nearly half a century ago to suggest parameters for
contemporary conduct is more than problematic. Who does not
believe that the general patterns of sexual conduct have changed
Since the end of World War II and the end of the penultimate
decade of the twentieth century? Yet who would argue conclusively
that they know, except in the most gross terms, what has happened
to sexual conduct inside of marriage, to sex among young people,
to sex between men and men, to sex between women and women, to
sex between married persons and persons who are not their
spouses, to bisexuality, to sex between those who pay for sex and
those who are paid for it?

This is not to say that no data on human sexuality have been
gathered in those decades. Some limited data on heterosexuality
among young people has been systematically gathered since the
early part of the 1970s. Data on age at first coitus, estimates
cf coital frequency, a little data on sexual partners have been
gathered primarily from young women and less often from young men
in the context of studies of pre-marital fertility and
contraception. I know of only one carefully conducted national
study of the sexual conduct of young people which touched on a
wide variety of sexual issues in this period. The work of the
Jessors on young people in the early 1970s and the recent work of
Richard Udry are signal and rare examples of sophisticated
research in psychosexual development. We do have some information
on the coital experience of married women, usually based on a few
items. Again this data has been gathered in studies which have
been primarily concerned with fertility behavior. A number of
interview studies of convenience samples of gay men and lesbians
were conducted in the late sixties and early seventies. These
studies were conducted well before the current surge of AIDS
related research on gay men which began in some cities in 1985.
There is also one national sample survey study of attitudes
toward homosexuality which also asked some sex behavior
questions, conducted in 1970. Im addition there have been a
number of smaller and more focussed studies on sexual dysfuncticn
in marriage, on sexual psychophysiology, on sexual functioning in
the seriously :11, on psychological responses tO erotica, and cn

 

 
 

 

sexual violence and victimization, which have yielded some
valuable insights. Indeed one can find other studies that
reference the sexual, if they do not confront it directly. There
are, for example, studies of cohabitation, that ina patchy way
tell us something about contemporary sexual life.

Everyone concerned with the AIDS epidemic knows about the
lack of easily available and relevant databases. However, there
are other consequences of the lack of a systematic program of
research on sexuality over the last forty years that may not be
as apparent as a simple lack of data. We do not have at the
present time an accumulated survey research tradition about how
to ask questions about sexuality that will provide us with valid
and reliable answers. A brief examination of the recent Handbook
on Survey Research edited by Peter Rossi and others, and the two
volume work on measuring sujective responses in surveys (edited
by Charles Turner and Elizabeth Martin) will suggest how much
instrument design rests on art and not on science. We still need
to learn how to ask questions about sexuality in all its guises.

 

Unfortunately we don’t have much accumulated wisdom and that
which has been developed has largely been misplaced, if not lost.
Asking questions about sex is not the same as asking questions
about fertilaty, or contraception, or even abortion, or other
"taboo topics”. There is some knowledge about sexuality in terms
of data sets and instruments, but it needs to be gathered
together. I worry that in the press of wanting to get something
done quickly we will re-invent a series of square wheels that are
square 1n different ways, so that we will not be able to discover
in what ways they are out-of-round. In my view it is easy to go
wrong in this area and that more care needs to be taken in the
design of studies from instrumentation to sampling to data
analysis than is being currently invested.

The absence of a serious scientific research tradition in the
area of sexuality does not mean that we have lacked "reports" on
sexuality produced by all manner of "experts". Magazines of all
s--ts include questionnaires in their pages which they ask their
readers to fill out. Persons with "credentials" hand out self
administered questionnaires to receptive groups or they interview
Small numbers of volunteers. These are then packaged as "reports"
on sex, love, intimacy, and desire. They are the fakelore that
flourishes in the absence of carefully designed research and they
compete with the findings from good research. Indeed I have seen
data from these "fake" surveys used in serious scientific studies
because of the demand for knowledge. How much will this fake-
knowledge about sexuality interfere with learning about sexuality
or AIDS or indeed interfere with behavior change that might be
necessary? I don’t know, but the illusion of knowledge may be
worse than the knowledge that we are ignorant.

There is a dangerous belief that that anyone can do sex
research simply by making up a questionnaire and asking
questions. It 1s this that has resulted in a number of studies
that are of high quality from the biological or medical side
having weak social and behavioral science underpinnings. Samples
are poorly selected, interview schedules inadequately designed,

 

 

 

 
 

 

and questions badly asked. Much of AIDS research is
interdisciplinary research and the lack of a sex research
tradition in the behavioral sciences means the lack of trained
personnel who are experienced in the design of sex research for
these studies. While a high level of general methodological skill
is necessary, it is not sufficient to the task. Researchers need
to have substantive knowledge about sex as it is exists 1n
different cultures and social contexts. Sex 25 not just another
commodity that a market research firm can ask a question about.
It 15 not enough to be able to ask about soap today, cars
tomorrow, sex the next day. Sex is not a topic that should be
unthinkingly plugged into the standard interview format.

Perhaps what concerns me the most about the rising concern
with sex 1S 1tsS association with disease. Most of the work that I
(and some others) have tried to conduct has been linked to trying
to understand the way sexual conduct was intertwined with the
rest of social and psychological. life. The key phrase is "to
understand”. The current interest in collecting data on sexuality
is driven nearly entirely by the presence of the AIDS epidemic,
much as our interest in adolescent sexuality is driven by a
concern with adolescent pregnancy and sexually transmitted
diseases. The sex questions that are selected to be asked (of all
the questions that could be asked) are generated by a concern for
disease transmission or some other sex-related social problem.

A weak consequence of this concern 1s that what 1s
interesting about sex is what the disease makes interesting. A
strong consequence 15 that concern may make us once again see sex
as a disease producing or sin producing form of conduct. One can
_observe consequences of this movement in a variety of contexts:
in the selection of interview items --- a question 15 asked about
fisting or anal-oral sex as 1f they were part of the standard
repetoire of sexual activity --- rather than conduct that 15
generated by context and script. In the discussion of how to
manage the epidemic, sex has become a vehicle for disease
transmission rather than a form of conduct that is complenxly
related to pleasure, sin, reproduction, getting old, growing up,
and the like. This medical model tends to simplify and distort
the role that sex plays in our lives.

It is not the the job of those who are interested
specifically in controlling the epidemic to gather data with
larger purposes of "understanding sexuality” in the sense that I
mean it. AIDS must be managed and controlled and everyone
applauds those goals. At the same time we need to think about the
potential downside of our scientific and statistical interests.
Research on sex that is driven entirely by a concern for the
disease may provide us with a very different view of sexuality
than one driven by a concern for the larger roles and purposes of
sexuality in culture and society. AS we all know, the visions
that science provides of various forms of conduct is
consequential for the culture and society. The information about
sex that AIDS researchers create and publish will be widely
consumed as evidence about sex. Yet after the AIDS epidemic is
history, sexuality will continue to provide humanity with both

pleasures and difficulties.

 
 

 

Finally a narrow view of the sexual may work 2n social
bookkeeping and epidemiological modeling, but 1t may be
inadequate as we think about the more complex task of behavior
change. Here sexual conduct is embedded in culture and in social
relations and as we think about this dimension of the epidemic Wr
may need to know more than how old and how often and with whom
--- we may need to know a good deal more about why. This detailer
cultural knowledge about sex can only be gathered by an approach
that seeks to understand the way in which sexuality is embedded
in social and psychological life.

What are the practical consequences of these observations and
what can the committee do to promote then:

1. Research quality control: A great deal of AIDS research iS now
going forward and more is coming on line which involves the
gathering of sexual data. It is important that the very highest
levels of research quality control be supported and this should
involve peer review of projects both in the biological and
behavioral sciences for the specific adequacy of their sex
research components. This is not only in reference to surveys,
but to the instrumentation of bio-behavioral studies as well.
This 1s not a high cost item, but it requires systematic
administrative attention across those agencies that are funding
and doing AIDS research with a behavioral sexual component. It is
particularly important to resist the "need to know yesterday
syndrome". If this requires increasing intramural staffing and
funds for research review, this should be done.

2. Research Coordination: With the growth of research there is
also a proliferation of differing techniques used in various
investigations. It would be valuable if an ongoing review of
research initiatives involving sesuality across federal agencies
could be instituted to increase the use of common techniques or
at least the awareness of tested and useful approaches to
Gathering sexual information. No one wishes to constrain the
imagination of independent researchers, but attention to what is
already known is critical. A mechanism to increase awareness may
be, necessary .

3S. Research in Methodology: It is absolutely critical to have
some proportion of the funds given for AIDS research in the
behavioral sciences ( as well as the behavioral aspects of bio-
behavioral studies) directed toward methodological research. In
the haste to get data, careful methodological checks are not
preformed and studies come to nothing oer worse. There is a
desperate need to do a number of methodological studies pricr to
the time that major research initiatives are taken or these
studies need to be done while the initiative is going forward.
The RFP for the new Household Seroprevalence Study takes some
steps in that direction. Perhaps some percentage of funds given
to agencies should be targeted for methodological research. I do
not mean this to inhibit research by nitpicking, but to suggest
that careful work on an accelerated schedule be undertaken.

4. Training: The lack of a research tradition means a lack of
trained Personnel. There are very few well trained sex

 

 
 

researchers in the United States. Often the very best have been
self trained. Further the AIDS epidemec calls for the ability toa
do interdisciplinary work. The epidemic will be with us for at
least another decade and its consequences perhaps longer. There
is a desperate need to establish a number of innnovative
interdisciplinary training programs at the pre-doctoral and post-
doctoral levels. These need to include training for professionals
from the less developed countries, particularly Africa.

5S. Support for general sex research: It 18 important to start to
support sex research which is more expansive 1n its interests
than that which is driven by the AIDS epidemic itself. While the
committee has not been given responsiblity for such issues 1t 15
clear that if we had a better general knowledge of sexuality and
how it was changing 1n the society we would have been better able
to respond to the AIDS epidemic.

6. Data Archiving and Data Sharing: While there is not a great
deal of accumulated data on sexuality there 1s some which would
be helpful in developing new instrumentation and offering
evidence about rates of change. Data should be archived (in the
same way we store blood) at a number of sites. Funds should be
made available as part of the funding process for new research to
carefuly archive data tapes as well as raw data if necessary.
This simple act would increase data quality control. As a
correlary to this 1t is imperative that data (including
instruments and whatever other information required for
understanding how a research project was conducted) be rapidly
shared. This includes data gathered under contracts, grants, and
cooperative agreements. Principle investigators (both extramural
and intramural) should be given time to publish their own work,
but this should limited so that other scientists can benefit from
federally funded data gethering. Perhaps as part of the process
of receiving funds from the federal government, researchers
should agree to make data widely available, restricted only by
limats of confidentiality.

 

 
 

 

Testimony on Research and Prevention Efforts about Intravenous Drug
Users and their Sex Partners

by
Samuel R. Friedman
Narcotic and Drug Research, tnc.

Given the probability that we will not have either vaccine nor therapy
for AIDS in the near future, prevention of HIV spread is crucial to pre-
vent the spread of the epidemic. Unfortunately, we do not have ade-

quate knowledge about the best ways to do this.

Thus, we need to learn how to affect risk and transmission behavior.

This behavior is social behavior: transmission involves at the least an

 

interaction between two or more persons, and the context that leads to
contaminated syringes being shared can involve small group pressures
as well as a wide range of broader social factors including race and the

particular laws in a jurisdiction.

The complexity of these factors for IV drug users is shown by abundant
evidence that in spite of their chemical dependency and, often, their
lack of education and their alienation from social institutions, many IV
drug users have taken actions to protect themselves and others (and
thus that stereotypes are wrong), and that they did so even before any
prevention efforts were aimed at them; and by the complexity of the
factors that mean that gay men’s organizations have been set up to deal
with AIDS, but that drug users have been much less prone to do so (but,

nonetheless, that the junkie unions in Holland have taken on AIDS).

The complexity of these issues poses difficult methodological and re-

 

 
 

 

search problems:

A. By and large, research has focused on what helps the individual to
reduce his or her personal risk of becoming infected. This re-
search has used the experimental model from psychology as 4
model, which means that it looks at individuals as the unit of
change and that it assumes that history is irrelevant (i.e., that
what works at one point and time during the epidemic wil} work
at other times and places.) Research has to get beyond this in
several ways:

1. Focus also on reduction of behaviors that potentially trans-
mit HIV to others. This is a different set of motivations
than personal protection. Many IV drug users are more will-
ing to listen to outreach workers when the issue is raised
as how to protect loved ones rather than self-protection.

2. Look at prevention efforts that take seriously the fact that
risk behaviors -- both IV drug use and sex -- are social. We
are beginning projects to change the values of IV drug users
and their partners to reduce transmission and to help them
develop ways to implement such protective ideas in prac-
tice Gne example is street user self-help groups to get

peer support for risk and transmission reduction.

3. Look at risk and transmission behaviors as historical
events. At the beginning of the epidemic, few drug users
believed in their own vulnerability to AIDS; since then,
more acceptance has occurred, and considerable risk and

\
transmission reduction; later on, we mayyencounter a sub-

 

 
 

 

culture of despair about AIDS. Each of these periods in-
valves different contexts for the individual who is con-
fronted with 4 given intervention, so we would expect reac-
tions to differ in accordance with the history of the epi-
demic. The standard models of research, however, do not
take this dynamic into account, nor the fact that the stage
of the epidemic may differ in different cities.

. Decisions about research into behavioral change and preven-
tion programs are often taken by medically trained persons
-- often, by superb medical scientists. They make these de-
cisions -- about what programs should be set up for funding
through an RFP mechanism, what specific proposals should
be funded, and what articles should be accepted or rejected
-~ on the basis of their medical research training. Their
input into these decisions is of course useful, but social
scientists have necessary expertise and experience that
also has to be included in decision-making. Medical training
tends to be of only limited applicability to the social sci-
ence research we need in order to figure out how to change
the behaviors that spread this epidemic -- for example, it
exalts the experimental methad, ignores issues of histori-
cal change during phases of the epidemic, and simply as-
sumes that the individual is the appropriate unit of analysis
-~ and thus produces requirements that hold back the devel-
opment of innovative research. The fact that medically-
trained researchers are often unaware of these issues sim-

ply aggravates the problem.

 

 
 

 

5. Here, the-history of national research policy just prior to
AIDS becoming & major recognized threat is a warning to us.
Good social science in AIDS is rare -- as has been pointed
out by both the National Academy of Sciences and the Amer-
ican Foundation for AIDS Research. This is due, in part, to
the restriction in social science research funds in the early
1980’s. Decisions such as that to have NIMH focus on the
biological aspects of mental health, and to move away from
funding social science research, meant that when AIDS hit
we had had less research into drug use and its prevention,
into sexual behavior, and into the methods for studying
these topics; and that we also had a shortage of researchers
with skills in these areas.

6. AIDS means we have to examine and test some ideas that
are controversial in order to protect the public health. In
Sweden and Germany, methadone treatment is itself contro-
versial, but in Sweden they have doubled methadone treat-
ment in response to AIDS (from 150 to 300 slots, which is
30% of their heroin users), and in Germany they have sy-
ringes sold over the counter and have made sure that phar-
macists actually do sell them to addicts (and in Sweden
they have an accepted unofficial syringe exchange). In the
US, controversial issues include syringe exchanges and

methadone without supportive counseling and vocational

services.
Here, it is important to understand that, although it is

sometimes argued that there are contradictions among vari-

 

 
 

 

ous projects and goals -- eg, between methadone and be-
coming drug free, or safer injection programs and entering
drug abuse treatment -- experience and research alike show
that these programs support each other. Syringe exchanges
in Europe do not reduce treatment admi ssions, and teaching
New Jersey users about how to use bleach to clean syringes
led to increased demand for treatment.

7. We absolutely have to be able to do research in these con-
troversial areas if we are to learn how to prevent the
spread of AIDS. Federal agencies, however, are inhibited on
this. The CDC Innovative Research Projects have been hin-
dered by requirements that local committees approve edu-
cational materials. Calls have been made for experimental

tests of needle exchanges, but so far none have been funded.

There is no apparent compelling logic behind why some ap-
proaches are accepted in one country and rejected in anoth-
er; or why the particular ideas that are controversial in one
country are nonetheless tested out, while in the US such re-
search is stymied.
Ilt. Specific suggestions about research management |
A. We are reaching a point where we cannot train medium level re-
searchers at the rate we need through normal channels. We need 4
way to bring established researchers who have not been doing
AIDS research into our on-going projects through @ senior-level
equivalent of a post-doctoral program; appropriate persons might

be associate professors who want to change careers or who have

 

 
 

 

sabbaticals. Stipend levels would be in the order of $35-50,000.
This would let us train needed project directors and senior ana-
lysts and methodologists without having to give them line au-
thority in research grants while they are being trained. It might
also help us reduce the serious paucity of minority researchers in
this field (which is important in research about behaviors that
lead to disproportionate infection of minorities.)

B. Expansions in research funding have not been matched by funding
agency infrastructure expansion. This means that researchers
have not had adequate support by staff of agencies such as NIDA
due to the extreme overload of responsibility on Federal staff.

C. AIDS research moves fast, and often does not fit funding cycles
well. Sometimes, grants are initially budgeted small, but it turns
out that they need and deserve considerable expansion in mid-
year. The mechanisms to do this are very awkward, and need
stream-lining.

IV. Research that has been done suggests the following interventions to
reduce AIDS among IV drug users and their partners:

A. Prevent initiation of [V drug use. Much research is needed on this.

B. Rapid and sizable expansion of drug abuse treatment. We have ca-
pacity for perhaps 10% of IV drug addicts, and considereble wait-
ing time to get into treatment. We need improved levels of space,
facilities, and staffing, since research shows that these affect
the extent to which clients alter their behaviors.

C. Outreach to IV drug users and their partners has begun, but needs
expansion and additional innovation. This should include individ-

ual educational outreach, efforts to promote safer injection, and

 

 
 

 

aiso efforts to mobilize the small groups and subculture for AIDS
prevention.

D. Given the extent to which AIDS is impacting Blacks and Hispenics,
special programming to involve minority community organize-

tions and institutions.

 

 
 

 

Supporting Materials
|. Background -- Des Jarlais presented this in fuller farm
A. IV drug users have attempted to protect themselves and others
5. Many have not been able to do this consistently
C. Thus, prevention projects that work with users to make it easier
to reduce transmission ta them and from them are appropriate
Hl. [Issues in an evaluation include:
A. Who and how many take part?

1. They do not flock to be tested

a} Magura -- 10%

b) Minneapolis -- almost all of an MMTP program got
tested

c) AOP

d) Partners don’t flock to Beth Israel couples study

2. Drug treatment programs

a) They are over-subscribed and have waiting lists”

b) Different modalities vary in popularity

c) Need avast expansion

3. Outreach models

a) AGP 3000 contacts per month

b) vans for partners

B. Does it work? This is complicated to figure out the appropriate
measure for success. For immediate impact -- over a year period
or even more -- all we can measure is changes in risk behaviors
and in related indicators such as knowledge and program atten-
dance. Over longer time periods, we can try to measure infection.
In all these evaluations, a critical issue is whether the evalua-
tion focuses only on the individual being intervened with, or upon
the totality of IV drug users/partners in a given area.

1. We know some about impact an knowledge, self-reported
behavior change, and treatment entry We know nit on im-
pact on infection.

8) Testing -- may work if excellent counseling, and vol-
untary. We suspect that the counseling 1s the key, not
the testing.

(1) Casadonte

(2) Cox (Montefiore)

(3) Marlink study of New Bedford IV drug users in
methadone detoxification treatment

é

 

 
 

 

b) Outreach evaluations
(1) San Francisco bleach
(2) McAuliffe
(3) New Jersey
c) Treatment evaluations
(1) Long history of studies of treatment effective-
ness | .
(2) Studies specifically focussing on effects of
treatment on risk behaviors in the AIDS era
(a) Ball -- “Good” MMTP treatment is effec-
tive, but varies
(b) Abdul-Quader et al.

d) Key finding is that of non-contradiction be-
tween efforts aiming at “safer injection” and
those aiming at ending drug use.

Ill. Innovative program ideas

A. AIDS means we have to examine and test some ideas that are con-
troversial in order to protect the public health. In Sweden and
Germany, methadone treatment is itself controversial, but in
Sweden they have doubled methadone treatment in response to
AIDS (from 150 to 300 slots, which is 30% of their heroin users),
and in Germany they have syringes sold over the counter and have
made sure that pharmacists actually do sell them to addicts (and
in Sweden they have an accepted guerrilla syringe exchange;
methadone without supportive counseling and vocational services
is controversial in US; needle exchange aproach is controversial.

B. We absolutely have to be able to do research in these controver-
sial areas if we are to learn how to prevent the spread of AIDS.
Federal agencies, however, are inhibited on this. The COC Innova-
tive Research Projects have been hindered by requirements that
local committees approve educational materials. Calls have been
made for experimental tests of needle exchanges, but so far none
have been funded.

C. By and large, research has focused on what helps the individual to
raduce risk of becoming infected. This research has used the ex-
perimental model from psychology as a model, which means that
it looks at individuals as the unit of change and that it assumes
that history is irrelevant (i.e., that what works at one point dur-
ing the epidemic will work at other times.) Research has to get
beyond this in several ways:

 

 
 

 

1. Focus also on reduction of behaviors that potentially trans-
mit HIV to others. This is 4 different set af motivations
than personal protection.

2. Look at risk behaviors -- both IV drug use and sex -- as se-
cial. We are beginning projects to change the subculture of
IV drug users and their partners in some of the ways that
gay men have changed their subcultures -- i.e., to incorpo-
rate risk and transmission reduction as important values
within the subculture, and to help users and their partners
develop ways to implement such protective ideas in prac-
tice. Here, street self-help groups among users to get peer
support for risk and transmission reduction is one example.

3. Look at risk and transmission behaviors as historical
events. At the beginning of the epidemic, few drug users
believed in their own vulnerability to AIDS; since then,
more acceptance has occurred, and considerable risk and
transmission reduction; later on, we may encounter a sub-
culture of despair about AIDS. Each of these periodsin-
volves different contexts for the individual who is con-
fronted with a given intervention, so we would expect reac-
tions to differ in accordance with the history of the epi-
demic. The standard models of research, however, do not
take this dynamic into account.

4. Decisions about research are often taken by medically
trained persons -- often, by superb medical scientists.
They make these decisions -- about what programs should
be set up for funding through an RFP mechanism, what spe-
cific proposals should be ranked well or poor (and thus
funded or not), and whet articles should be accepted or re-
jected -- on the basis of their medical research training.
This training tends to be of only limited applicability to the
social science research we need in order to figure out how
to change the behaviors that spread this epidemic -- for ex-
ample, it exalts the experimental method, ignores issues of
historical change during phases of the epidemic, and simply
assumes that the individual is the appropriate unit of anal-
ysis -- and thus produces requirements that hald back the
development of innovative research The fact that medical-
ly-treined researchers are aften unaware of these issues

 

 
 

 

simply aggravates the problem.

5. The methodological issues | have alluded to are difficult
ones. We need to find ways to lure creative methodologists
to apply their skills to help work out better ways to ap-
proach research in these areas.

IV. Specific suggestions about research management

A. We are reaching a point where we cannot train medium level re-
searchers at the rate we need through norms! channels. What is
needed is a way to bring established researchers who have not
been doing AIDS research into our on-going projects through 4 se-
nior-level equivalent of a post-doctoral program; appropriate
persons might be associate professors ho want to change careers
or who have sabbaticals. Stipend levels would be in the order of
$35-50,000. This would let us train needed project directors and
senior analysts and methodologists without having to give them
line authority in research grants while they are being trained. It
might also help us reduce the serious paucity of minority re-
searchers in this field (which is important in research about be-
haviors that lead to disproportionate infection of minorities.)

B. Expansions in research funding have not been matched by funding
agency infrastructure expansion. This means that researchers
have not had adequate support by staff of agencies such as NIDA
due to the extreme over-business of the Federal staff. At NIDA,
far example, AIDS money has multiplied by 10 between FY 1966
and 1986, and more than doubled between FY87 and 88. Staff has
increased only by a factor of 5, and in FY88 will increase only by
3 persons. Travel moneys have been insufficient to allow optimal
management end assistance to the large demonstration grants and
contracts, in spite of valiant efforts by staff. The staff shortage
has meant that NIDA has been less able to attract people into
submitting proposals for AIDS research. For those who do enter
the field, NIDA would ideally be able to provide them with consid-
erable mentoring and other guidance specific to AIDS research,
but the large volume of research as compared to staff renders
this all but impossible. The Community Demonstration Projects
are NIDA’s major expenditures on AIDS, and will involve 26 grants
and 15 contracts by the end of FY88; the unit that oversees this
has only & staff members, and many of them have only been work-

 

 
 

 

ing on AIDS for a year or two.

AIDS research moves fast, and often does not fit funding cycles
well. Sometimes, grants are initially budgeted small, but it turns
out that they need and deserve considerable expansion in mid-
year. The mechanisms to do this are very awkward, and need
stream-lining.

¥. Suggestions for Interventions to reduce AIDS among IV drug users and
their partners
A. Prevent initiation of IV drug use. Much research is needed on this.

B.

C.

Rapid and sizable expansion of drug abuse treatment, including
improved levels of space, facilities, and staffing.

Outreach to IV drug users and their partners. This should include
individual educational outreach, efforts to promote safer injec-
tion, and also efforts to mobilize the small groups and subculture
for AIDS prevention.

. Given the extent to which AIDS is impacting Blacks and Hispanics,

special programming to involve minority community organiza-
tions and institutions.

 

 
 

 

Prepared for the President’s Commission on the HIV Epidemic
February 20, 1988

AIDS IN ADOLESCENCE: BEYOND EDUCATION

Karen Hein, MD

Associate Professor of Pediatrics
Director, Adolescent AIDS Program
Department of Pediatrics

Albert Einstein College of Medicine
Montefiore Medical Center NW674

111 East 210 Street

Bronx, NY 10467

(212) 920-6612

 

 
 

 

INTRODUCTION

AS we approach the end of the first decade of the AIDS
epidemic, it is apparent that there are special considerations
for the adolescent population. Both the epidemic of AIDS and
"AFR@AIDS" have touched the lives of most adolescents.

Currently, there is a low cumulative prevalence of AIDS
cases in the adolescent population under the age of 21 years
compared to adults. While adolescent sexual behavior is a common
and controversial concern, we dre only beginning to recognize the
AIDS risk associated with this behavior.

The premise of this report is that certain subgroups of
adolescents form bridges from those adults currently infected to
a larger group of adolescents. As the virus spreads from
individuals initially infected to their partners and beyond, some
teenagers are directly in the path of the epidemic. In this
epidemic, geography can be destiny.

DIFFERENCES BETWEEN CHILDREN, ADOLESCENTS AND ADULTS

Although the Human Immunodeficiency Virus (HIV) does not
select people by age, nonetheless, there are differences between
children, adolescents and adults that have bearing on the AIDS
epidemic. Some of these differences are biologic, others are
behavioral or sociologic. Briefly stated, the differences
between affected children and adolescents are the route of
infection in young children is usually vertical from an infected
mother, the shorter mean survival time in young children, and the

need for day care and foster care for pre-school aged children.

 

 
 

 

3

Some of the differences between adolescents and adults are a
higher percent of teenage cases acquired by heterosexual
transmission, a higher percent of teenaged asymptomatic
individuals (who will become symptomatic during adulthood), a
higher percent of black and Hispanic cases, a special set of
ethical and legal issues regarding testing and informing partners
and parents for those adolescents below the age of majority,
cognitive differences in processing information, the special
medical, economic and social implications of teenaged mothers
delivering HIV infected babies, emotional differences in coping
styles, the lack of a unified community for support (as opposed
to the homosexual adult population), differences in sexual
behavior patterns (a higher percent of "sexual adventurers", less
use and availability of contraceptives), and the lack of
availability of services that are convenient, appropriate and

attractive to youth.

ADOLESCENT DATA

_ Currently, the number of reported AIDS cases in adolescents
is low (1% of all cases), but is doubling each year. Statistics
for adolescents over the age of 13 years have only recently been
reported separately from the adults. These data show that
critical differences in sex ratio, ethnicity, and reported risk
groups exist not only between adolescents and adults, but also
among adolescents from different localities. Currently, 503

young people age 13-21 were reported to the CDC as of January

 

 
 

 

4

1988 (Personal Communication, H. Gayle, CDC, January 1988). The
Centers for Disease Control reviewed AIDS cases aged 11-24 in a
1986 report.2 Thirty-seven cases were 11-17 years of age versus
1122 between 18 and 24 years. Eighty percent of the younger
males were transfusion recipients as compared to 4% of the older
group. Homosexual or bisexual males comprised 18% of the younger
group but 79% of the older group. Females in both sge groups
were mostly infected through sexual contact.

Analysis of cases of AIDS in adolescents in New York City is
instructive for several reasons. New York accounts for roughly
1/3 of all AIDS cases in the US and also accounts for 20% of the

reported cases in adolescents. 2

New York Adolescent AIDS Cases

 

Male Bi/
44% Homosexual

   

fa IV Orug

44% Abuser

Ga Female
Partner

14%
IN Blood

Product

C Other

 

 

23k

 

Figure 1

 

 
 

 

5
Analysis of 114 NYC adolescent cases 13-21 yrs revealed
significant differences (p<0.0001) in the sex ratio (male: female)
of 2.9:1 compared with NYC adults (7:1) and US adults (15:1).
Teenage cases increase with age (p<0.0001). In the US, 60% of
cases were white, whereas minority groups predominated among both

adolescent (58%) and adult (55%) cases in NYC.

New York AIDS Cases

Children |
Adults

@ Adolescents
Lee ee

604

  
    

204
60<
60
Per Cento;
304

 

 

Risk Group

Figure 2

As in NYC adults, homo/bisexuality and intravenous drug
abuse were the leading risk behavior categories in adolescents
but the proportion of adolescent cases differed from adults
(Figure 2). In adolescents, the percent of total cases was lower
for homosexual/bisexual (44%) category and higher for intravenous
drug abuser category (23%). However, female partners of high
risk males were far more common among adolescents (11%) than
adults (4%), representing 45% of all teenage female AIDS cases
(p< 0.01). Nationwide, hemophilia is the leading risk factor for
AIDS among young adolescent males (79%), but in NYC only 18% of

male cases were transfusion related.

 

 
 

 

6

In summary, with scanty information about the prevalence of
HIV infection among adolescents, analysis of AIDS cases in New
York City points to groups of young people in inner city settings
that are bridging groups to other adolescents. Previous data
about rates of sexually transmitted disease and sexual and drug
related behavior among some groups of adolescents provide a
rationale for concern.? The rapid rise in the percent of cases
in young adults 20-29 years (21%) probably includes many
individuals infected during adolescence.

The long (but variable) latency period from viral infection
to diagnosis of AIDS or death from AIDS is currently estimated to
be 7 years on average. Therefore, persons infected during
adolescence may well remain asymptomatic until young adulthood.
Evidence for this phenomenon is the observation in 1987 that 10%
of the mothers of AIDS babies in New York City were 21 years of
age or less. Although many of these young women were well, they
were identified by having an affected child. The risk of
Geveloping disease does not decrease over time and infected
individuals transmit virus while remaining asymptomatic.

The concentration of adult cases in certain areas within the
mid Atlantic states, West Coast and Florida has particular

relevance for further spread to the adolescent population.

 

 
 

 

7

CONCEPTUAL FRAMEWORK

We must create meaningful categories of risk with in the

teenage population in order to target specific recommendations

for specific groups.

The teenage population does not have a wall

around it nor is the infected adult population quarantined.

Figure 3 provides a conceptual framework in which we might

view adolescents.

 
        

PARTNERS
OF
IV DRUG
USERS

   
  
 

 
   
  

Y

PARTNERS
OF
HOMO / BISEXUALS

 

 
 

 

8

The inner circle: At the center is a group of adolescents
who are currently not at risk for HIV infection by virtue of
their current lifestyle or the absence of the virus within their
sphere of activities. These are the very young, virginal, non-
intravenous substance abusers who have not received transfusions.
Although shown as the smallest circle in the diagram, they
represent the largest group of adolescents at the moment.
However, as the individuals in this group get older or move to a
different location or engage in new and different behaviors, they
may move into a different circle putting them into a higher risk
category. Issues for them include:

. "worried well" (how to live in an atmosphere of concern
and maintain an appropriate level of concern without
undue anxiety)

. need for casual contact information (encouragement to
engage in those activities that do not put them at
risk) |

. support for sexual decision making

In the second circle are sexually active teens who are not

yet exposed. The boundary between them and the at risk teenager
is fluid and easily crossed. As the virus becomes more
prevalent, this group will shrink as the next outer circle
enlarges correspondingly.

Issues for this group include:

. knowing. (or not be able to "know") their partners

. reconsidering patterns of sexual behavior

 

 
 

 

9
use of contraceptives in general and condoms in
particular

In the third circle are the at risk teenagers. This group
is at risk of HIV acquisition because of exposure to infected
individuals. The overlapping circles forming the outside of the
model provide possible sources of exposure. Exposure can emanate
from any or several of the four groups of adults or other
teenagers shown including adult IV drug abusers, adult sexual
partners of IV drug abusers, adult homosexuals or bisexuals,
adult sex partners of homosexuals or bisexuals, teenage IV drug
abusers, teenage sex partners of IV drug abusers, teenage
homosexuals or bisexuals, and teenage sex partners of homosexuals
or bisexuals.

It would appear from the reported cases of AIDS that many of
these teenagers are most likely residing within inner city areas
in the mid-Atlantic states (New York and New Jersey in
particular) and on the West Coast. Currently minority group
youths are disproportionate]ly represented. Issues for these
groups include:

‘. decisions about testing

‘ knowlédge of serostatus of partner(s)

. need for barrier methods of contraception

. reconsideration of patterns of sexual behavior

: decisions about continuing pregnancy

. need for services geared to the adolescent age group

for crisis intervention & follow-up of HIV infected

 

 
 

 

10
teenager & partners

These categories are not mutually exclusive. The more the
overlap, the higher the risk.

This model has both heuristic and practical value in that it
can form the basis for a research and action agenda. It is
important to remember that although the inner circle currently
probably contains the most adolescents, the dimensions of each
circle are unknown and are chafging continually. . Regardless of

the dimensions, the categories each represent real adolescents.

EXAMPLES OF RECENT RESPONSES TO THE CHALLENGE

Within the past year there is growing recognition of the
special considerations for adolescents regarding the AIDS
epidemic. Initially it was hoped that the activities could be
concentrated in the area of prevention. However, it is now
apparent that, although adolescents still only account for a
small percent of total AIDS cases, some adolescents are already
infected.4 Therefore, a series of parallel activities must be
launched to address the needs of a spectrum of adolescents from
the uninformed to the "worried well" to the already infected or
ill.

The following examples are listed to illustrate the range of
responses in different parts of the country. Three operating
assumptions underlie the development of interventions. 1) the
heterogeneity among American adolescents; 2) timeliness of the

AIDS problem and 3) limitations of past interventions for

 

 
 

 

11
changing behavior in relation to sexually transmitted diseases
and drug use. We will need to go beyond traditional institutions
for teenagers (schools and health care facilities) in order to
reach many adolescents. Although most teenagers are in school,
current controversy about the role of school based health clinics
and limitations imposed by school and parental groups present
obstacles that delay necessary rapid interventions that might
curtail the spread of HIV infection. Therefore, in addition to
working within the framework of schools and the health care
system, we must go beyond to identify organizations, settings,

programs and even individuals who can directly affect teenagers.

1. NETWORKS OF YOUTH SERVING AGENCIES CONCERNED ABOUT AIDS

A few examples of networks of youth serving agencies now
exist. They facilitate the development and dissemination of
educational materials, guidelines and information. Two "Task
Forces on AIDS in Adolescents" have been organized. One on the
west coast is based in San Francisco and sponsored by the Mayor’s
office (Richard Brown, MD, Coordinator). The other, on the east
coast, is located in New York City and is currently administered
through the New York AIDS Service and Delivery Consortium (Kathe
Karlson, Coordinator). Each has participants from organizations
in the educational, community-based direct service and health
sectors. These groups have been used to facilitate referrals,
share resources, develop policies, and identify problem areas

(such as access, payment, confidentiality) for mutual discussion

 

 
 

 

12
and resolution. These initiatives have developed on a volunteer
basis but their existence might enable innovative approaches to
be developed with ongoing support in the future.

Many organizations previously involved with adolescent.
health, education or welfare have shifted to include new services
related to AIDS. The first Adolescent AIDS Program in the nation
exclusively dedicated to the issues raised by the epidemic for
teenagers has been launched in.1987 in New York City at The
Montefiore Medical Center affiliated with Albert Einstein College

of Medicine.

2. ADOLESCENT RESOURCE GROUPS

Resource groups have been formed representing various
subgroups of adolescents. Focus groups have served as advisors
to screen films, educational materials, program outlines,
advertising appeals, survey questionnaires and research protocols
requiring adolescent cooperation. Specially trained peer
counselors have helped in some supervised activities. A few
examples are: 1) The New York City Department of Health has been
using focus groups to test the appropriateness and appeal of
their brochures and educational campaigns; 2) High school
students in Bethseda formed an. AIDS Hotline in 1986 using
volunteer students specifically trained to answer questions and
make referrals; 3) the American College Health Association formed

an AIDS Task Force to help develop and oversee educational and

 

 
 

 

13
service activities on campus (including the use of peer

counselors) for the college-age population.

3- DEVELOPMENT OF EDUCATIONAL MATERIALS

During the past year, visual, audio and printed educational
materials being developed specifically for adolescents.
Availability and cost are still obstacles. Attempts to evaluate
their usefulness in changing behavior are only now being
proposed. The film "Sex, Drugs, and AIDS", for example, was
commissioned by the New York City Board of Education in 1985,
completed April 1986, modified in 1987 and is only being shown to
graduating Seniors in New York City schools. Both the original
and the modified version of this film, however, are being used by
community based programs and other school programs in other parts
of the country. Training programs for teachers, counselors and
other youth workers in the appropriate use of these educational
adjuncts are-now underway. Regional workshops have been
organized by colleges particularly in the Mid-Atlantic states and
California. AIDS related curriculum planning is being encouraged
through CDC initiatives and: The National School Board Association
(NSBA) and other health and education sponsored workshops. There
are plans to expand these activities in 1988.

There is currently no central clearing house for existing
materials. Agencies with information to offer include not only
educational institutions, but also umbrella organizations such

as the American School Health Association (ASHA), National School

 

 
 

 

14
Board Association (NSBA), The Center for Population Options
(CPO), Centers for Disease Control (CDC), and Sex Information and
Education Council of the United States (S.I.E.C.U.S.). Other
youth serving organizations such as the Gay Men’s Health Crisis,
the Institute for the Protection of Gay and Lesbian Youth
(IPGLY), and many neighborhood associations are developing

resources independently.

4. ANALYSIS OF AVAILABLE DATA

Available data are being analyzed with a focus on
adolescents. Until 1987, data were generally collected, reported
and analyzed in terms of children under 13 years of age and
adults. The Centers for Disease Control and local health
departments in areas of high viral prevalence like New York, are
now disaggregating data and adapting existing protocols and
software to enable those concerned about adolescents to separate
teenagers from age groups bracketing adolescence. The age
groupings used by various agencies differ. For example, the New
York City Department of Health has been reporting adolescent AIDS
cases ages 13-19 years since October 1987 in the monthly
surveillance reports. The reports of The World Health
Organization divide the age groups by 5 yearly intervals (e.g.
10-14, 15-19 etc). The earlier reports of the Centers for
Disease Control used the division younger adolescents (11-17

years of age) versus older adolescents and young adults (18-24).

 

 
 

 

15

These divisions each may serve a particular purpose but do make

comparisons difficult.

5. SURVEYS OF ATTITUDES, KNOWLEDGE AND BELIEFS AMONG

ADOLESCENTS

Little is known about adolescents’ views and beliefs about
AIDS. In theory, this should be a first step before developing
programs or materials in any local area. Adapting pilot
questionnaires already in use has been extremely useful to
professionals who work with youth in the area of AIDS prevention.
The more localized the survey, the more useful the results. But
local areas often do not have the time, resources or expertise to
do survey analysis. A national survey is currently being
designed for high school students by the Centers for Disease
Control for distribution in 1988.

Four pilot questionnaires have been developed specifically
for: adolescents in Boston,” New York City,® San Francisco’ and
Los Angeles.® The questionnaires could be adapted for
longitudinal use so that repeated periodic contact with different
adolescent populations could be maintained. In this way, the
spread of information, changes in attitudes, beliefs, knowledge
and behavior could be followed prospectively over the next few
years. Longitudinal surveys of drug use among adolescents have
been successfully maintained over the past decade. A similar

effort could now be launched for AIDS.

 

 
 

 

16

6. MORE WIDESPREAD CONDOM DISTRIBUTION

Condoms are being made more available by reducing cost and,
increasing distribution. Advertising has been one route to
promote use as part of safer sex practices. Targeting mechanisms ,
of distribution and barriers to teenager use is another strategy,
albeit a controversial one. A mass condom distribution campaign
was instituted in a family planning clinic serving: young adults
in Atlanta and an adolescent pregnancy program in New York City.
A survey of the Atlanta recipients who could have up to 50 free
condoms was conducted to discern the number of condoms accepted
and their fate. The appearance of "safer sex kits" containing
condoms and information relevant to AIDS on some college campuses
and the increase in condom availability via installation of .
conveniently located vending machines or other modes of
distribution are examples of recent attempts to slow the spread

of HIV in the adolescent population.

7. STUDY OF THE INCIDENCE, PREVALENCE AND NATURAL HISTORY OF

HIV INFECTION

Three types of studies could be supported, all of which are
necessary for health professionals to understand the nature and
spread of AIDS in the adolescent population: 1) incidence of HIV
infection among adolescents; 2) prevalence of HIV infection in
various subgroups; 3) natural history of HIV infection.
Specifically these studies would help elucidate modes of

transmission, geographic patterns of spread and progression of

 

 
 

17
disease from asymptomatic to symptomatic state in HIV infected
teenagers. Basic information about age, race\ethnic
distribution, means of acquisition, could be combined with a
prospective study of the extent of spread to partners. The
patho-physiologic features of HIV infections including
immunologic changes, types of opportunistic infections and
cancers, the role played by other co-factors (such as
tuberculosis, the presence of other venereal diseases such as
hepatitis B, gonorrhea, syphilis, etc.,) have not been studied in

adolescents as yet.

8. NEW FUNDING INITIATIVES

Although a variety of federal, state, local, public and
private agencies are now beginning to fund projects related to
HIV infection, the mandates and categorical definition of the
mission of each agency makes analysis of available resources for
adolescents difficult. Some of the federal agencies that have
included adolescents with other age groups in recent funding
initiatives include (but are not limited to) the following:
NICHD (National Institute of Child Health & Human Development),
NIAID (National Institute of Allergy & Infectious Diseases), NIHM
(National Institute of Mental Health), NIDA (National Institute
on Drug Abuse), MCH (Division of Maternal and Child Health), cpc
(Centers for Disease Control). One group of funding agencies,
The New York Regional Association of Grantmakers, in their

September 1987 meeting on "AIDS: An Update for Grantmakers"

 
 

 

18
highlighted adolescents in the selected AIDS issues update. 9
Thus far, few agencies have targeted funds specifically for

adolescents.

9. ETHICAL AND LEGAL CONSIDERATIONS

Ethical and legal considerations related to testing,
screening, informing partners and counselling are complex when
dealing with adults. The principles and guidelines need
modification when applied to minors. The impact of policy
decisions about testing and exclusion of HIV positive adolescent
military recruits and applicants to the Job Corps and Peace Corps
and dependent minors of adult employees in certain federal
agencies has not been systematically studied. Yet anecdotal
reports indicate severe disruption in the lives of HIV positive
adolescents and their families due to inadequate mechanisms for
appropriate counselling and following up of high risk or HIV
positive adolescents.

The HIV screening currently being conducted needs further
debate and clarification of purpose. The implications for young
people differ from adults. In particular, exclusion based upon
positive test results is an issue of immediate concern. The
young person must not only deal with the disappointment of
rejection, but is not offered ongoing help in a time of personal
crisis. In addition, the stipulation for parental notification
of test results for persons under 18 years is contrary to

guidelines for other sexually transmitted diseases.

 
 

 

19
CONCLUSION
Some of the events that have helped introduce and support
the need to recognize the distinctive features of adolescents
within the past few years include:
1986
The report of the Institute of Medicine, "Confronting AIDS"
1987

The Surgeon General’s Workshop on AIDS in Children and Their
Families

The conference on AIDS in Adolescence sponsored by The
Center for Population Options

Hearings on AIDS in Children and Adolescents conducted by
the House Select Committee on Children, Youth and
Families

Report of the New York Regional Association of Grantmakers
on AIDS: An Update for Grantmakers

1988

Testimony before Presidential AIDS Commission on AIDS in
adolescence

Invitational Conference on AIDS in Adolescents: Exploring
the Challenge co-sponsored by the Bureau of Maternal and
Child Health, CDC, National Institutes of Health
(NICHD, NIMH, NIDA), and the Society for Adolescent

- Medicine.

The basic message in this report is the need to recognize
the special needs and opportunities related to AIDS in
adolescence. Thoughtful but quick action is the goal. If we
cannot determine and deter the AIDS risk for our adolescents now,
we are likely to face massive morbidity and mortality among our

young adults in the near future.

 

 
 

 

20

REFERENCES

Manoff MD, Rogers M, D’Angelo, et al: The epidemiology of
AIDS in adolescence and young adults. Center for Disease
Control. Poster session, Society for Adolescent Medicine
Annual Research Meeting, Seattle Wash. 1987.

Hein K, Vermund S, Drucker E, Reuben N: Adolescent AIDS
cases: Epidemiologic differences related to geography and
age. Society for Adolescent Medicine Annual Research Meeting
March 1988.

Hein K: AIDS in adolescence. New York State J of Med
1987 ;87:290-5.

A generation in jeopardy: Children and AIDS. A Report of
the Select Committee on Children, Youth and Families
US House of Representatives, December 1987.

Strunin L, Hingson R: AIDS and adolescents: Knowledge,
beliefs, attitudes and behavior. Pediatrics 1987;79:825-8.

Reuben N, Hein K, Drucker E, et al: Relationship of high
~risk behaviors to aids knowledge in adolescent high school
students. Society for Adolescent Medicine Annual Research
Meeting. New York March 1988.

DiClemente RJ, Zorn J, Temoshok L: Adolescent and AIDS:
A survey of knowledge, attitudes and beliefs about AIDS in
San Francisco. Amer J of Public Health 1986;76:1443-5.

Robertson M, Koegel P,.Grell Cc: Street kids and AIDS:
Knowledge, attitudes and high risk behavior for exposure.
Special session. Presented at American Public Health
Association Annual Meeting, New Orleans October 1987.

Bryan B: AIDS: An update for grantmakers. New York

Regional Association of Grantmakers. Report of Funders
Concerned about AIDS. September 1987.

eU,5, GOVERNMENT PRINTING OFF ICE :1988-617-070:03511