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AIDS Treatment News #229, August 18, 1995
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

"Confirmatory" Trials: Symptom Reduction As Efficacy Measure

FDA Warning on Raw Oysters

ICAAC Conference, September 17-20, in San Francisco

Merck Protease Inhibitor Note: Expanded Access Program 
Registrants Should Receive, and Return, Mailed Confirmation

Alternative Medicine and HIV/AIDS: Request for Applications

San Francisco: AIDS TREATMENT NEWS Needs Office Space

House Moves to Block Internet Censorship

Is NIH AIDS Research in Danger?


***** "Confirmatory" Trials: Symptom Reduction As Efficacy 
Measure

by John S. James

The Problem

Currently, definitive efficacy trials (such as the 
"confirmatory" trials to prove clinical benefit of drugs 
which have been given accelerated approval) are laboring 
under ground rules which make these studies extremely 
difficult to accomplish in today's treatment environment. The 
critical problem is the definition of clinical proof or 
confirmation as requiring an endpoint of death or progression 
to an AIDS-defining infection. This definition -- explicitly 
referenced in the FDA's announcement of its workshop on 
design issues in confirmatory AIDS trials [see note below] -- 
assures that these trials will take years, require hundreds 
of patients, be tedious and inordinately expensive to set up, 
and be unfeasible and probably unethical to run.

Requiring AIDS-defining illness or death in order to measure 
drug efficacy locks trials into the time frame required for 
volunteers to become seriously ill or to die -- a time 
getting longer and longer as both conventional and 
experimental treatments improve. Not only are vital results 
delayed, but compliance becomes difficult or impossible as 
the standard of care changes, requiring mid-stream amendments 
to protocols -- changes which damage the interpretation of 
results. Because of the long time required for volunteers to 
"achieve" an endpoint, trials must be very large -- making 
efficacy trials impossible for more than a handful of the 
many important drugs and combinations becoming available.

These problems are well known. The question is where to go 
from here. We propose a trial design which uses symptom 
reduction, instead of death or AIDS-defining infection, as a 
primary indicator for determining drug efficacy.

Symptom-Reduction Trials

By symptom-reduction trial, we mean a clinical trial which 
recruits volunteers who have one or more designated indicator 
symptoms, in order to see if those symptoms improve as a 
result of the treatment being tested. These symptoms must be 
HIV-related, easily measurable, not intolerable, and unlikely 
to improve spontaneously or with standard treatment. Examples 
might include certain skin conditions, recurrent fungal or 
thrush infections requiring reliance on antifungals, fever of 
unknown origin, weight loss which cannot be diagnosed, or 
sleep disturbances.

Participants would be randomized into two groups -- antiviral 
treatment (for example, Merck protease plus 3TC plus AZT), 
vs. placebo or comparison treatment, for a few weeks. Both 
groups would continue their existing treatments (for example, 
antifungals) as needed throughout the trial. The primary 
outcome measurement would be reduction in the designated 
symptom(s) -- rated, for example, by blinded evaluation by 
physicians, or by reduced usage of specific medication such 
as antifungals. All outcome measurements would be defined 
prospectively.

Within weeks, with probably no more than a few dozen 
volunteers, these trials could produce statistical proof of 
clinical benefit from the antiviral treatment (compared to a 
placebo, or to a different antiviral regimen). This benefit, 
beyond its intrinsic value, would also serve as a marker for 
a more profound systemic benefit of the treatment -- namely, 
immune recovery resulting from suppression of HIV.

At the end of the controlled-trial period, all volunteers 
would be offered the most desirable treatment, and followed 
indefinitely, to see how long the effect lasted. Note that in 
this followup period, there will be two groups matched and 
randomized to be equivalent in every way, except that one 
started the antiviral treatment (say) eight weeks before the 
other. This eight-week difference will help researchers 
distinguish drug effects (both safety and efficacy related) 
from effects of disease progression, even after the 
controlled-trial period ends. Is there an eight-week 
difference in onset of the effect in question, or not?

Also note that the controlled-trial results could be 
published as soon as the controlled period ended, without 
much affecting the followup, as everybody would already have 
access to the most desirable treatment, so they would be 
unlikely to drop out or change treatments as a result of 
publication. This means that results important for clinical 
practice and for the development of new trials would no 
longer need to be kept secret for months or more by the DSMB 
(data safety monitoring board, which secretly unblinds the 
results of an ongoing trial to see if treatment differences 
are so great that it would be unnecessary and unethical to 
continue the study), or by a few researchers, but could 
immediately be disseminated and widely used.

One or two such trials (plus other straightforward research 
such as an adequate safety database, pharmacology studies of 
combination use of the new therapy with widely used drugs, 
etc.) should be enough to fully meet the requirement of 
clinical confirmation after accelerated approval.

In fact, one or two of these trials should meet the efficacy 
requirement for approval of the drug in the first place -- 
bypassing accelerated approval by making it unnecessary. 
Symptom-reduction trials can be as rapid as the surrogate-
marker trials now used for accelerated approval. And they use 
the symptom improvement -- not just a blood-test value, but a 
real clinical benefit to the patient -- as an efficacy marker 
for a deeper benefit of the antiviral.

Will it be possible to recruit enough volunteers with an 
appropriate indicator symptom for these trials? Yes, for 
several reasons. Not many volunteers are needed for each 
trial. Many people have ongoing HIV-related symptoms which 
have not responded to any available therapy. Not all patients 
in a trial necessarily need to have the same symptom. And 
many kinds of symptoms do respond to powerful antivirals; 
there are frequent case reports of many different symptoms -- 
often all of them -- being quickly and completely reversed by 
a powerful antiviral therapy (such as a protease inhibitor, 
or AZT plus 3TC plus ddC in a treatment-naive patient).

Symptom Reduction and Survival

What does symptom reduction add to the markers of HIV disease 
progression which are already in use? The best marker 
available now is generally agreed to be viral load; a 
reduction in viral load shows that the treatment being tested 
is active as an antiviral in humans. Symptom reduction -- 
using a marker symptom which is not directly affected by the 
antiviral -- shows that this antiviral activity has resulted 
in immune improvement, which in turn has resulted in a 
clinical benefit. And if the marker symptom is correctly 
chosen to have no direct response to the treatment being 
tested (for example, reduction of fungal infections could be 
used as the marker symptom only if the antiviral regimen is 
not also antifungal), then it is likely that the clinical 
benefit seen is the tip of the iceberg, that the immune 
improvement which produced the benefit which is measured will 
also be beneficial in other ways which are not immediately 
apparent.

Will this immune benefit lead to longer survival? Very likely 
yes, if the improvement can be sustained, but it will take 
years to know for sure -- just as it will take years to 
determine survival benefit in any HIV treatment trial which 
is started today (except for patients at very late stage 
disease, when it is usually hard to see the benefit of a new 
treatment). Meanwhile, we should go ahead with the best 
trials we can run now. There is no excuse to delay for years 
until survival benefit is proved.

Until now, only death or AIDS-defining opportunistic 
infection reduction has been generally accepted as an 
endpoint for a definitive efficacy trial. AIDS-defining 
opportunistic infection reduction is in fact a form of 
symptom reduction -- but with a very impractical choice of 
symptom to use as the marker, because it takes so long to 
measure the difference between the trial groups, making it 
almost impossible to design trials which are workable, 
reliable, and ethical. Trial designers need permission to 
select more workable symptom-reduction markers if they 
choose.

Looking for improvement in existing chronic symptoms ties a 
trial to the time frame of drug effects -- days or weeks. But 
waiting for new symptoms to develop ties the trial to the 
time frame of HIV disease progression -- months or years. 
Confining clinical confirmation solely to changes in death or 
progression to AIDS might have made sense in the time of 
BW002 (the early AIDS trial which led to the approval of 
AZT), but it does not make sense today.

Today, the choice of AIDS-defining opportunistic infection as 
the definitive endpoint for efficacy trials has no scientific 
basis, benefit, or rationale. It rests on the historical 
inertia of an AIDS definition created years ago for other 
purposes. It is used because it is believed likely to be a 
good surrogate for survival, although this has not been 
proven.

But survival itself -- despite its transcendent value -- 
becomes less and less feasible as the gold standard for 
measuring trial results, as treatments improve and survival 
lengthens. Demanding survival (or a known surrogate) as the 
endpoint in efficacy trials effectively prevents these trials 
from being designed and run successfully. The fact that 
survival is the ultimate goal does not automatically make it 
a useful guideline for the practical work of designing 
feasible and productive trials.

Suppose that a treatment causes a patient's viral load to 
decrease by a hundred times or more, and CD4 count to go up 
by two to three hundred or more, and all HIV-related symptoms 
to disappear -- and that this effect can be sustained, 
through use of various treatments -- can we prove that the 
patient will live longer as a result? No, we cannot prove it, 
short of a clinical trial which will take years. So we have a 
choice to make. We can insist on certainty and demand the 
survival data -- at the cost of making confirmatory or other 
efficacy trials prohibitively difficult to run, and 
guaranteeing that AIDS drug testing will not meet the needs 
of the epidemic. Or we can take a small chance of being wrong 
(the chance that the patient, even with all these 
improvements, is not really better off in the long run). By 
accepting this small chance of error, we open many 
opportunities for rapid, feasible, and useful testing of 
attractive new drugs and combinations. The choice is ours.

History and References

AIDS trials do of course report the development of symptoms 
less serious than AIDS-defining opportunistic infections. But 
we do not know of any trial which has used an existing HIV-
related symptom as an indicator of effectiveness of an 
antiviral or other treatment for HIV disease -- requiring 
that patients have the symptom when they enter the trial, and 
using improvement or disappearance of the symptom as the 
primary measure of drug efficacy.

A recent article, "Selection of Endpoints for Assessment of 
Treatment Efficacy in an AIDS Trial" (by David A. Amato, in 
AIDS Clinical Trials, edited by Dianne M. Finkelstein and 
David A. Schoenfeld, Wiley-Liss, 1995), explores the critical 
difficulties in the selection of workable endpoints today. 
This article includes two sentences on time to development of 
non-AIDS-defining symptoms as a possible endpoint -- but no 
hint of reduction of existing symptoms as a measure of drug 
efficacy.

Outside of AIDS, however, the idea has been discussed, with 
different terminology. Researchers have noted that a therapy 
"'tested in a trial can have a remedial or prophylactic 
target... Remedial targets have been the ones for which 
randomized controlled trials have been particularly 
successful. In a study of remedial therapy, the patients 
under investigation are relatively homogeneous because they 
all possess the same target to be altered; the target can be 
directly "measured" and observed for change; the change 
usually requires only a relatively short time to occur; and 
the compared differences in the measured changes can be 
statistically significant without requiring massive numbers 
of patients.'" But "prophylactic trials, designed to assess 
relative efficacy in preventing some future adverse 
occurrence, by contrast, 'are the ones that have been 
notoriously expensive and that have often created, rather 
than clarified, controversy.'" (Robert J. Levine, Ethics and 
Regulation of Clinical Research, Yale University Press, 1986, 
Chapter 8, "Randomized Clinical Trials," section on 
"Excessive Reliance on Randomized Clinical Trials," quoting 
from A. R. Feinstein, "An Additional Basic Science for 
Clinical Medicine: II. The Limitations of Randomized Trials. 
Annals of Internal Medicine, 1983, volume 99, pages 544-550.) 
Note that in AIDS, all "efficacy" trials have been the 
"prophylactic" kind, comparing how well the different 
treatments prevent an endpoint which the patients do not have 
when the trial begins. Symptom reduction would allow the 
"remedial" kind of endpoint to be used in testing efficacy of 
AIDS treatments.

Arguments Against Symptom Reduction As Outcome Measure

* Objection: Symptom-reduction trials do not tell us what we 
need to know. The real goal of confirmatory trials is to tell 
us how the long-term benefit of the treatment, especially 
survival benefit, compares with its long-term harm. Short-
term symptom relief does not give us this long-term 
information.

* Reply: There is no way around the fact that long-term 
information takes a long time to obtain. The practical result 
is that long-term trials with fixed protocols cannot be run 
successfully, because treatments are changing rapidly, 
protocols become undesirable before a long-term trial can 
finish, and there is no way to keep people on inadequate 
treatment long enough for the body counts to be obtained. And 
besides the human cost of having to wait years for the 
information -- often a separate wait for each drug or 
combination regimen tested -- there is also the scientific 
cost of having to wait years for each "turnaround" (for what 
is learned from the results of one trial to be available for 
use in the design of another).

There is a saying that the best can be the enemy of the good. 
We must use practical judgment to move ahead where we can, 
instead of being paralyzed by the lack of a path to perfect 
knowledge.

* Objection: Symptoms in HIV disease are highly individual. 
Exactly which symptoms would one use as indicators of drug 
effects?

* Reply: This question needs research -- through study of 
case histories and of clinical-trial data, and perhaps 
through pilot studies. But there have been major, dramatic 
symptom improvements, when viral load and CD4 counts have 
shown that an antiviral treatment has been particularly 
successful. Symptoms often respond strongly to effective 
treatment. It would be surprising if no useful symptom-based 
indicator of treatment success could be defined.

* Objection: Symptom information is likely to be burdensome 
to collect in clinical trials, and is often biased. 

* Reply: Symptom information is burdensome and biased when 
trials collect too much data, on the chance that something 
might be useful later. But a symptom-reduction trial can take 
a more focused approached. Only one or at most a few symptoms 
need be recorded. These symptoms can be selected to reduce 
bias, recording instruments can be fine-tuned, and observers 
can be trained. And everyone has the symptom at entry into 
the trial, providing a baseline for comparison.

* Objection: Early in the epidemic, some symptoms were found 
not to predict progression to AIDS.

* Reply: All cases of failure of symptoms to predict disease 
progression need to be reviewed in detail. What happened 
then, and what can we learn from it today?

But early experience must be applied cautiously in the 
present. Several years ago, it was widely believed that due 
to immune damage, people with CD4 counts under 200 -- 
certainly under 100 -- could not improve much by any 
antiviral treatment alone, no matter how effective it was 
against the virus. But now there are cases of CD4 count going 
from under 100 to several hundred with only antiviral 
treatment -- and simultaneously most or all HIV-related 
symptoms going away. The difference reflects better 
antivirals, and more choices of treatment for patient 
management. The only antiviral available years ago -- AZT 
monotherapy -- has very limited effectiveness. What happened 
in the past should not automatically be applied today, 
especially if it stops us from developing opportunities 
available now.

Also, note that the development of a symptom during disease 
progression is different from the rapid resolution of that 
symptom due to antiviral treatment. Even if symptom 
development fails to predict later disease outcome, symptom 
resolution after therapy must still be investigated 
separately.

* Objection: If the symptoms take a long time to resolve, you 
could miss an important drug.

* Reply: Case reports suggest that many symptoms improve 
rapidly and dramatically when viral load falls greatly due to 
successful antiviral treatment. Trial designers can avoid 
choosing indicator symptoms which do not change rapidly.

* Objection: These trials cannot test drug benefit on people 
who are completely asymptomatic. Will they be excluded from 
the drug indications?

* Reply: No. These trials use indicator symptoms to 
demonstrate an underlying benefit -- which, if it exists, is 
unlikely to go away just because there are no symptoms to 
show it immediately. Drug indications must be based on all 
available knowledge -- including viral load and T-helper 
count changes, which usually can be observed in 
asymptomatics.

* Objection: Symptom reduction may be a useful outcome 
measurement for immune-based, anti-pathogenesis, or certain 
miscellaneous therapies, where no validated endpoints are 
available. But for antivirals, it has no advantage over viral 
load, which directly measures the effect being sought.

* Reply: Some people still have doubts that viral load 
reduction caused by a drug will translate into concrete 
clinical benefit for patients. The symptom reduction outcome 
addresses this specific concern. In other respects, for 
testing antivirals, viral load may be superior, because it is 
further along on the development curve. And of course viral 
load can be used as an additional outcome measurement in a 
symptom-reduction trial.

* Objection: Symptom-reduction trials are likely to be 
rejected on various grounds. And by proposing them, one will 
be seen as buying into the position that clinical 
confirmation is needed for each treatment or combination 
which has received accelerated approval.

But AIDS is different from other diseases. There is 
tremendous individual variation -- and a virus which may be 
able to mutate against any treatment. In this situation, we 
need to build an armamentarium of active treatment options, 
so that when one treatment does not work for a patient, 
others will be available. The idea that every treatment must 
have clinical confirmation, even after good safety and viral 
load response have been shown, is entirely inappropriate to 
the AIDS situation, and is a major obstruction. We should be 
telling those who insist on such confirmation that the 
emperor has no clothes, that they are wrong.

* Reply: We proposed symptom reduction for two reasons. 
First, it has certain intrinsic advantages as an outcome 
measure, especially for testing experimental treatments other 
than antivirals. But also, the demand for death or 
opportunistic infection endpoints is politically so strong 
that it may be impossible to move forward unless a compromise 
can be found. Symptom reduction goes part way. It is a 
clinical measurement of real benefit, not a blood test. But 
it is largely a short-term measurement, not a long-term one.

There are many reasons why the death and opportunistic 
infection endpoints have strong support. First, drugs have 
been approved in the past without enough guidance on how to 
use them; often doctors and patients do not even know if an 
approved treatment will extend life or shorten it. Also, many 
people believe that it is morally wrong to market a drug 
which has not been proven to have benefit; and they see any 
shortcut to such proof as weakening standards of science and 
public protection, and letting big corporations rake in 
profits without doing their job. And many believe that taking 
the time now to get the science right will serve the greatest 
good of the greatest number eventually. Some want their 
expected death to be meaningful in this way, as a service to 
others in the future.

Clearly some of the issues in the clinical-trials debate are 
pragmatic -- which course of action will actually lead to 
faster progress and better treatments, both in the near 
future and the far future? Other parts of this dispute are 
moral in nature, and therefore less subject to verbal 
resolution. The best outcome may be a compromise both sides 
can accept.

This dispute is not new, but has roots in long-standing 
conflicts in clinical-trial design. Feinstein and Levine 
(references above) sketched differences between "pragmatic" 
trial designers (usually clinicians), and "fastidious" ones 
(usually biostatisticians). We suspect that this conflict may 
be partly rooted in personality differences, which may be 
with us indefinitely -- not just technical beliefs, which 
would tend to resolve as technology develops.

And we cannot ignore institutional incentives. Large, long-
lasting trials provide predictable income streams and 
staffing demands, suitable for long-range planning by large 
medical institutions; small, rapid trials are harder to plan 
for. And very expensive drug development favors large 
companies, which can meet any costs demanded; in return they 
receive a monopoly -- in effect, an important form of capital 
for the large companies -- as smaller and potentially more 
efficient companies are excluded from drug development unless 
they sell out to large companies on their terms. In these 
ways, marginally unworkable standards for drug development 
are potentially worth billions of dollars to key institutions 
-- a massive institutional incentive which cannot fail to 
affect what is or is not funded, published, approved, and 
eventually accepted into mainstream medical care.

Symptom Reduction As Outcome Measure: Summary of Advantages 
Over Disease Progression, in HIV Efficacy Trials

* Symptom reduction measures a clinical benefit to patients, 
not just a blood-test value. Since the trial designers choose 
an indicator symptom not directly affected by the treatment 
being tested, this particular symptom serves as a marker for 
a broader systemic improvement.

* Trials can be run in a few weeks, because many HIV-related 
symptoms do respond to a powerful antiviral within that time. 
There is no need to wait for disease progression in the 
control group.

* Trials can be small, because every participant produces a 
measurement -- not just the fraction who reach an endpoint, 
as in disease-progression trials.

* Because these trials last only for weeks, and participants 
are not gravely ill, compliance will be better than with 
trials which last so long that the standard of care overtakes 
them. The dropout rate should be much lower than for disease-
progression efficacy trials.

* Volunteers need not have very advanced illness; therefore, 
it will be feasible to recruit therapy-naive patients when 
necessary for scientific reasons.

* The fact that these trials are small and very rapid, and 
then release results for everybody, will reduce pressure to 
include additional patients in order to provide treatment 
access for them.

* These trials can easily be randomized and double blind. 
Therefore, any subjectivity in the rating of symptoms should 
not cause a consistent bias.

* Placebos can be used when needed, because trials are short, 
and symptoms can be selected to be not immediately dangerous 
or severe.

* Symptom-reduction trials can measure the efficacy of 
antiviral, immune-based, pathogenesis-oriented, supportive, 
or other kinds of therapy -- all with an identical trial 
design if desired. This facilitates testing combinations of 
these different kinds of potential treatments.

How can we use the upcoming FDA workshop on confirmatory 
trials to open a national discussion on allowing improvement 
of existing symptoms -- not just prevention of death or AIDS-
defining opportunistic infections -- as a measure of drug 
efficacy? We want the professional community to fairly 
consider this kind of design, and accept or reject it on its 
merits. If it is accepted in the professional consensus, then 
researchers could get funding for such trials, and the FDA 
would let sponsors know that it could accept the results as 
definitive proof of efficacy.

[Note: Our last issue announced the FDA workshop on the 
design of HIV clinical trials, September 6-7, with an 
advisory committee meeting on September 8; both meetings will 
be held at the Natcher Auditorium of the National Institutes 
of Health in Bethesda, Maryland. The workshop will focus on 
"confirmatory" efficacy trials (for drugs which have already 
received accelerated approval). These meetings are open to 
the public, but advance registration is recommended, and to 
be sure of seating, persons should arrive early even if 
registered; 300 people have registered as of August 16, and 
the auditorium holds 500. To register, send a fax to Heidi 
Marchand or Kimberly Miles, Office of AIDS and Special Health 
Issues, 301/443-9216; include your name, organization if any, 
address, and phone number. For more information, call Heidi 
Marchand or Kimberly Miles, 301/443-0104.

[AIDS TREATMENT NEWS will attend, and is seeking professional 
and community support for getting the trial-design 
suggestions outlined above "onto the table" for 
consideration, at these meetings and otherwise.]


***** FDA Warning on Raw Oysters

The FDA has issued a warning that persons with HIV, or with 
liver disease, or with certain other medical conditions, 
should avoid eating raw oysters because of the risk of 
infection with the bacterium Vibrio vulnificus. The risk is 
especially great in oysters from the Gulf of Mexico, 
especially during warm months, April to October. Forty 
percent of infections with Vibrio vulnificus  are fatal, 
often within two days. This bacterium is not a threat to most 
healthy people.

Because Vibrio vulnificus occurs naturally, not as a result 
of pollution, eating oysters from reputable sources does not 
provide protection. Proper cooking completely kills the 
bacteria and eliminates the risk.

For more information, or copies of a brochure, call the FDA 
Seafood Hotline, 800/FDA-4010.


***** ICAAC Conference, September 17-20, in San Francisco

The 35th Interscience Conference on Antimicrobial Agents and 
Chemotherapy, an annual conference focusing on new 
antibiotics and antivirals, will be held in San Francisco 
September 17-20. A number of talks and poster presentations 
will be relevant to HIV disease, including results of a major 
trial of d4T.

While most presentations at ICAAC are not AIDS related, this 
meeting has become a major conference for new scientific 
information about AIDS -- especially this year, since the 
International Conference on AIDS now meets every two years 
and will not meet in 1995.

Registration for ICAAC is $290 ($225 for members of the 
American Society for Microbiology, the conference sponsor); 
press can register without charge. For more information 
contact the American Society for Microbiology, Meetings 
Department, 202/942-9248, fax 202/942-9340.

Note: A separate but coordinated conference of the Infectious 
Diseases Society of America will be held just before the 
ICAAC conference, September 16-18, at the San Francisco 
Hilton and Towers. This meeting consists mainly of lectures 
by leading physicians to physicians, and usually includes 
several talks on AIDS and related topics, such as 
tuberculosis. For more information, call IDSA, 202/857-1139.


***** Merck Protease Inhibitor Note: Expanded Access Program 
Registrants Should Receive, and Return, Mailed Confirmation

Persons who registered for the Crixivan (Merck protease 
inhibitor) program (see AIDS TREATMENT NEWS #227, July 21, 
1995; registration for the initial selection closed August 
11) should make sure they receive the one-page patient 
qualification form, which must be filled out and faxed or 
postmarked by September 8. In one case we know, several 
patient records were temporarily lost due to an electrical 
storm which crashed the computer while the records were being 
entered. Fortunately the health-care worker who called to 
register those patients recognized the problem when the 
qualification forms for the patients who had been entered 
just before the crash were not received in the mail; a phone 
call confirmed that the computer had no record of those 
people, and they were re-registered. Anyone else who had the 
computer go down while they were entering records should be 
especially careful to check that everyone they entered is 
known to the system.

If you registered but have not received the mailed 
qualification form, call the Crixivan program at 800/497-
8383.

Also, do not wait for the last day to fax the qualification 
form. In another expanded-access program, AIDS TREATMENT NEWS 
heard from people who missed the deadline because the fax 
lines were continually busy on the final day.


***** Alternative Medicine and HIV/AIDS: Request for 
Applications

Bastyr University's AIDS Research Center will award two to 
five grants, totaling $105,000, "for the investigation and 
evaluation of promising therapies currently in use for 
treating people with HIV or AIDS." Applicants should obtain a 
copy of the RFA (Request for Applications), send a letter of 
intent as soon as possible, and must submit their proposal by 
the deadline, Tuesday, October 3. Grants should be awarded on 
January 15, 1996.

The AIDS Research Center was established in October 1994 by a 
grant from the Office of Alternative Medicine of the U.S. 
National Institutes of Health. Its mission is "(1) to 
describe forms and patterns of use of alternative medical 
therapies for the treatment of patients with HIV infection 
and acquired immune deficiency syndrome (AIDS), and (2) 
evaluate effectiveness of alternative therapies for the 
treatment of HIV/AIDS from five program areas of alternative 
medicine: nutrition, traditional and ethnomedicine, energetic 
therapies, pharmacological and biological therapies, and 
bioelectromagnetic medicine."

For information or a copy of the RFA, contact Cherie Reeves, 
Project Coordinator, 206/517-3578.


***** San Francisco: AIDS TREATMENT NEWS Needs Office Space

AIDS TREATMENT NEWS is looking for office/residential space 
in San Francisco. We need at least a two-bedroom flat where 
it is OK for several people to work during the day; 
alternatively, we could use two studio apartments in the same 
building. We also need access to public transportation, and 
affordable rent.

If you know of suitable space, call us at 415/255-0588, 10 
a.m. to 4 p.m. Monday through Friday.


***** House Moves to Block Internet Censorship

by Bruce Mirken

In a move that may bode well for AIDS educators and 
activists, the House of Representatives acted in late July to 
block Senator James Exon's (D-NE) "Communications Decency 
Act."  Exon's measure, an amendment to the telecommunications 
deregulation bill, contained sweeping language barring 
"obscene," "indecent" or "harassing" communications online or 
via phone or fax.  Observers feared it would block online 
distribution of AIDS prevention information as well as bar 
activist phone/fax "zaps" of drug company and government 
officials. (See AIDS TREATMENT NEWS #227, July 21, 1995, for 
a detailed discussion of the amendment's implications.)

Exon's measure breezed through the Senate, but the House -- 
perhaps spurred by Speaker Newt Gingrich's opposition to the 
Exon amendment -- took a directly opposite tack.  It voted 
420 to 4 to add to its version of the telecommunications bill 
an amendment sponsored by Reps. Christopher Cox (R-CA) and 
Ron Wyden (D-OR) specifically designed to counter Exon.  The 
Cox-Wyden amendment would protect from liability any online 
service (such as Prodigy or America Online) that voluntarily 
restricts access to materials considered obscene or 
objectionable while specifically barring the Federal 
Communications Commission from regulating the Internet or 
online services.

Complicating things, though, is an additional amendment 
successfully offered by Rep. Henry Hyde (R-IL) that would 
modify obscenity laws to "criminalize some forms of online 
speech," according to a WASHINGTON POST account.  The 
apparent conflict between the two amendments as well as the 
clear conflict between the House and Senate bills will have 
to be resolved in a House-Senate conference committee.  The 
date for that meeting and the membership of the conference 
committee will be determined after Congress reconvenes in 
September.


***** Is NIH AIDS Research in Danger?

by Bob Roehr

In July the House Appropriations Committee eliminated the 
separate line item for AIDS research at the National 
Institutes of Health, and with it the authority of the Office 
of AIDS Research to control the NIH AIDS budget. The Senate 
will deal with the matter in September. 

This action does not necessarily reduce funding for AIDS 
research, at least not immediately, because the money in the 
line item comes from recommendations made by NIH, which can 
spend the same money whether or not it is broken out 
separately in the budget. But many leading AIDS researchers 
and advocates view the elimination of the OAR's budget 
authority as a serious long-term threat to the coherence and 
rational planning of the NIH AIDS research program - which is 
by far the world's largest. 

Background

AIDS research grew piecemeal within each of the 24 Institutes 
of the National Institutes of Health until creation of the 
Office of AIDS Research (OAR) in 1988 to coordinate those 
disparate efforts. 

A number of observers, scientists and especially the New York 
activist Treatment Action Group (TAG) in their July 1992 
"Critical Review," pointed to lingering deficiencies with 
that structure. 

HIV research was then approximately 10 percent (now 12 
percent) of the NIH budget. The NIH "culture," the 
traditional way of structuring research, suggested creation 
of a separate Institute for AIDS. But the nature of HIV 
disease, with its multitude of associated diseases affecting 
various organ systems, pointed to a broader approach, recalls 
Derek Hodel, who coordinated research and treatment issues 
for the AIDS Action Council in Washington at the time of the 
NIH reorganization, and now does similar policy work with the 
Gay Men's Health Crisis in New York.

The NIH Revitalization Act of 1993 dealt with many of these 
issues by creating what some call "an Institute without 
walls." It gave statutory authority to the Office of AIDS 
Research, which previously had been an administrative 
creation. It charged OAR with developing a strategic plan to 
coordinate research. And most importantly, it gathered 
together all funding for NIH AIDS research under a 
consolidated line item budget. Under this system, which is in 
force today, OAR coordinates the overall NIH AIDS research 
program. Its role is limited, however, in that it does not 
review individual grants.

There was and continues to be resistance to OAR from some 
Institute Directors who resent sharing control of portions of 
their budgets. 

Noted immunologist William E. Paul, M.D., was hired from 
within NIH by Director Harold Varmus, M.D., as the first full 
time Director of OAR. He began work in February 1994.

Surprise in Congress

Labor/Health and Human Services Appropriations Subcommittee 
Chair John Porter (Republican, Illinois) proposed a budget in 
early July which eliminated the OAR line item for NIH. At the 
same time he increased total NIH funding by $600 million, or 
5.7 percent, an unheard of increase in light of the deep 
slashing to other federal programs.

The proposal caught AIDS lobbyists by surprise. They tried to 
restore the status quo in the subcommittee through an 
amendment by Nancy Pelosi (D-California) but lost 8-5 on a 
party-line vote. 

Critics were somewhat mollified by the committee report, 
offered by Porter and modified by language which he accepted 
from Pelosi, which stated their continued strong support for 
OAR. Nonetheless they are pushing for the Senate to maintain 
separate budgetary authority and for acceptance of that 
position in conference between the two bodies.

"The Congressman's rationale here is that politicians should 
not make decisions abut specific amounts to be earmarked for 
each disease," said Porter spokesman David Kohn. He is trying 
to "shield" and "depoliticize" AIDS research from attacks by 
the likes of Senator Jesse Helms. 

Most of those who criticize Porter's action go out of their 
way to praise his intent and motivation. But they see 
inconsistencies in the argument and fear the real long term 
impact on AIDS research at NIH. 

To AmFAR's public policy director Jane Silver, "It is a bit 
misleading to say that they want the scientists to decide," 
since Varmus is not getting discretionary authority over the 
entire $11 billion budget. She points to the separate line 
items for the 24 Institutes, "Why aren't they (scientists) 
deciding about cancer? Why aren't they deciding about heart, 
lung, and blood? How come they are just deciding about AIDS?" 

"These steps will not only shatter the federal AIDS research 
effort into 24 pieces," said her boss, AmFAR chair Mathilde 
Krim, Ph.D., "but will leave it without either a guaranteed 
overall funding level or strategic planning or coordination."

TAG's policy director, Mark Harrington, called it "a frontal 
assault on AIDS research programs... threatening to make NIH 
AIDS research less efficient, more wasteful, and 
unproductive."

"You don't make policy without budgetary control," said 
Winnie Stachelberg, senior health policy analyst with the 
Human Rights Campaign Fund (HRCF), who previously worked at 
the Office of Management and Budget. "If you don't control 
the dollars, if you don't have a stick with some authority, 
then you don't have the ability to implement a strategic plan 
and to find a cure." 

"Without the individual earmarks for AIDS funding... research 
could be whittled away and gradually deteriorate," feared 
Mark Barnes, executive director of the AIDS Action Council.

"In 1986-87 there was all this money going into a black hole 
at NIH. Not only was it not getting us anywhere, but no one 
even knew where it was being spent. That was why OAR was 
given strategic responsibility," said Gary Rose, lobbyist 
with AIDS Action. "This puts us back to not being able to 
follow any paper trail until long after it is going to do us 
any good." 

He sees "the old boy network completely intact at NIH" and 
fears that dropping OAR will result in closing the process to 
"community people and extramural scientists... and the 
virologists won't talk to the immunologists any more because 
there won't be anything in it for them to have that 
conversation."

More than 200 AIDS researchers signed an April letter 
expressing "strong support" for OAR. Several dozen quickly 
signed on to a subsequent letter warning that the 
subcommittee action, "unless overturned, would do grievous 
harm to the nation's efforts to eliminate this deadly 
disease." 

It "would effectively emasculate" OAR, read a column in the 
New York Times by David Baltimore, Ph.D., at MIT and David 
Ho, M.D., director of the Aaron Diamond AIDS research center. 
They called the OAR "the rudder that steers us in the right 
direction against the disease." 

Arnold Levine, M.D., Chair of the NIH AIDS Research 
Evaluation Working Group whose report on a top to bottom 
review of all HIV research programs is due this fall, wrote 
to Porter: The single appropriation is the only mechanism 
that "will allow the elimination of unnecessary or outdated 
programs, streamline the research portfolios, and redirect 
limited resources to those areas with greater scientific 
promise for the ultimate prevention and cure." 

"To eliminate the single appropriation (before this work is 
complete) would freeze out the benefits of this evaluation 
process and leave in place the status quo," concluded Levine.

"There is no question that total funding for AIDS will 
probably fall," said Northwestern University researcher John 
Phair, M.D. "This is typical political nonsense. To make 
decisions on the basis of no data is a mistake." 

Mike Shriver with Mobilization Against AIDS is "afraid that 
if you lose OAR you lose behavioral research." He believes 
coordination has "pulled researchers out of the microcosm and 
put them into the macrocosm" of real life behavioral 
questions surrounding prevention education and lifestyle 
modifications.

Silver believes the priorities and working relationships of 
Varmus and Paul would minimize immediate impact of the House 
actions, should they survive. "But you don't know how long 
those individuals will be there." She wants to see a policy 
in place that will survive the people. "You don't build sound 
policy on personalities."

Should there be a separate NIH Institute of AIDS? This latest 
fight over the House action is likely to renew interest in 
that question. And now, with the entire NIH coming up for a 
five year reauthorization in 1996, is the perfect time to 
debate it.


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