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AIDS TREATMENT NEWS #215, January 20, 1995
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

New Information on HIV Rapid Turnover - What Does It Mean?

Kaposi's Sarcoma: Possible Foscarnet Treatment

1995 Outlook: Research Strategy

Protease Inhibitor Task Force: Opportunity for Participation

KS, DOX-SL: FDA Hearing February 14

FDA Advisory Committees: Hotline for Upcoming Meetings

International Conference for People Living with HIV and AIDS,
Cape Town, South Africa, March 6-10; Pre-Conference for
Women, March 4-5


***** New Information on HIV Rapid Turnover - What Does
      It Mean?

by John S. James

On January 12, many newspapers carried page-one stories about
a major scientific advance in understanding AIDS. Some of the
reporting has been unclear and confusing to readers, however.
This article will outline what the discovery is and why it is
important to people with HIV or AIDS. We will also explain
our concern that this new understanding, while indeed
important, shows signs of being misunderstood in ways that
could seriously harm AIDS research.

The occasion of the recent press coverage was the publication
of two articles and a commentary in the January 12 issue of
Nature,(1,2,3) which is one of the most prestigious
scientific journals. The two articles are by two well-known
research groups which independently arrived at essentially
the same conclusions. AIDS researchers worked with
mathematicians to help them reach a deeper understanding of
the data -- which came from blood tests of patients with
advanced HIV disease as they started taking certain
experimental antivirals in small clinical trials.

The discovery announced in the newspapers on January 12 was
not news to the scientific community, which has heard the
central idea at a number of public conferences during the
last year. We published a preview last November, in an
extensive quote from Douglas D. Richman, M.D., who spoke on
November 12 to a physicians' conference in San Francisco (see
"Viral Load, Small Trials, and Immune Recovery," AIDS
TREATMENT NEWS #211, November 18, 1994).

New Understanding of HIV

The new understanding of how HIV behaves in the body was made
possible by the development of better antiviral drugs, which
can now shut off HIV reproduction almost completely (although
so far only for a short time since resistant virus develops
in a few weeks) -- and also by the new blood tests which
measure plasma HIV RNA, a much more accurate indication than
the old p24 antigen tests of how much virus is in the blood.
The three antiviral drugs used were the Abbott protease
inhibitor (ABT-538), the Merck protease inhibitor (L-524,
also called L-735,524), and Boehringer Ingelheim's nevirapine
(which is a non-nucleoside reverse transcriptase inhibitor);
all three of these drugs are experimental and currently in
clinical trials. AZT, ddI, and other approved anti-HIV drugs
do not stop the virus well enough to make the new discovery
obvious. [Note: the HIV RNA blood tests used are today
available to physicians; for background, see "HIV RNA: New
Blood Tests for Individualized Therapy and Faster Trials,"
AIDS TREATMENT NEWS #204, date August 5, 1994, and later
issues.]

Both the research teams measured the HIV RNA frequently (at
least weekly) when patients started taking the new
experimental antivirals. They found that once the
reproduction of new virus was shut off, the viral level in
the blood declined very rapidly; about 30 percent of the
virus is cleared from the blood each day (and this percentage
may be about the same regardless of stage of the disease).
Since blood levels are fairly stable from day to day when the
patient is not taking an antiviral, about as much new virus
must be produced every day as is destroyed. The essence of
the new discovery is that the "turnover" of new virus in the
body is far more rapid than people had believed -- in just a
few days, most of the virus in the blood has been removed and
replaced with fresh virus.

Also, these drugs work by stopping the infection of new cells
-- not by shutting off viral production from chronically
infected cells -- and still they often cause the amount of
virus in the blood to drop by 99 percent or more. This means
that almost all of the enormous amount of virus being
produced continuously during HIV infection is coming from
newly infected cells.

The researchers also measured the recovery of CD4 cells (T-
helper cells) while the reproduction of HIV was temporarily
shut off. They found that CD4 cells increased very rapidly
during this time. This seems to mean that they are also being
destroyed equally rapidly when the virus is not shut down.
(Although an alternative possibility, which we do not believe
is ruled out by the new Nature articles, is that active HIV
infection produces something that suppresses production of
new CD4 cells; if this is the case, CD4 cell turnover in HIV
disease may be less than now thought.)

[Note on terminology: Until now AIDS TREATMENT NEWS has
preferred the term "T-helper cell" to "CD4 cell," as being
better for communicating with the public. But now the more
accurate term "CD4 cell" (or "CD4+ cell," which is the same
thing) is coming into wider use, and will be our preferred
usage in the future.]

Through simple calculations based on this data, the
researchers estimated that about 100 million virions
(individual virus particles) are normally being produced and
destroyed each day. (Note that this applies only to patients
with fairly advanced HIV disease, who were studied in this
research; they had a median CD4 count of 102 in one of the
papers, a mean of 180 in the other. In earlier stages of
asymptomatic HIV infection, the number of virions would
usually be much less.) Also, the researchers estimated that
about two billion CD4 cells are also being created and
destroyed each day in these patients. Each infected cell can
produce many copies of the virus; the researchers suspect,
therefore, that most infected CD4 cells are destroyed by the
immune system before they ever have a chance to produce
complete virus.

Importance

These findings are important to people with AIDS/HIV because:

* They strongly suggest that if HIV reproduction could be
largely stopped for a longer time, and kept at a very low
level indefinitely, then the immune system would have much
more ability to recover, even without immune-based treatment,
than most physicians and scientists had believed.

Note that this does NOT mean that the virus will be
eradicated. Huge reservoirs of latent virus will still likely
remain, in the DNA of cells in lymph nodes and elsewhere.
While it is latent, it is not doing damage. But some of the
latent virus may become activated later and re-establish the
active infection. It will probably still be necessary to take
drugs to keep the virus suppressed -- although if the immune
system recovers, it may be an important help in this process.

* It is now clear that researchers can test potential
antiviral drugs and combination treatments in people in
small, rapid trials -- which get results in weeks. This means
that it is feasible to test many new treatments quickly,
greatly speeding the development of better AIDS/HIV
treatments.

Of course it will be necessary to continue testing the
treatments which do show antiviral activity, to see how long
they work before viral resistance develops. This should not
be hard to do, since patients will naturally want to continue
taking a treatment which is working.

Other steps are also necessary before FDA approval. [We
analyze the critical bottleneck in the whole process -- the
need to prove actual clinical benefit to patients -- in "1995
Outlook -- Research Strategy," below.]

* They emphasize again the major problem of HIV developing
resistance to drugs. The very rapid turnover of HIV in the
blood means that in just two to four weeks, the drug-
susceptible viral population in a patient can be replaced by
a drug-resistant population, meaning that the drug will no
longer work, or at least not work as well.

The researchers emphasized the need to use combination
treatments to prevent drug resistance. Drug combinations help
to prevent resistant viruses from developing, because only a
small fraction of the virus will initially be resistant to
any candidate drug. If a second drug is added, only a small
fraction of that small fraction will be resistant to both.
The more drugs that are added to the combination, the less
likely it will be that any virion will be resistant to all of
them. But with billions of virions in the body, it may take a
number of drugs in combination to stop all of them.

Some researchers have suggested that combination treatments
should be used early in infection, when the viral load in the
body, and also the variation of the virus, is less. (It is
generally believed that HIV infection starts with only one
variant of HIV, but as the disease progresses, this one
strain evolves into a great many different "quasispecies"
within the individual patient. In each patient, this
evolution is different.)

Comment: What This Discovery Does Not Explain

The most important unanswered question about HIV disease may
be how it progresses from early, asymptomatic infection to
late-stage illness. For years the immune system controls the
virus to a degree, and blood levels stay relatively low. But
somehow the body gradually loses this ability (in most
people, but not in all), allowing the virus in the blood to
increase by as much as hundreds of times, leading to the
development of AIDS.

Many theories have been proposed to explain how HIV
suppresses the immune system -- including, for example,
direct killing of CD4 cells, and also indirect mechanisms
such as molecular mimicry, cytokine or possibly endocrine
dysregulation, autoimmunity, abnormal apoptosis, loss of CD8
cells, etc. If researchers knew why the immune system
gradually loses its ability to control HIV, then it might be
possible to treat HIV infection by correcting this specific
problem, and keep people healthy indefinitely, perhaps
without the need for antivirals.

We are concerned by indications that some researchers, as
well as medical reporters, may uncritically assume that the
new understanding of HIV also explains how the infection
progresses from the early, asymptomatic stage, to the later
stages of greatly increased HIV levels and clinical illness.
Such a premature conclusion could suppress interest and
research in other potential mechanisms of progression.

The new information recently published in Nature was based
only on studies of persons with advanced HIV infection. And
each patient was studied only for a brief snapshot of time;
there was no long-term data on how infection progresses over
time.

The Nature papers do not claim to have shown how HIV
infection progresses. But they are often being implicitly
interpreted that way. Some of these interpretations do not
stand close scrutiny:

* One assumption is that, due to the great number of CD4
cells infected and destroyed, the immune system eventually
becomes exhausted and unable to keep up, and then the disease
progresses because the body cannot produce enough CD4 cells
to replace those that are lost.

But this theory ignores the fact that HIV disease progression
occurs also at earlier stages, when the level of HIV
infection and destruction of T-cells is a small fraction of
what the body will be able to keep up with later. For
example, there is data showing that in persons with a CD4
count around 200, the level of virus in the blood may be ten
to a hundred times more than the level when the CD4 count is
500.(4) How could this exhaustion theory explain the
progression from a CD4 count of 500 to 450 or 400, if at 500
the body still has at least ten to a hundred times the
capacity needed to replace the cells which are lost at that
stage?

* Another assumption -- seen repeatedly in the January 12 New
York Times article -- is that HIV infection progresses
because the virus has a "slight statistical edge" over the
immune system, leading to its eventual victory. But this
theory is unlikely to hold up to an analysis of the dynamics
of stability vs. instability. The levels of both the opposing
sides in the battle -- the virus, and the CD4 cells -- can
change greatly in a time frame of days or weeks. It seems
unlikely that these two opposing forces, which each can
change in days, will just happen to stay approximately
balanced for the much longer time period of years that it
takes for HIV disease to progress.

To visualize the problem, imagine an acrobat on a high wire
who momentarily loses balance, and fights in an attempt to
regain it. Usually only seconds will pass until either
balance is regained, or the acrobat falls off. We do not
expect to see the struggle go on for ten years.

In other words, some mechanism other than a slight
statistical edge must be controlling the timing of HIV
disease progression. No one knows what sets this clock; it
should be a central goal of AIDS research to find out. The
statistical-edge theory, by giving false confidence that the
answer is already known, could distract research from this
key goal.

Note that in most viral and other infections, the dynamics of
the interaction between the replicating organism and the
immune system does not lead even temporarily to a
homeostasis, to a balance or steady state. Instead, the
immune system either eradicates or almost eradicates the
disease-causing organism, or the infection progresses until
the person dies. (Nor does the limited supply of cells to
infect explain the limited growth of HIV, except perhaps at
end-stage illness; at earlier stages, the supply of CD4 cells
would clearly allow more viral growth, as shown by the fact
that viral levels will substantially increase later, when
there are fewer such cells available.) No one knows why HIV
reaches a certain blood level and then stops (until the level
changes over months or years). When we discover the mechanism
by which this control becomes established and maintained, but
then gradually lost, we will very likely have a new way of
controlling HIV disease.

* One of the recent Nature articles(1) noted, "The difference
in lifespan between virus-producing cells and latently
infected cells (PBMCs) suggests that virus expression per se
is directly involved in CD4+ cell destruction. The data do
not suggest an 'innocent bystander' mechanism of cell killing
whereby uninfected or latently infected cells are indirectly
targeted for destruction by adsorption of viral proteins or
by autoimmune reactivities."

We are concerned that readers may take away from this
statement something different from what it actually says.
While the data cited may not support indirect mechanism for
the decline of CD4 cells, they do not rule out such
mechanisms, either. Again, our concern is that important
research could be prematurely downgraded or closed off, due
to the rush of enthusiasm which has greeted the new findings.

(And if it turns out that active HIV infection somehow
suppresses development of new CD4 cells, or suppresses their
release into the blood -- and CD4 counts increase rapidly
when the infection is stopped, not because they are usually
being created and destroyed that fast, but because the
suppressive effect is removed -- then the whole issue of the
turnover and lifespan of infected CD4 cells will have to be
rethought.)

Research Strategy Summary

The most important impact of the new understanding of HIV
disease, published in two articles and a commentary in the
January 12 Nature, will be on the strategy of research and
development of new AIDS treatments. We see the following
consequences:

* The new work validates the use of small, rapid screening
trials, in a few patients, to learn which potential drugs
have antiviral activity in people.

* It also shows that if the virus can be suppressed
completely enough, the immune system has much more ability to
recover than many had suspected.

* It also confirms the belief that overcoming drug resistance
is likely to be the biggest challenge to making anti-HIV
treatments work.

* On the minus side, possible misinterpretation of the new
findings (in the current atmosphere of great attention and
enthusiasm for them) may impede important work of learning
how HIV infection progresses -- work which could lead to a
completely different class of treatments which do not attack
the virus directly, but preserve the immune system's ability
to control it.

References

1. Wel X, Ghosh SK, Taylor ME and others. Viral dynamics in
human immunodeficiency virus type 1 infection. Nature.
January 12, 1995; volume 273, pages 117-122.

2. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, and
Markowitz M. Rapid turnover of plasma virions and CD4
lymphocytes in HIV-1 infection. Nature. January 12, 1995;
volume 273, pages 123-126.

3. Wain-Hobson S. Virological mayhem. Nature. January 12,
1995; volume 273, page 102.

4. Phillips AN, Sabin CA, Elford J, and others. Viral burden
in HIV infection. Nature. January 13, 1994; volume 367, page
124.


***** Kaposi's Sarcoma: Possible Foscarnet Treatment?

by John S. James

Foscarnet (Foscavir) is an antiviral used to treat CMV
(cytomegalovirus) infection; it is also used in serious cases
of acyclovir-resistant herpes simplex. It is active not only
against CMV (which is a member of the herpesvirus family) and
herpes simplex, but also against all other known
herpesviruses; in addition it has some anti-HIV activity,
although it is not generally used as an anti-HIV treatment.
Foscarnet is often the initial choice of anti-CMV treatment
in Europe, while ganciclovir is usually the initial choice in
the United States; this difference appears to be due to
historical reasons, as foscarnet was developed by Astra, a
Swedish company, while ganciclovir was developed in the U.S.
Foscarnet must be given intravenously with an infusion pump,
and can cause many serious side effects -- especially kidney
toxicity, which occurs to some degree in many patients
treated; the drug must be used by a physician who has
experience with it. Another disadvantage is that the drug is
very expensive.

Until recently there was no reason to think that foscarnet
would have any use in treating Kaposi's sarcoma (KS). But
last year a laboratory study, published in December 1994,
found evidence that KS might be caused by a previously-
unknown herpesvirus(1) (see AIDS TREATMENT NEWS #213,
December 23, 1994). And another article, also published in
December 1994,(2) reported on a pilot study of five patients,
which was conducted after physicians noticed that KS
regressed in two patients who were treated with foscarnet for
other purposes. Three of the five patients in the pilot study
had a long-term remission of KS, after a single 10-day
treatment (or in one case, two 10-day treatments) with
foscarnet; the lesions disappeared slowly over several
months. In the other two patients, the disease progressed
despite the treatment. KS regressions without treatment are
fairly rare. (These five cases were the ones reported at the
recent conference in Glasgow, Scotland, as mentioned in AIDS
TREATMENT NEWS #213.)

The five patients in the pilot study had low CD4 (T-helper)
counts (24, 26, 270, 6, and 24) when treatment began. The two
who progressed had ongoing, active opportunistic infections
at the time; the three who had long-term regression did not.
All five were also being treated with AZT following the
course of foscarnet.

We talked to Linda Morfeldt, M.D., Dr. Med. Sc., of the
Karolinska Institute in Sweden, who organized the pilot
study. She said that the results so far suggest:

(1) The effect of foscarnet on KS is not proven; however,
other small studies are now being designed to confirm or to
rule out the early findings;

(2) The researchers suspect that the drug may be effective in
relatively early KS which is confined to the skin and mucous
membranes (even if the CD4 count is low) -- but not
effective, or less effective, in advanced KS; and

(3) Patients who also have ongoing active infections, such as
CMV organ disease, pneumocystis, MAC, or fevers of unknown
origin, may not respond to foscarnet as a KS treatment; but
the KS may possibly respond if the opportunistic infections
are successfully treated first.

AIDS TREATMENT NEWS (December 23 issue) asked our readers to
let us know of any experience of persons with KS who used
foscarnet, regardless of the outcome; so far three people
have contacted us as a result. One had fairly mild KS since
June 1992, but he was still getting new lesions, and those
treated with liquid nitrogen would re-appear. He started
foscarnet for CMV retinitis in mid January; by early March
the KS had mostly disappeared. After six weeks on foscarnet,
there were no new lesions, and those treated with liquid
nitrogen did not return.

Another person, before he started using foscarnet, had about
20 KS lesions; these had been removed successfully with
Velban or liquid nitrogen. Since he started using foscarnet,
no new lesions have appeared.

The third person had only one small KS lesion, which was
removed and biopsied in 1992. For three years since he has
been on foscarnet, and no new lesions have appeared.

Early KS Foscarnet Study Now Recruiting in New York

A 20-patient study of foscarnet treatment for early KS is
planned at New York University Medical Center by Drs. Alvin
Friedman-Kien, Miriam Keltz, Abraham Chachoua, Geoffrey
Chazen, Linda Morfeldt, and others. The goal is to confirm
whether or not foscarnet can have any therapeutic benefit in
treating KS.

To answer this question most effectively, this study is
seeking patients with early KS -- approximately five lesions,
and for no longer than six months, and with no prior
treatment for KS. Also, they must have a CD4 count of at
least 50.

References

1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J,
Knowles DM, and Moore PS. Identification of herpesvirus-like
DNA sequences in AIDS-associated Kaposi's sarcoma. Science.
December 16, 1994; volume 266, pages 1865-1869.

2. Morfeldt L. and Torssander J. Long-term remission of
Kaposi's sarcoma following foscarnet treatment in HIV-
infected patients. Scandinavian Journal of Infectious
Diseases. December 1994; volume 26, number 6, pages 749-752.


***** 1995 Outlook: Research Strategy

by John S. James

As 1995 begins, we have more opportunities for progress
toward major improvement in AIDS/HIV treatments than ever
before. And we have clear, feasible paths to follow -- of
safe, rapid, low-cost, high-quality treatment trials in
people, to get solid preliminary information on how certain
potential treatments work in practice. Researchers now have
better tools to run these trials than in the past -- and some
of the new tools, especially tests for plasma HIV RNA, are
also available to individual physicians and patients.

Also, we are hearing more cases of unexpected improvement in
people with HIV or AIDS -- sometimes beyond what would be
thought possible. The most dramatic examples are usually from
clinical trials of experimental treatments such as protease
inhibitors. But there are others who are lucky enough to do
quite well with approved treatments or treatment combinations
which happen to work for them. And some do well with
"alternative" treatments, or their own combinations of
approved, experimental, and/or alternative approaches. We
have long believed that the best strategy available is to try
many different treatments, keeping the ones that seem to work
for oneself, and discarding the ones that seem not to work.

Strategy, Part I: Small, Rapid Screening Trials

These success stories are not the answer, however. They do
not work for everyone, and usually there is no way to predict
who will benefit. Also, no one knows how long the successes
will last -- although often they seem to work for years, with
no evidence of failure in sight.

These success stories, instead, should be seen as treatment
leads, entry points for further research. For each lead,
physicians and scientists should use their best judgment to
try to define a class of patients who might reproducibly
benefit. The next step is to run a small, rapid "proof of
principle" trial -- usually in only a few patients, perhaps
ten to 20 -- looking for consistent changes in measurable
indicators of improvement. There might or might not be a
control group in this trial.

What would happen then? Most of the proposed treatments
tested this way, perhaps 80 or 90 percent, would probably be
found not to work. But there are dozens of good-quality leads
waiting for such a test, and a number of them would come out
with strong support. These would then have the
social/political momentum needed to move rapidly into further
research.

This proposal for many short, rapid screening trials is not
controversial, but is generally accepted as something that
can and should be done. The cost and other resource
requirements would be modest. The problem today is finding
the political and institutional will to make the research
happen.

Strategy, Part II: A New Way to Prove Clinical Benefit

The next step after the screening trials is more
controversial. Those short trials will look for a measurable,
reproducible improvement, usually in blood work. But what
then? Change in a blood test may not prove that the treatment
actually benefits patients. Usually we need other kinds of
trials to show this.

Here we face a serious problem. The prevailing thinking so
far has focused on a kind of clinical-benefit trial design
which will take hundreds of patients for each drug studied,
and take years to produce conclusive answers. This kind of
trial randomly assigns the treatment being tested to some
patients, while others are assigned to standard treatment
instead. Then both groups are observed to see which one gets
sick faster. It takes a long time because AIDS progresses
slowly; even if the new treatment being tested were a
complete, instant cure, the trial might still take years,
because it would have to wait for a statistically significant
number of those on the standard treatment to get sick or die.
And even aside from the time required to run the study
itself, it usually takes years to politic for, finance,
design, organize, and recruit for such a large trial (in
addition to the time to analyze the data, distribute the
results, and get them into standard medical practice). Even
aside from the problem of making people wait for years to get
better treatments, it is clear that there will not be enough
patients available, let alone enough money or trained
researchers, to test more than a few of the treatments which
are likely to pass the small screening trials.

There is a better approach. The treatments which pass the
small screening trials in all probability do benefit patients
-- the difficulty is in finding a feasible way to prove that
conclusively. What we suggest is combining a number of
treatments which work well in the screening trials, until the
cumulative benefit of all of them is great enough to be
clearly visible -- not only in delaying illness, which takes
a long time to see, but also in getting sick people well,
which usually happens much more quickly. When patients
regularly get out of bed and go back about their lives, when
those who were disabled can work again, when chronic
infections disappear with no further need for antibiotics or
other specific treatments, then the value of the AIDS/HIV
treatment will be unambiguous. Statistical proof could be
rapidly obtained, through small, rapid trials (much like the
screening trials) which compare immediate vs. delayed therapy
-- for example, randomly assigning volunteers to either start
the treatment now, or to start it in six weeks. Long-term
followup would of course be included, to make sure that the
benefits last, and to watch for long-term side effects.

This research strategy offers definitive proof of clinical
benefit in small, rapid, inexpensive trials -- instead of the
huge years-long trials that are usually believed necessary to
prove clinical benefit. It may not prove the benefit of each
individual treatment -- only of a certain, partly-arbitrary
combination. But the information available today suggests
that this strategy could quickly provide relief and save
lives; those who want more refined information could pursue
it later.

This approach to proving clinical benefit, unfortunately, is
not yet part of the ongoing conversation on how to improve
AIDS research. We have never heard it discussed or proposed
anywhere. Hopefully our readers will help to get this idea
onto the table, to be considered professionally and accepted
or rejected on its merits. None of the alternatives offers an
acceptable outcome.

This proposal for proving clinical benefit turns the small,
rapid screening trial into part of a complete strategy for
going from where we are now to where we need to be to save
lives. Let's further develop and improve this strategy, and
use it as an organizing tool to get the research done.

Strategy, Part III: New Mechanisms of Action

A third potential research strategy would seek to develop
treatments which control HIV through new, previously-unknown
mechanisms of action.

This could be done through intensive research into what might
be called mystery treatments -- accidental or lucky
discoveries of drugs or other treatments which seem to be
helping in some way, but which have no known mechanism of
action. Mystery treatments may include prescription drugs
(one possible example is sulfasalazine), certain nutrients
(see "Some Vitamins Associated with Decrease Risk of AIDS and
Death," AIDS TREATMENT NEWS #214, January 6, 1995), or other
approaches such as exercise. The goal is not so much to
develop these treatments themselves, as to discover how they
might work. If a new mechanism of action is found, then a
whole new approach to AIDS treatment would become possible.

The key is to direct more research attention and resources
into investigations of mystery treatments, which could lead
to potentially major advances in understanding and treating
HIV disease. This is the opposite of what happens now, which
is that potential treatments without a known mechanism of
action are largely ignored.

How does one begin to study a possible treatment with no
known mechanism of action? One way is to look for consistent
changes in any of the virological, immunological, and other
tests which are available. Any repeatable, predictable
treatment effect could serve as a lead or clue. And of course
this research would be done in collaboration with
specialists, usually outside the AIDS field, with expertise
in the treatment being studied; they can help to identify and
evaluate research leads.

Political Strategy: Organizing National Will

AIDS research and AIDS prevention have always suffered from a
lack of full national commitment to AIDS. Today this problem
is becoming more critical than ever before. As it affects
research, it takes many forms:

* AIDS research has long overemphasized large, high-tech,
complex, and product-oriented projects, because those are the
ones people get paid to do, the ones that build a politically
powerful constituency (lobby). Corporate research is almost
always oriented toward proprietary products; in theory,
government and foundation research should fill in the gaps by
doing necessary work which companies will not do -- including
basic research, and also including the small trials that we
suggested above, for those treatment leads which are not
products that corporations will study. But due to conflict of
interest, revolving-door employment, and increasing reliance
by academic institutions on entrepreneurial funding, non-
corporate institutions have not adequately set their own
agendas. As a result, academic, government, and foundation
researchers have tended to study the same drugs and
approaches that corporations already are studying, or should
be.

Part of the problem is the ever-increasing difficulty of
making anything happen in clinical research (due to ever-
growing costs and regulatory requirements, as well as
increasing scarcity of funds). This creates a conservative
bias, by making it hard to get any trial off the ground
unless it has a large, pre-existing constituency. Since new
ideas almost never come into being with a large constituency,
they almost always suffer great delays while the necessary
professional/commercial/regulatory momentum develops.

In other circumstances, it would be possible to correct these
structural defects. But due to the widespread attitudes
around AIDS, the nation has not found the will to do so.

* The recent elections have created new and serious problems.
Many members of Congress seem to be interested in
representing only one group of people -- white, heterosexual
men with good incomes -- and have little interest in anyone
else's concerns. (A more accurate statement would be that
they represent the frustrations of certain voters, and the
interests of multinational big business.) Since relatively
few such people have AIDS, money may be taken from AIDS for
tax reduction, military spending, and other rewards for those
who financed the recent political campaigns.

* Recently we spoke with two business reporters not connected
with AIDS, and found a well-developed ideology of fatalism
tailor-made to justify not bothering with AIDS research. One
compared AIDS research to a swamp, in that the farther you go
in, the deeper you get, without end. The other compared AIDS
to the common cold -- more serious, he acknowledged, but
similar in that despite ongoing progress, we do not expect to
ever see a time when people do not get colds (or, by obvious
analogy, a time when people do not die of AIDS).

These images did not come from their personal experience, but
from somewhere else. This ideology does not reflect anyone's
experience, but appears to have been constructed for a
purpose -- to justify abandoning people with AIDS or HIV.

* Other national-will problems are closer to home. AIDS
service organizations have never shown much interest in
research -- and neither has organized medicine. And public-
policy experts, in Washington and elsewhere, seldom
understand science and technology issues, or have any serious
interest in them.

* Also close to home is the lack of popular mobilization on
AIDS. Most people affected by HIV do nothing, ever, to help
the cause of AIDS research. One major reason is that
organizers have not created effective channels for them to
use in doing so. In most locations, the only options, the
only ways to interact with the issue, are to send a check to
a distant national organization -- or possibly to sit through
many hours of high-tension, ego-battle meetings, before the
new person is allowed to actually do anything which
contributes. Many people want to meet with friends and
neighbors to write and call Congress to support AIDS funding
-- perhaps the most important thing they could be doing now
-- but nobody has organized to give them the information they
need.

The public motivation certainly does exist; as we pointed out
in the last issue of AIDS TREATMENT NEWS, at least 50 million
people in the U.S. alone have a relative, friend, or
acquaintance whom they know has AIDS or HIV. What must be
done is to establish a social movement so that these millions
of people can make their voices heard, instead of remaining
silent as is almost always the case today.

In summary, we now have excellent opportunities for progress
in treating AIDS. But they are not being exploited
effectively. Solutions have been identified; it is up to us
to organize and insist that they be implemented.


***** Protease Inhibitor Task Force: Opportunity for
      Participation

The February 23-24 meeting of the National Task Force on AIDS
Drug Development (NTFADD), especially February 23, may be a
pivotal moment in the development of protease inhibitors.
Activists want the NTFADD to appoint an official protease
inhibitor task force which can work effectively to find ways
to make the drugs accessible to patients; to facilitate
research in combination therapies, cross resistance, etc.; to
facilitate collaboration and sharing in research; and to
overcome corporate and regulatory barriers. Note that those
who want to speak at the meeting should make advance
arrangements by February 9 (see AIDS TREATMENT NEWS #214,
January 6, 1995, page 8).

For background on the proposed protease inhibitor task force,
see AIDS TREATMENT NEWS #210, November 4, 1994. If you can
help, call Jules Levin at 718/624-8541.


***** KS, DOX-SL: FDA Hearing February 14

The Oncologic Drugs Advisory Committee will consider approval
of DOX-SL, for persons with AIDS-related Kaposi's sarcoma who
have failed systemic chemotherapy, either because of toxicity
or because of disease progression. This meeting, which is
open to the public, will be at the FDA's Parklawn Building,
in Rockville, Maryland. Persons interested in speaking should
call Adele Sefried at the FDA, 301/443-4695, by February 10.
It is particularly important for physicians or patients with
personal experience with DOX-SL to address the committee.

Later in that meeting, the committee will also consider
approval of Zoladex (goserelin acetate) for palliative
treatment of advanced breast cancer in pre- and peri-
menopausal women.


***** FDA Advisory Committees: Hotline for Upcoming Meetings

You can find out about upcoming meetings of any FDA advisory
committees through a voicemail system run by the FDA.
Information is updated as soon as it becomes available, and
is often more current than meeting notices in the Federal
Register.

To use the voicemail system, call 800/741-8138, or 301/443-
0572.

There are several dozen different advisory committees; you
can select the one you want through the voicemail system.
However, you can save time if you have the five-digit code
for the committee you want, as you can enter the code
immediately and bypass the voice menus. The codes for the
advisory committees most involved with AIDS are:

Antiviral Drugs Advisory Committee (code 12531);

Oncologic Drugs Advisory Committee (code 12542);

Vaccines and Related Biological Products Advisory Committee
(code 12388).

Also, the National Task Force on AIDS Drug Development (code
12602) announces its meetings on this system.


***** International Conference for People Living with HIV and
      AIDS, Cape Town, South Africa, March 6-10; Pre-
      Conference for Women, March 4 and 5

The Seventh International Conference for People Living with
HIV and AIDS, sponsored by the Global Network of People
Living with HIV and AIDS (GNP+), will be held in Cape Town,
South Africa, March 6-10, 1995. March 6 includes registration
and opening plenary, March 7 has a theme of health, March 8
of human rights and identities, March 9 skills building and
technical assistance, and March 10 is a business day for
GNP+.

For more information, contact the Conference Secretariat,
P.O. Box 27262, 8050, Rhine Road, Cape Town, South Africa,
phone [phone], fax [phone], email
[e-mail].

Note: On March 4 and 5, the ICW (International Community of
Women Living with HIV and AIDS) will hold a pre-conference
for HIV-positive women, in Cape Town. For information,
contact the conference secretariat in Cape Town, or contact
the London office of the ICW, phone [phone], fax 44-
171-222-1242.


***** Notice: Next Issue Delayed One Week

Our next issue, scheduled for publication on February 3, will
be delayed a week so that we can include coverage of the Jan.
29 - Feb. 2 Second National Conference on Human Retroviruses
and Related Infections, as well as the HIV Immune-Based
Therapies Workshop, and the CPCRA 16th Group Meeting. We will
return to our regular schedule with the February 17th issue.



***** AIDS TREATMENT NEWS
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AIDS TREATMENT NEWS reports on experimental and
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Treatment News does not recommend particular
therapies, but seeks to increase the options available.

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ISSN # 1052-4207

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