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J O H N   J A M E S  writes  on  A I D S
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Copyright 1992 by John S. James;
permission granted for non-commercial use.

AIDS TREATMENT NEWS Issue #163, November 20, 1992
   phone 800.TREAT-1-2, or 415/255-0588

CONTENTS:  [items are separated by "*****" for this display]

Call to Activists:  Focus Needed on Early Human Research
How to Advocate and Build Coalitions for Medical Research
   Funding
Protecting Body Composition in HIV Infection:  Interview
   with Nutritionist Cade Fields Newman
Announcements
   Berlin International Conference:  Dates and Deadlines
   SEARCH Alliance Seeks Medical Director
   Baltimore/Washington Area Clinical Trials Directory

***** Call to Activists:  Focus Needed on Early Human Research

by John S. James

     The main obstacle today to better AIDS treatments is early
in the drug-development pipeline.  Hundreds of potential
antivirals are coming out of laboratories and being published in
leading journals, but almost none of them move further, through
FDA-required animal toxicity tests and into early human trials.
Once a potential drug shows biological activity in humans (by
decreasing viral measures, or raising T-helper cells, etc.)  , it
would likely get enough attention to be developed appropriately.
But without such data, a drug is usually ignored, because:  (1)
the scientists who developed it cannot finance clinical research;
(2) pharmaceutical companies consider many factors other than
medical or scientific ones in deciding whether to develop an AIDS
drug; (3) the public has little consistent interest in a chemical
which has never been tested in humans; and (4) the Reagan-Bush
administrations did not take responsibility for managing the
research effort.  The resulting catch-22 -- no interest since
there is no data, no data since there is no interest -- has
blocked development of almost all potential AIDS drugs, and is
still blocking them today.

     With the new administration, this critical problem could be
fixed, allowing new treatments to come into use quickly if
appropriate.  As soon as there is evidence that a drug works very
well, it is likely to move exceedingly rapidly into wider use.
But if the same drug is never tested in people, or is only tested
for toxicity in HIV-negative volunteers, the necessary evidence
will not exist, and the drug will probably be delayed
indefinitely.

     The big danger now is inertia, because no force is yet
available to make the changes needed.  Pharmaceutical companies
are interested in short-term gain from drugs already on the
market or soon to be there.  Most influential AIDS researchers,
even when supported largely by federal grants and contracts, also
have business ties with these companies -- a situation which has
long distorted research policy and prevented potential new drugs
from being fairly considered.  The Washington, D. C., AIDS policy
organizations have not historically included research issues in
their "corporate culture," and might not be able to challenge the
research community when necessary; yet these organizations will
manage the articulation of the AIDS consensus which will go to
the Clinton transition team and administration.  Some candidates
now discussed as potential "AIDS czar" have avoided treatment
issues, apparently due to unwillingness to challenge their
scientific colleagues.  In short, all the conditions are in place
for a nightmare of business as usual, which could leave us, in
several years, about where we are today -- with no major new
antivirals and little advance in AIDS treatment except for
refinements in the use of AZT, ddI, and ddC.

     AIDS activists can make the difference, by never letting the
most critical issues in drug development be ignored.  So far,
however, early drug development is scarcely on the table among
activists.  It has been easier to focus on more immediate
concerns, such as conditions for expanded access, or equity in
access to clinical trials.  These issues are also important, but
without better drugs, they will not save many lives.

     The facts about excellent candidate drugs not getting into
the development pipeline, or not proceeding coherently to the
first tests of antiviral activity in humans, have been public
knowledge for years.  Yet this issue has received little
attention until now, because until this month there was no chance
of resolving it successfully.  Such a pervasive, systemic
malfunction cannot be repaired without national commitment and
high-level involvement and support.  The FDA could not solve the
problem by itself; neither could the NIH; neither could any
private organization.  The necessary national mobilization would
have required engagement and cooperation of higher Federal
officials, which was not available.

     Our biggest enemy today is the inertia of 11 years of
Federal AIDS mismanagement.  What can defeat it is an ongoing
determination to bring the most critical problems into the light
of public and professional attention, to keep them there as long
as necessary, and to insist that they be addressed.  AIDS
activists must take the lead in exposing the seriousness of
neglecting the flow of new drugs into early clinical development.

* * *

     Note:  The following is our submission to the National
Commission on AIDS, which is preparing recommendations for the
new president and Congress.  The Commission requested that these
statements, which were due November 23, include specific
recommendations to the executive and legislative branches.

Better AIDS Drugs:  The Biggest Obstacle

     To improve AIDS/HIV treatment and save lives of those
already infected, the greatest need by far is better
antiretroviral drugs.  And the main reason progress in new drugs
has been so disappointingly slow concerns obstacles near the
beginning of the drug "pipeline" -- in the late preclinical and
early clinical stages of drug development.  This part of the
development process has been overlooked, not because of
scientific disagreements but because of systemic political and
commercial snafus.  It urgently needs more attention:

     * Because of improvements by the FDA, the blockage near the
end of the drug pipeline has been greatly reduced; ddI, ddC, and
now d4T have been made available.  The problem is that no major
anti-HIV drugs are now in the pipeline, except for some, like tat
and protease inhibitors, which are still very early in clinical
trials.  Therefore, no important advances are likely from the
mainstream drug-development pipeline for at least several years.

     (An FDA press release dated October 19, 1992 said that the
FDA had "received" more than 500 IND applications "to test drugs
or biologics that may have potential in treating AIDS and other
HIV-related conditions."  But when the press release listed
"potential AIDS therapies publicly acknowledged by their sponsors
to be under study," it had to stretch considerably to include any
anti-HIV drugs.  The following is the FDA's list of "INDs for
experimental antiviral agents": compound Q, N-butyl DNJ,
ribavirin, ddC, beta interferon, d4T, and AZDU.  None of these is
likely to be a major advance in HIV treatment, and some appear to
be dead.  Vaccines, which can also be HIV treatments, are listed
separately; but there is considerable debate about whether any
therapeutic vaccine has shown clinical benefit or is ready for
large trials.  And as for the drugs the FDA could not name
because they had not been publicly acknowledged by their
sponsors, none could have progressed to large human trials
without being well known.  In short, no important HIV drugs will
emerge for some time.  The image of hope and competence projected
by the press release is an illusion.)

     * Dozens if not hundreds of potential anti-HIV drugs or lead
chemicals have been produced in university and other
laboratories, tested in viral cultures or in animals, and
published in major, peer-reviewed journals.  Usually development
stops there, since no one involved has the money to finish the
preclinical development required or to begin human tests.  Since
no public agency takes responsibility for shepherding these
compounds into further development if justified, they usually
wait indefinitely unless some pharmaceutical company picks them
up -- unlikely when there is no data on biological activity in
humans.

     * The existing AIDS trials networks (ACTG, CPCRA, CBCT) are
focused on a later stage of research.  Today they are often
conducting dubious trials because they have no compelling drugs
to study.

     * Some people believe that the National Cooperative Drug
Discovery Group program (NCDDG-HIV) is addressing this problem.
We have not attended their meetings, but we hear that they focus
on theories of rational drug design -- which clearly will be the
ultimate future of drug development, but so far has not been
effective for AIDS.  (Much of the focus is on improving high-tech
tools such as computer imaging systems, but the drugs produced
with those tools have not worked.)  For the current epidemic, we
also need empirical development of the most promising leads
available, even those resulting from chance discoveries instead
of high-tech science.  But this work is undervalued because it is
usually routine and not glamorous.

     * The bottom line is that we are suffering a serious
imbalance in research, because the drugs which most need
attention now for saving lives are not well positioned to build
the constituency needed to motivate their continued development.
Drugs which are already marketed, or almost ready for marketing,
can develop industrial, medical, and public constituencies.
Rational drug design generates both industrial and academic
support.  But no constituency champions a drug developed by one
scientist or academic team, with no pharmaceutical sponsor, and
with no human tests.

Recommendations

     * The executive branch must take responsibility for
proactively shepherding critical drugs through the development
process -- not just wait for some pharmaceutical company to move.

     * The U. S. National Cancer Institute has shown that
government can successfully carry out early human drug
development when necessary.  Both legislative and executive
branches should expand this work.

     * The executive branch should set up a medical research
ombuds office, where anyone who knows about research snafus of
any sort can report them, and can expect to get action when
appropriate.  Most of the problems which block clinical trials or
other research are red-tape accidents which could be cleared up
by a few phone calls from an office with the president's
authority behind it.  When broader policy issues are involved,
the office should research and prepare recommendations for the
executive branch, for Congress, and for foundations, companies,
and other private organizations.

***** How to Advocate and Build Coalitions for Medical
      Research Funding

by John S. James

     Note:  A treatment activist asked us for a memo which he
could provide to a meeting on the Clinton transition, and we
drafted the following in response.  Because we assumed a friendly
audience that did not need the humanitarian case restated, we
focused instead on fitting medical research into Clinton's
economic and political agenda.

     Because we could reasonably presume that AIDS will be
treated fairly, we discussed medical research overall, not AIDS
research in particular.  This way we could focus on a universal
appeal, since medical research is important to everyone.  And
this focus opens doors to coalitions with other health
constituencies.

     In the past, we were advised to soften or omit the problems
in medical research -- especially when Congress was considering
funding.  But now we have the prospect of a serious national
commitment to AIDS, as well as a major national policy shift from
military to civilian research.  As a result, the problems
themselves can be an integral part of research advocacy, since
they point the way to highly cost-effective management efforts.
Correcting key malfunctions which are preventing the translation
of research investment into clinical benefits can release
unimagined opportunities for achieving the results that count --
better practical treatments for people.

     One problem today is the belief in some circles that
medical-research progress is a root cause of medical cost
inflation, by producing better but ever more expensive treatments
-- essentially an argument that in medicine, ignorance is cost
effective.  A closer look shows that cost inflation reflects
mismanagement, not advancing knowledge.

*  *  *

     Biomedical research is politically unique because it is
personal in a way that other technologies are not.  Everyone
knows that they and their loved ones may (and probably will) face
life-threatening illness some day -- and that medical science
could make the difference between life and death, or between
recovery and lasting disability.  Medical research enhances the
security of everyone.

     Other technologies also save lives, but the public does not
see them the same way.  For example, a recent poll of Maryland
voters sponsored by Research!America found that 47 percent of
voters were willing to pay more taxes to increase medical
research -- several times the level of support for space or
national defense.

Biomedical research has other advantages:

     * If well managed it will reduce the cost of medical care.
Treatments which work well are usually less resource-intensive
than those which work poorly and require chronic care.  Medical
cost inflation stems from poor management, from incentives for
inappropriate use of technology, not from medical advance itself.
For example, in the Reagan-Bush administration, there was no
proactive leadership to assert the public interest -- and since
price competition in medicine is difficult to arrange within
ethical constraints, the commercial incentives were to research
and develop the most expensive (and therefore most profitable)
treatments, even when less expensive approaches could work as
well or better.

     * Medical research stimulates biotechnology, a major area of
U. S. strength and a key element of the future U. S. economy --
if we do not lose the lead to Japan, which has long been ahead in
certain areas, such as fermentation technology.

     On the other side, there is public impatience today with
cancer, Alzheimer's, and AIDS research particularly, because of
lack of productivity in delivering improved treatments and better
survival and care.  (Some medical fields, such as heart disease
and ulcer research, have delivered major benefits.) In AIDS,
where we have reported on research and treatment for six years,
it is clear that major management problems are inhibiting
progress, and that these can be fixed.  For example, the biggest
single block today to better AIDS treatments is the lack of a
workable system for getting the best of the hundreds of promising
drugs created in laboratories through preclinical and early
clinical development, to the point of the first test of
biological activity in 12 to 20 human volunteers.  If the drugs
could get to that point, it would be relatively easy to find
companies to take the successful ones the rest of the way.

     Other major, systemic problems in U. S. medical research
today include (1) the lack of viable career paths for
physician/researchers (who are often required to cash in their M.
D. chips due to accumulated debts before completing research
training), and (2) the lopsided influence of industry on
directing government research money, since almost everybody on
the committees which allocate public money has pharmaceutical
relationships on the side, resulting in grossly disproportionate
research emphasis on large-company drugs already marketed or
nearing the market, and no critical mass of advocates to champion
newer, emerging technologies.  (The latter problem may reflect not
so much the excessive power of pharmaceutical companies, but
rather the lack of countervailing assertion of the public
interest, due to ideological objections in the outgoing
administration.)  No one in government (or elsewhere) has had the
authority to attack these and other systemic problems.

     Much progress has been made in basic research, especially in
the development of tools and techniques which open doors to
progress against AIDS, cancer, and many other diseases.  But we
have not had the leadership to fix the obstacles blocking the
translation of basic knowledge into better treatments and cures.
With high-level attention, these obstacles can in large part be
overcome, allowing us to harvest the benefit not only of ongoing
basic research, but also of the great accumulated research
investment already made.

*****

Protecting Body Composition in HIV Infection:  Interview with
   Nutritionist Cade Fields Newman

by Dave Gilden

     The importance of malnutrition in AIDS progression is slowly
receiving more attention.  Specific micronutrient deficiencies
have been found with HIV that effect immune system function or
are related to brain and nervous system impairment.  [See AIDS
TREATMENT NEWS #134, September 6, 1991, "Zinc and B Vitamins in
HIV:  Overview and Interview," by Denny Smith; and AIDS TREATMENT
NEWS #158, September 4, 1992, "Nutrition at VIII International
Conference on AIDS," by Jason Heyman].  A broader issue is the
loss of the protein stores located in lean body mass as AIDS
progresses.

     Each individual seems to require a minimum store of protein
to support life.  There is an increasing awareness that death
among people with AIDS frequently occurs when that limit is
approached.  People with AIDS may be dying from a process similar
to starvation.  Many generalized symptoms of advanced AIDS,
including lack of energy and decreased ability to concentrate or
cope independently, could arise from tissue disintegration caused
by a loss of protein stores.

     The chronic, progressively debilitating aspects of AIDS and
HIV infection require treatment as much as do the acute, life-
threatening opportunistic infections.  The two are interrelated.
Ensuring proper nutrition is not just a matter of eating the
right foods.  It is a complex task requiring, among other things,
management of illnesses, mental attitude and drug interactions.
Sufficient physical exercise is also necessary to maintain or
recover body composition.

     We spoke with Cade Fields Newman, M. S., R. D., about the
multifaceted nature of nutritional support and its potential
benefits.  Ms. Newman is the founder of The Cutting Edge, a
nutritional consulting firm in Fremont, California that
specializes in advising patients with HIV.  Besides working with
individual doctors, she is currently organizing a nutritional
assessment service for the Physicians Association for AIDS Care
(PAAC).  It will supply member physicians with an evaluation of
the nutritional status of their patients and recommend ways to
control nutritional deficits and wasting.

*  *  *

     ATN:  How important would you say proper nutrition is?

     CFN:  Well, if I said I had a drug that would extend a
patient's life two or three years, that would improve their
quality of life, that would keep them in a situation where they
could provide their own care and keep them working, you would
think people would be flocking to it.  Yet, we do have that; it's
called "nutrition."  Although not a stand-alone therapy, it is a
very important part of overall treatment.  And in conjunction with
all the other things that are done, I believe that we can start
dealing with HIV as a chronic manageable disease, where a person
can live a normal, quality lifespan.

     ATN:  It seems obvious that the earlier one starts a
nutrition plan the better.  Once you become sick and lose
considerable amounts of weight, it will be hard to recover.  So,
where does one start?

     CFN:  Yes, prevention is absolutely key for a person to have
this vague thing called quality of life.  But nutrition is not
even a good stand-alone therapy to support nutritional stores.
What is required is a strong partnership between patient and
physician, hopefully with a multidisciplinary team's input.  The
patient has to be captain of a team.  For instance, I'm a
dietitian, but I cannot solve swallowing problems.  You may need
a speech therapist to evaluate that.  Or there might be a problem
with peripheral neuropathy and carrying out the tasks of daily
living.  Then, an occupational therapist should come in, or if
there are problems with range of motion or movement, a physical
therapist.  There should be a pharmacist to advise on the effects
of medications on nutrient utilization.  Also, there are the
nurses.  Patients see them more than anyone else, especially
home-care patients.

     All of us are simply advisers.  It's the patient's choice.
It is very important that they can assemble this team and that it
does what they want.  Otherwise people get advice on nutrition
from persons who do not have access to their medical records.
There is no way such persons can put together nutritional advice
that matches that person's individual medical profile.

     ATN:  But nutritional advice is not all that common at a
physician's office.  Most doctors don't have much nutritional
training.  How common is this ideal sort of team that you are
talking about?

     CFN:  It varies from place to place.  It occurs when you
have strong-minded, assertive patients who insist on it.  It's a
growing phenomenon.  A lot of us talked about team work for years
without doing anything about it, but now patients are insisting
on it.

     The doctor has to be in tune with what's happening.  If the
patient cannot maintain adequate nutritional stores, then medical
therapies will fail.  Drug therapies depend on your protein
stores, for instance on your serum albumin to carry that drug
where it needs to go.  Oral drugs depend on your ability to
absorb.  That, too, is based on nutritional status.  At least,
primary care physicians need to monitor overall treatments to
make sure that they do not conflict.  That cannot be done unless
people are working together as a team.

     ATN:  I want to talk about what this team will advise in
nutritional support.  But first can we briefly describe the
sources of inadequate nutritional balance in HIV infection and
AIDS?

     CFN:  There are three major reasons for malnutrition in HIV-
related disease.  The first is decreased intake.  That could be
because of anorexia -- just a lack of appetite -- which could
happen with depression or some of the drug interactions, a number
of different things.  The second part of this is malabsorption,
which happens quite often with HIV-related diseases in the
gastrointestinal track.  These two considered together would be
reasons for the body to starve.

     Besides this, the inflammatory response of the body to HIV
uses up protein stores in muscle tissue.  This creates a major
risk for malnutrition.  Also, the altered metabolism of nutrients
allows a person to hold onto and even generate fat stores while
maintaining or building lean tissue is difficult.

     Nutrient transport within the body may also undergo
alterations.  For instance, in a number of patients with advanced
disease, there are indications of an iron deficiency although
there may be other signs that there is plenty of iron.  It looks
like iron is not going where it needs to go, and just
supplementing with iron is not going to help.

     The picture is much more complex than not getting enough
food or malabsorption, and that's what makes nutritional
intervention so difficult.  Often we talk about this particular
chemical in the body doing that particular thing, but there may
be many different metabolic pathways that have to be set right.

     ATN:  OK, so let's start at the simplest level.  What are
the first steps an asymptomatic person with HIV should consider
for nutritional intervention?

     CFN:  Well, I know it's not hi-tech, but food is going to be
the best thing a person can do.  When we second-guess nutrition
and try to package it into little things to give people, we
sometimes get into trouble.  Food has many substances in it that
we don't know much about and that might be very important.

     If I were to prioritize what a person needs, the number one
priority would be fluids because without adequate hydration,
nothing works.  The second priority would be calories, because
without enough energy it doesn't matter what you are getting in
terms of protein.  It will not go where it needs to go.  The
third priority is protein, and the fourth priority is vitamins
and minerals, which cannot be used by the body without the first
three.

     ATN:  It's important to stress that problems with food
intake might be problems with energy -- not preparing food or
feeling energetic enough to eat.

     CFN:  Absolutely.  You need to figure out for each person
what they need, what they're getting, and strategies for getting
it.  And when they're having a bad day, they should have a stash
of food on board.  Many people do not have that, and when they go
through two or three bad days, they get behind.  At least if they
had a supply of food supplements, even instant breakfast, they
could get through better.

     Cooking can be very energy-draining; don't feel strange
about asking for help.  If someone wants to cook for you, let
them do it.  Nutrition covers quite a span.  Sometimes we get so
caught up in the biochemical changes in the liver, when a simple
chair in the kitchen or a better pair of eyeglasses would make
the biggest difference.

     For a person who is completely asymptomatic, a basic piece
of advice is to learn fundamental nutritional principles.  Learn
how nutrition interacts with immunity -- from a serious source,
not from some popular magazine.  Food safety -- proper storage,
cleaning and cooking -- is another very important skill to learn.
There are a number of opportunistic infections that could be
prevented if food safety were higher on people's lists.

     ATN:  Isn't there data that you should start collecting to
check on your nutritional status?

     CFN:  Yes, you should develop some individual strategies you
can put together to make sure you are getting what you need on a
day to day basis, but you should also develop a good contact that
will answer your questions and monitor your body composition
every six months.  Weight is not a good early indicator; its loss
shows that a lot of things have already happened.  It is very
important to get baseline data so you can know what the trends
are in mid-arm circumference and triceps skinfold [a measurement
of fat stores] and so forth.  These measurements reveal more than
weight alone does about the present state of body composition.

     You also need to monitor medical therapies.  Many people are
taking many medicines.  Drug interactions with the body, such as
nausea, vomiting, diarrhea, and toxicities to liver, kidney and
pancreas, can put you at risk nutritionally Another factor to
monitor is markers of nutritional status.  Albumin in the blood is
a good general indication of the state of the body's protein
stores, although infections can make this go down without any
relation to nutrition.

     ATN:  Are there specific nutrients that you would suggest
emphasizing in the diet?

     CFN:  I would concentrate on a nutrient-dense diet.  This
means that calorie per calorie you get a good amount of the other
things you need, like protein and vitamins and minerals.  Your
priorities are still fluids, calories and proteins, and then
micronutrients [vitamins, minerals, etc.].  Most people ask about
vitamins, but you need the first three to get any benefits at all
from the last one.  I would concentrate on fluid-containing,
calorie-containing and protein-containing foods and then make
sure I got adequate micronutrients.

     A group from the University of Miami in Florida did
recommend some very specific things in regard to supplementation
[M. K. Baum and others, "Interim Dietary Recommendations to
Maintain Adequate Blood Nutrient Levels in Early HIV-1
Infection," VIII International Conference on AIDS, Amsterdam,
July 19-24, 1992, abstract #PoB3675].  In early HIV infection,
increased intake of zinc and vitamins B2, B6, B12, A [or beta
carotene equivalent], C, and E, on the order of six to 25 times
the RDA [depending on the nutrient; more than six times for some
of them could be harmful.  See full report in M. K. Baum and
others, "Influence of HIV Infection on Vitamin Status and
Requirements," ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, volume
669, pages 166-174], was found necessary to maintain adequate
blood levels of these substances in some patients.  We don't know
yet how helpful normalizing these values is going to be.  This is
just an interim recommendation.  But we have seen people improve
cognitive function by normalizing B12 -- an important nutrient to
pay attention to if there is a decline in its level.  Similarly,
B6 seems to be important in protecting against neuropathy,
although an overdose of B6 also causes neuropathy.

     A generic recommendation would be just to eat adequate foods
and from there add a multivitamin maybe once or twice a day.  You
have to be careful about what you're taking.  Nutrients, like
drugs, can be very toxic, especially for people with HIV.  A
number of HIV-positive people may already have problems with
chronic hepatitis or other organ infections.  If you have liver
or kidney dysfunction or any pancreatic dysfunction -- maybe you
have been on ddI -- nutrients are not metabolized in the normal
way.  And a number of drugs are toxic to the liver.  This adds to
the potential compromise and toxicity when you take something
like vitamin A.

     ATN:  Do you favor other special dietary supplementation?

     CFN:  If a person cannot take in enough calories -- maybe
there's a problem with swallowing or someone just cannot fit in
the nutrients they need -- you can go to the calorie-packed
liquid supplements.  You can use those to augment nutrition,
preferably, and in some cases replace whole meals.  Stocking up on
these oral supplements is another way of preparing for bad days.

     A different kind of supplementation is exercise.  Regular
exercise is highly beneficial.  Also, if you want or need to gain
weight, then you need to do so along with exercise because
padding yourself with fat is not particularly helpful.  If an
opportunistic infection occurs, you need protein stores to resist
it and make your drug therapies work.

     There is a high correlation between muscle mass and clinical
well-being.  Protein makes the body function; immunity is based
on protein stores, too.  And exercise promotes protein formation
in tissues throughout the body.  Here, resistance exercise, like
body building, is more important than aerobic exercise.

     Another strategy that promotes protein-building is regular,
frequent meals.  One study found that people who eat at least
four times a day, including a snack an hour or so before
sleeping, did better in terms of nitrogen balance than anyone who
ate less than four times a day.  Fortifying protein stores should
be a central preparation for coping with AIDS.

     ATN:  When severe immune deficiency does come about, what
are the issues then?

     CFN:  Most people who lose weight in conjunction with an
opportunistic infection have a hard time gaining it back, if they
ever do.  And when they do gain it back, they may not gain back
the protein stores they need, just fat and fluids.  This is the
central problem.

     ATN:  Aren't there ways to recover?

     CFN:  Yes, there are four strategies for regaining lean body
mass, and nutritional support is only one of them.  The first
defense is prompt and effective treatment for opportunistic
infections when prophylaxis fails.  We can prevent much
malnutrition by stopping the cascade of events surrounding
opportunistic infections.

     The second line of the defense is hormonal modulation and
anti-inflammatory therapies.  Some patients have low testosterone
levels, for example.  By replacing that, you can maintain or
increase lean body mass because that's one of the effects of
testosterone.

     Elevated cytokines, such as some interleukins, have been
proposed as causing the wasting effect.  I'm not so sure that
anti-cytokines will prove to be a good therapy by themselves, but
perhaps they will be helpful in conjunction with other
treatments.

     Anti-inflammatory agents abound.  You have to be careful to
block the harmful aspects of inflammation, those that drain
protein stores for energy, and not the beneficial ones.  Simple
aspirin and fish oil reduce the level of inflammatory
prostaglandins to give the body an opportunity to recover lean
tissue.  Fish oil may be more effective earlier rather than
later, though.

     ATN:  You mentioned how important exercise is early stages
of disease, but does it have an effect later on, when movement is
harder?

     CFN:  Yes, exercise is the third defense strategy.  It is
still important in protecting body composition or gaining back
lean body mass after you have lost weight.  It's tough when you
are experiencing a lot of fatigue or physical limitations, but
there are people who can put together exercise programs even for
those who are in wheelchairs.

     ATN:  And nutritional support is the fourth strategy?

     CFN:  Finally, we come to ensuring an adequate diet.  In
AIDS, a host of opportunistic infections affect eating.  We
mentioned aspirin before; that and other anti-inflammatories are
also used for pain management.  Pain management is an issue that
is not fully addressed for many people with AIDS, and it can be
key, not only for overall quality of life, but also for the
ability to eat.

     Just about everybody with AIDS will have diarrhea at some
point, despite attention to food safety.  Treating the underlying
cause of diarrhea, if possible, is the most effective course of
action.  Also, anti-diarrhea drugs may be combined with
nutritional strategies.  Fasting during episodes of diarrhea is
not recommended.  Emphasizing sources of soluble fibers (such as
bananas, oatmeal, applesauce and potatoes) while removing sources
of crude fiber and maintaining an overall balanced diet is more
appropriate.  Replacing lost fluid and electrolytes, especially
potassium and sodium, is crucial.

     ATN:  Rehydration and electrolyte replacement can take place
intravenously as well as through the diet.  Eventually, simple
dietary techniques may not be enough to provide sufficient
nutrition.  Liquid food supplements can be added when someone
cannot or does not take in enough food for whatever reason.
Feeding through a tube to the stomach also has its place in
people physically unable to eat.  But in the extreme case, there
is parenteral feeding (through a catheter attached to a vein),
which avoids the GI tract entirely.  What role does it play?

     CFN:  Partial or total parenteral nutrition can help people
get over the hump when disease causes extreme malabsorption.  It
is necessary to start early, though.  Don't let people not eat
for three to fourteen days before introducing parenteral
nutrition.

     Parenteral nutrition does not have to be permanent.  People
feel that if they go on TPN [total parenteral nutrition], they're
stuck with it forever.  That is not true.  In certain diagnoses,
such as CMV colitis, people may be maintained on TPN throughout
their lifetime.  Even then, they can modify oral intake and in
some cases reduce their dependency on TPN.

     The second point I would like to make is that aggressive
support does not equal TPN.  You can be aggressive with peas and
carrots and palliative with TPN.  To find out what the appropriate
support is, the patient can be clinically profiled into
diagnostic sub-groupings.  For instance, if the person is
experiencing some depression and is adequately absorbing
nutrients, they may simply need to focus on "maximizing food
intake," by eating nutrient-dense foods.

     ATN:  What about using Megace [synthetic progesterone] or
Marinol [synthetic THC, the active ingredient in marijuana] to
stimulate appetite?

     CFN:  Marinol seems to work well for nausea, and some
patients prefer it for increasing appetite.  Some people complain
about feeling drugged out, though.  Some say that smoking
marijuana works better.  It's quicker, and avoids their queasy
stomach.  But the smoke can present a problem, especially for
those with respiratory infections.

     Patients on Megace tend to gain fat, according to studies
using therapeutic doses of 800 mg/day.  Many people use a lot
less than that.  It has been speculated that a slow weight gain
associated with lower than established therapeutic doses may
include more lean body mass.  When used with people who have a
mechanical or pain reason not to eat (rather than reduced
appetite), Megace may be detrimental through increasing the
desire and not the ability to eat.

     In advanced HIV infection, you may have "futile cycling" of
fat going on, where fat stores are broken down in the liver and
then rebuilt by the liver.  This wasteful process results in
consumption of body protein for energy.  If you throw
rehabilitative levels of calories at someone in this state, you
may just get more fat and not the protein stores that are needed.

     ATN:  Appetite is closely tied to mental outlook.  And
mental outlook can be impaired by not eating.  This brings up the
relation of mental health support to nutritional therapies.

     CFN:  Help in avoiding depression or handling stress becomes
more and more necessary as HIV infection progresses.  It is key
to motivating HIV-positive people to follow other therapies.
Again, nutritional support, like medical support, will not be
most effective all by itself, as a stand-alone therapy.

     ATN:  Also, speaking of specific substances like Megace or
Marinol, I notice we haven't spoken much about specific vitamins
and minerals later on in the disease.

     CFN:  The significance of vitamin and mineral deficiencies
are not well established.  Other micronutrients that we look at
besides the ones mentioned before in connection with the
University of Miami group include selenium and folate.  One
doctor I know has had good results improving patients' quality of
life with magnesium supplements.  But micronutrient deficiencies
seem to be geographically dependent.  Some of this has to do with
the minerals in the local soil.  A major factor is the variation
from place to place in the way physicians treat AIDS.  Drug
interactions have a large influence on micronutrient absorption
and utilization.  For example, pyrimethamine and trimetrexate,
which are used in treating toxoplasmosis and pneumocystis,
interfere with folate metabolism.

     ATN:  So, when taking vitamins and minerals, you have to
understand the roots of the deficiencies?

     CFN:  Oh yes.  Blood indications of low iron may not be
resolved by iron supplementation if it is really a cellular level
nutrient transport problem due to low protein stores.

     You need to see what is best for the patient.  If
micronutrient levels normalize, is that valuable, or are other
things going on that are still disruptive?  Again, addressing
problems that may cause alterations in nutritional, and
specifically micronutrient, status may be most effective.

     ATN:  Where patients find reliable information about
nutrition, and learn more about the full potential for dietary
changes to modify disease progression?

     CFN:  Patient information is available through a number
sources.  To get a listing of educational pieces designed for HIV
patients you can contact the National AIDS Information
Clearinghouse at 1-800-458-5231.

     To find dietitian services for evaluation and counseling,
request a referral from your physician.  The next step is to
locate a dietitian who has training and experience in HIV-
related nutritional issues.

     Also, contact major city public health departments and ask
for phone numbers of AIDS nutritional networks.  In the New York
area, you can contact Nutritionists in AIDS Care at 212-439-
8073.  Arizona, California and other states have networks as
well.  Several AIDS support agencies have added dietitians to
their staffs, including the San Francisco AIDS Foundation, and
Bronx AIDS Services.  Local home meal delivery services can also
be a place to start.

     [Note:  To contact HIV nutrition specialists at The Cutting
Edge, the organization founded by Cade Fields Newman, call 510-
797-9768.]

***** Announcements:

** Berlin International Conference:  Dates and Deadlines

     The major international AIDS conference of 1993 will be the
IXth International Conference on AIDS, Berlin, June 7-11, in
affiliation with the IVth STD World Congress.  Abstracts, on an
original copy of the form provided by the conference and with
five photocopies, must be received no later than January 15,
1993.

     Advance registration before January 31 is at a reduced rate,
DM 800 regular and DM 250 student.  After January 31 and on site,
registration is DM 950 regular and DM 350 student.

     The conference phone number is 49-30-857903-0; fax is 49-30-
857903-27.

** SEARCH Alliance Seeks Medical Director

     SEARCH Alliance is seeking a medical director to develop and
manage community-based clinical trials in Los Angeles.  Candidate
should be an M. D. with strong clinical skills, HIV/AIDS clinical
trials experience, and knowledge of research methodology.  Send
curriculum vitae to:  Board of Directors -- Medical Committee,
SEARCH Alliance, 7461 Beverly Boulevard, Suite 304, Los Angeles,
CA 90036, phone [phone], fax [phone].

** Baltimore/Washington Area Clinical Trials Directory

     A directory of more than 50 AIDS/HIV clinical trials
recruiting volunteers in the Baltimore and Washington areas has
been published by AIDS Action Baltimore.  The directory includes
trials at Johns Hopkins University, the University of Maryland,
Georgetown University, the National Institutes of Health, Walter
Reed Army Institute of Research, Whitman-Walker Clinic, Chase-
Brexton Clinic, and other locations, including community-based
trials through physicians' offices.  Vaccine trials (for HIV-
positive volunteers), pediatric studies, and expanded-access
programs are listed.

     The 36-page directory includes a trials index, a glossary,
and notes on other relevant publications and resources.

     For a copy of The Directory of Clinical Research in AIDS for
Baltimore & Washington, September 1992, contact AIDS Action
Baltimore, 2105 North Charles St., Baltimore, Maryland, 21218,
phone [phone].

***** AIDS TREATMENT NEWS Published twice monthly

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Editor and Publisher:
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   John S. James
   Nancy Solomon
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AIDS TREATMENT NEWS reports on experimental and
standard treatments, especially those available now.  We
interview physicians, scientists, other health
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survivors have usually tried many different treatments,
and found combinations which work for them.  AIDS
Treatment News does not recommend particular
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ISSN # 1052-4207

Copyright 1992 by John S. James.  Permission granted for
noncommercial reproduction, provided that our address
and phone number are included if more than short
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