From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: ATN #163
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6482
Organization: unspecified
Date: Fri, 20 Nov 92 21:47:16 PST

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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 213/930-8820, fax 213/934-3919. 

** 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 410/837-2437. 

***** AIDS TREATMENT NEWS Published twice monthly 

Subscription and Editorial Office: 
   P. O. Box 411256 
   San Francisco, CA 94141 
   800/TREAT-1-2  toll-free U. S. and Canada 
   415/255-0588 regular office number 
   415/255-4659 fax 
Editor and Publisher: 
   John S. James 
Medical Reporters: 
   Jason Heyman 
   John S. James 
   Nancy Solomon 
Reader Services and Business: 
   David Keith 
   Thom Fontaine 
   Tadd Tobias 
   Rae Trewartha 

Statement of Purpose: 
AIDS TREATMENT NEWS reports on experimental and 
standard treatments, especially those available now.  We 
interview physicians, scientists, other health 
professionals, and persons with AIDS or HIV; we also 
collect information from meetings and conferences, 
medical journals, and computer databases.  Long-term 
survivors have usually tried many different treatments, 
and found combinations which work for them.  AIDS 
Treatment News does not recommend particular 
therapies, but seeks to increase the options available. 

Subscription Information:  Call 800/TREAT-1-2 
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   Please send U. S. funds:  personal check or bank draft, 
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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 
quotations are used. 

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Newsgroups: sci.med.aids