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AIDS TREATMENT NEWS Issue #204, August 5, 1994
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

HIV RNA: New Blood Test for Individualized Therapy and Faster
Trials

Nutrition and AIDS: Interview with Kristin Weaver, Bay Area
Nutrition Counseling Center and Clinic (BANC), at San
Francisco General Hospital

California: MediCal Cut in Monthly Prescription Allowances
Starting October 1

Announcements, Notes

   Kaposi's Sarcoma -- Major Overview Published

   Interim AIDS Coordinator Announced

   Medical Marijuana: 89 Percent Support

   Correction -- Zerit (d4T) Information Number



***** HIV RNA: New Blood Test for Individualized Therapy and
      Faster Trials

by John S. James

During the last two years, new blood tests for HIV viral load
have increasingly been used in clinical trials and other
scientific research. There is great interest among
researchers, as the early, preliminary results of major
studies are showing that changes in viral load due to change
in therapy can predict clinical benefit in patients.
Meanwhile, the tests are about to come into use (outside of
formal studies) in medical practice for individualizing
patient care; the challenge will be learning when to use them
and how to interpret the results. But it is widely agreed
that a reliable blood test for viral activity in the body --
if it can help predict which drugs will be successful for a
particular patient, as these tests do seem to do -- could
revolutionize HIV medicine by improving treatment with
existing drugs, as well as shortening the time required for
new treatments to be proven.

We believe that this development is more important than most
physicians, treatment activists, or even the scientists
working with the tests may realize, for the following
reasons:

* Existing treatments do seem to work well at certain times
for many people. A scientifically validated way to guide each
patient to the best treatment for him or her could
substantially improve patient care now, without the need to
wait for better drugs to become available.

* A reliable viral test would enable antiviral drugs -- and
even some immune-based and other kinds of therapies to be
tested much more rapidly and less expensively than under the
current system. This should greatly shorten the time required
to make better treatments available.

Now it usually takes years, and hundreds (if not thousands)
of patients to show that an AIDS treatment improves survival,
or reduces the number of opportunistic infections. In
contrast, blood tests often show clear results in weeks, and
relatively few patients may be enough to produce statistical
proof. But first, it must be shown that a decrease in viral
load caused by a change in drug therapy indicates a real
benefit for the patient.

* "Alternative" treatments -- those without a rich, well-
connected institution behind them -- could also be tested
scientifically, perhaps in small, community-based studies.
Those which are worthless can be discarded, and those which
are found to be effective can be targeted to the particular
patients most likely to benefit.

* Similarly, traditional medicines being used around the
world in HIV treatment could be screened with these tests,
potentially making effective treatment available for the
first time for millions of people who cannot obtain high-
priced pharmaceuticals. At the same time, validating
traditional remedies may provide new options to improve
treatment for those who already have access to conventional
medical care.

* We believe that the biggest obstacle to AIDS treatment
development, the major reason it has not been productive, is
that the combination of high regulatory hurdles and lack of
national will has made it impossible for low-priority
treatment ideas, those with only a few champions and little
or no industry or government support, to begin to be tested
so that they can build credibility if they work. Since most
major medical advances start as low-priority ideas, and prove
themselves through a series of surprises, the current system
-- which limits the field to projects which already have
major support -- chokes off the wellspring of innovation,
virtually guaranteeing stagnation. This problem does not
correct itself, due to peoples' natural tendency to focus on
what they already consider important, instead of cultivating
development paths for ideas which are currently outside of
their understanding and therefore may not appear attractive.
Giving the power to determine what works to individual
patients and physicians can allow new ideas to proceed,
breaking the existing monopoly on drug development and the
resulting choke hold on our future.

All these benefits depend, of course, on whether what is
being measured by the new tests is a useful indicator of how
well a treatment is working. It would seem logical that
lowering the amount of HIV in the blood would be an
improvement. But experts are cautious, because prior viral
tests (especially the p24 antigen test) have been too
inaccurate to be very useful in drug development. Much
remains to be learned; but the information now available is
encouraging.

Background: What Is HIV RNA?

The genetic information for almost all living things is
stored in the nucleus of cells, in a chemical called DNA. In
the body, the same information in DNA can be transcribed into
RNA; then the information in the RNA is translated into
proteins, which determine the structure and function of the
cell.

Retroviruses (such as HIV), however, have their genetic
information in RNA. When the virus gets inside a cell, the
information is transcribed in reverse into DNA, which then
becomes part of the cell's genetic inheritance. The cell can
then produce new viruses, or be damaged in various other
ways, sometimes producing abnormal cytokines which can cause
illness.

Each individual HIV virus has two copies of the RNA which
specifies its genetic information. The new tests for viral
load detect this RNA, and the test results are usually given
as number of copies per milliliter of blood plasma. For
example, if someone get a test result of 100,000 (a fairly
high number), it means they have 100,000 copies of the RNA
(or 50,000 virus particles) per milliliter of plasma.

What a Blood Test Needs to Do to Be Useful

First, of course, any test used in research or in clinical
care must be accurate and reliable. Quality assurance is
necessary; it can be done by sending known samples to the
labs that run the test. The samples are coded so that the
labs do not know what is in each; their answers are then
compared against the correct values.

But also, to be useful for drug development or for
individualizing patient care, a test must be validated --
that is, we need to know that what the test measures has
clinical usefulness. Different tests are useful for different
purposes.

For example, the T-helper count (CD4 count) clearly is useful
for prognosis -- predicting how an individual patient is
likely to do. For example, pneumocystis almost always occurs
when the T-helper count is under 200 or 250, and CMV
retinitis when the count is under 50. (These numbers are for
adults; the numbers for young children are entirely
different.) But while the T-helper count clearly provides
predictive information, this does not automatically mean that
a change in T-helper count caused by a drug will indicate a
corresponding change in the prognosis of patients. In fact,
the well-known Concorde study of early use of AZT found that
those taking the drug had higher average T-helper counts than
those who did not, and this difference persisted for the
three years of the study; however, for reasons not well
understood, it did not make much difference in death rates or
other clinical outcomes -- casting doubt on the use of the T-
helper count as an early signal of whether a treatment is
working.

In analyzing a clinical trial where some patients are
randomly assigned to one treatment regimen and some to
another, it is easy to tell if one treatment raises the T-
helper count (or other blood-test result) more than the
other. Also, it is statistically straightforward to determine
if one treatment group does better than the other. But it
takes more complex statistics to tell that the blood test is
actually showing that the drug is working -- to rule out the
possibility that the drug helps the patient, and also just
happens to change the blood test independently. In the latter
case, the test could be worthless for indicating in advance
whether another drug is also going to work.

This means that a trial with clinical endpoints (which may
take several years to generate enough deaths or serious
illnesses to produce statistical proof that one treatment is
better than the other) may be necessary to validate a new
blood test. Fortunately, the tests for HIV RNA can be run
with frozen blood samples, which have already been saved from
past trials, where the outcome for each patient has already
been recorded. This retrospective validation is now well
underway, and preliminary results from three major trials,
presented by different groups at a recent scientific meeting,
have suggested that changes in HIV RNA do indeed predict
changes in clinical outcome cause by drug treatment. These
results are preliminary, and questions remain.

[Note: An alternative strategy would be to not wait for the
validation step, by making the reasonable presumption that,
other things being equal, a low viral load in patients is
better than a high viral load. Then a drug which reduced
viral load could be considered effective for purposes of
approval, unless there was other information which rebutted
the presumption; safety, of course, would have to be proven
separately, but proof of efficacy, not safety, is the
bottleneck in drug development. The benefit of this approach
is that small companies would have a chance to develop and
market AIDS treatments; and large companies would have the
ability and incentive to develop their drugs rapidly. We
believe that this strategy would serve the public better than
current approaches for discovering and developing better AIDS
treatments; but for various reasons it would be difficult to
sell politically.

What we do unquestionably need is better information on how
to use and interpret these tests. There is a danger that
future studies will focus too much on definitive academic
proof that the tests can be useful -- which we are learning
anyway. Instead, they should focus on getting practical
information for physicians who are caring for patients.]

Testing for HIV RNA -- Two Different Technologies

Two completely different methods, quantitative PCR (currently
being developed as a standardized test kit by Roche Molecular
Systems, Somerville, New Jersey) and branched DNA (developed
by Chiron Corporation, Emeryville, California), are now being
widely used in research to test for the amount of HIV RNA in
blood. A short explanation of how they work appeared in
"Better Tests for HIV Activity; Interview with Mark B.
Feinberg, M.D., Ph.D., AIDS Treatment News # 186, November 5,
1993. These two different kinds of tests measure the same
thing, and usually they give comparable results.

But each kind of test has different strengths and weaknesses.
At present, the branched DNA test has a cut-off at 10,000
copies of HIV RNA per milliliter; it cannot measure values
lower than that. (Soon the cutoff will be reduced to 5,000
copies per milliliter.) The quantitative PCR testing service
which is now commercially available through reference
laboratories can go down to 200 copies per milliliter. No one
yet knows if keeping the counts under 5,000 is good enough
for maintaining health; if not, some patients will need to
use PCR to track lower counts.

On the other hand, the branched DNA test appears to be more
consistent than quantitative PCR in measuring different
subtypes of HIV (although Roche points out that what matters
is change in time within each patient, so this might not be
an issue). Which test is more accurate is in dispute.
Branched DNA is much easier than PCR to run in the
laboratory, which should help to make it more accepted in
widespread use.

Eventually one of these testing technologies may prove better
overall than the other. But at this time, researchers using
the tests in clinical trials are about equally interested in
both.

Regulatory Issues

Anyone using HIV RNA tests now, before they are part of
standard medical practice, should understand that, because of
how medical tests are regulated, both quantitative PCR and
branched DNA tests are becoming available to physicians and
patients in a test format that does not require FDA approval.
Therefore, the customer must be extra careful about getting a
good-quality test.

In the U.S., medical tests are traditionally regulated in two
different ways. Usually, the test is provided in the form of
a standardized kit, which contains all the materials and
instructions required so that any qualified laboratory can
test samples. The FDA must approve such a kit before it can
be widely used in the U.S. -- and therefore it takes longer
for the standardized test kit to become available for medical
practice.

But a company can also set up its own sophisticated
laboratory, sometimes called a reference laboratory, which
can perform the testing service. To offer this service
without a kit is much more difficult than running a kit
produced by somebody else, since the lab has to buy or make
all of the materials itself, check their purity, etc. In this
case, the company can offer the test commercially as a
service, not a product, and this testing service is not
regulated by the FDA. Because FDA approval can take some
time, the availability of the standardized kit can be a year
or more behind the availability of the same test through a
testing service by a reference laboratory.

During this time before FDA approval, how can one be
confident that the test is accurate? We suggest purchasing
the test through the companies which are experts in this area
-- Roche Biomedical Laboratories for quantitative PCR, and
Chiron Corporation for branched DNA. Other companies can run
these tests through various agreements with the patent
holder, setting up their own reference laboratories; but then
the patent holder does not run these laboratories and cannot
guarantee their quality. Both Roche and Chiron have immense
investments in their technologies (which not only can test
for HIV, but will also have many other uses in medicine); and
both know the technologies at least as well as anyone else.
They have the incentive and also the means to make sure to
have good quality control before offering their tests to
physicians. Also, government and other researchers have done
considerable work with their tests and would quickly notice
any serious problem. These protections are not available if
one selects a "brand X" HIV RNA test.

And later, even after the FDA-approved kits become available,
there will still be concern that the laboratory personnel who
run the tests be properly trained, to avoid significant
variation due to lack of quality control.

The Challenge: Interpreting Test Results

When one has one's blood tested for HIV RNA, the result comes
back as a number of copies of viral RNA per milliliter; this
number can range from a low of 200 to a high of over a
million. Sometimes the result will be that the number of
copies was below the cut-off for the test -- 200 copies for
PCR, 10,000 copies (soon to be 5,000) for branched DNA. A
single number is hard to interpret; it is more important to
watch how the number changes over time.

HIV RNA is a very sensitive measure, and can change
considerably in response to many things. Some persons with
HIV can have as much as a three-fold variation in the number
from day to day, for no known cause; others have less
variability. Immune stimulation -- for example, from a flu
shot -- can cause a large temporary increase. Because of this
variability, a small change -- even a two-fold or three-fold
change -- in a single number might not be meaningful.

AZT and other approved AIDS treatments often cause a drop of
about one log (ten fold) in HIV RNA level; however, this drop
is usually not sustained, probably because the virus develop
resistance to the drugs. Saquinavir, the experimental
Hoffmann-La Roche proteinase (protease) inhibitor, did about
the same -- close to a one-log drop, but not sustained.

Many researchers believe that, to be a major advance in AIDS
treatment, a new drug, combination, or other treatment
regimen should produce at least a two-log (100 fold) drop in
HIV RNA levels, and that this drop must be sustained -- for
many months, hopefully for years. The experimental protease
inhibitor now being tested by Merck & Co. has produced a two-
log or greater drop in a few patients, but again the decrease
was not sustained; within a few months, the HIV RNA levels
went back up. (For a look at indications of clinical benefit
from even the temporary drop, see "Antivirals and Immune
Recovery: Interview with Michael S. Saag, M.D., AIDS
Treatment News #200, June 3, 1994.)

Since an ideal treatment will be hard to find, we will have
to settle for less at first. Perhaps several treatments which
each alone have a smaller effect could be combined to give
better results. As HIV RNA tests come into wider use,
physicians and patients will be trying all kinds of treatment
regimens while watching the viral load. This could lead to
important advances in the search for better treatments or
cures.

Still there are questions. The HIV RNA test only tells how
much virus is in the blood; it does not tell how pathogenic
that virus is. Also, the blood level of the virus might or
might not be a good indicator of what is going on elsewhere
in the body. Much remains to be learned; but meanwhile, it
does seem reasonable to use the level of HIV RNA in the blood
to help guide treatment decisions, with the goal of lowering
the viral load and keeping it low.

The Future

The quantitative PCR test for HIV RNA is now available to
physicians; in fact, it has been available since late 1993,
although this has not been widely known. Chiron has announced
that its branched DNA test will be available to physicians
starting August 15.

A major scientific meeting on these issues -- Surrogate
Markers of HIV: Strategies and Issues for Selection and Use
-- will be held October 12-14 near Washington D.C.; it is
being organized by Cambridge Healthtech Institute, Waltham,
Massachusetts. It's conclusions may soon become obsolete,
however, as important new data from ongoing trials will
become available in the months after the meeting. These new
trials, prospectively designed to include testing for HIV RNA
(as compared to previously-run trials which fortunately
happened to have some frozen blood in storage) are important
for various reasons. For example, the old trials did not
process the blood properly for the new HIV RNA tests; the
tests can still be run, but some of their sensitivity is
lost. HIV RNA testing may work even better in ongoing trials,
where this is not a problem.

A major future regulatory issue is whether HIV RNA will have
to be re-validated for each new class of drugs -- requiring a
large, long-lasting trial with "clinical endpoints" (death or
major opportunistic infections) before the viral load tests
would be accepted as proving efficacy of the new  drug class.
[For example, if the viral load as measured by HIV RNA is
shown to predict patient benefit from nucleoside analog
treatments (AZT, ddI, etc.), can it then be used similarly
for protease inhibitors, or will another major trial be
required to validate it for protease inhibitors first?] If
the FDA decides that the answer is yes -- and it may be
leaning that way at this time -- then the result could be to
add years to the development time of every new class of
drugs, and create a multimillion dollar disincentive to the
development of new kinds of AIDS treatment.

How to Order HIV RNA Tests

* Quantitative PCR for HIV RNA: Physicians can order this
test through Roche Biomedical Laboratories, Research Triangle
Park, North Carolina; the customer service number is 800/533-
0567, 8 a.m. - 6 p.m. Monday through Friday, 8 a.m. - noon
Saturday, Eastern time.

* Branched DNA for HIV RNA: Chiron Corporation will offer
this test to the HIV clinician starting August 15, 1994.
Sample collection, shipping, and other client services will
be handled by Nichols Institute, a commercial laboratory
which can serve clients throughout the U.S. Information about
this test can be obtained by calling 800/553-5445.

Bibliography

Note: Recent preliminary information on the validation of HIV
RNA (as an indicator of benefit of drug therapy) is not yet
public, so it is not described in the references below.

Bagnarelli P, Valenza A, Menzo S, and others. Dynamics of
molecular parameters of human immunodeficiency virus type 1
activity in vivo. Journal of Virology. April 1994; pages
2495-2502.

Dailey P, Lindquist C, Collins M, and others. Detection and
quantitation of HIV RNA from lymph node tissue using a
branched DNA (bDNA) signal amplification assay (Chiron
Quantiplex* HIV-RNA assay). The First National Conference on
Human Retroviruses and Related Infections, December 12-16,
1993, Washington, DC [abstract #313].

Detmer J, Collins M, Zayati C, Irvine B, Kolberg J, and Urdea
M. Comparative quantification of gold standard HIV-RNA
representing subtypes A-E using the Quantiplex* HIV-RNA
assay. The First National Conference on Human Retroviruses
and Related Infections, December 12-16, 1993, Washington,
D.C. [poster #204].

Gupta P, Kokka R, Neuwald P, Kern D, Rinaldo C, and Mellors
J. Expression of HIV-1 RNA in plasma correlates with the
development of AIDS: A Multicenter AIDS Cohort Study (MACS).
Ninth International Conference on AIDS, June 7-11, 1993,
Berlin [abstract #2481]

Holodniy M, Eastman PS, Mole L, and others. Reduction of
plasma HIV viral load during ddI/ZDV combination therapy in
the presence of ZDV resistance. The First National Conference
on Human Retroviruses and Related Infections, December 12-16,
1993, Washington, D.C. [abstract #9].

Holodniy M, Mole L, Winters M, and Merigan TC. Diurnal and
short-term stability of HIV virus load as measured by gene
amplification. Journal of Acquired Immune Deficiency
Syndromes. April 1994; volume 7, pages 363-368.

Mellors J, Kingsley L, Gupta P, and others. Detection of
plasma HIV RNA by branched DNA (bDNA) signal amplification
predicts early onset of AIDS after seroconversion. The First
National Conference on Human Retroviruses and Related
Infections, December 12-16, 1993, Washington, D.C. [abstract
#274].

Mulder J, McKinney N, Christopherson C, Sninsky J, Greenfield
L, and Kwok S. Rapid and simple PCR assay for quantitation of
human immunodeficiency virus type 1 RNA in plasma:
Application to acute retroviral infection. Journal of
Clinical Microbiology. February 1994; pages 292-300.

Pachl C, Saxer M, Elbeik T, and others. Quantitation of HIV-1
RNA in plasma using a branched DNA (bDNA) signal
amplification assay: Evaluation of specimen collection and
stability. The First National Conference on Human
Retroviruses and Related Infections, December 12-16, 1993,
Washington, D.C. [abstract #312].

Pachl C, Elbeik T, Saxer M, and others. Quantitation of HIV-1
RNA in plasma using a signal amplification branched (bDNA)
assay. 93rd General ASM (American Society for Microbiology)
Meeting, May 16-20, 1993, Atlanta, GA.

Saksela K, Stevens C, Rubinstein P, and Baltimore D. Human
immunodeficiency virus type 1 mRNA expression in peripheral
blood cells predicts disease progression independently of the
numbers of CD4+ lymphocytes. Proceedings of the National
Academy of Sciences, USA. February 1994; volume 91, pages
1104-1108.

Sninsky JJ and Kwok S. The application of quantitative
polymerase chain reaction to therapeutic monitoring. AIDS.
1993; volume 7 (supplement 2), pages 529-534.



***** Nutrition and AIDS: Interview with Kristin Weaver, Bay
      Area Nutrition Counseling Center and Clinic (BANC), at
      San Francisco General Hospital

by Tadd Tobias and John S. James

Kristin Weaver, R.N., M.S.N., C.N.S.N., is the Clinical
Research Coordinator and Nursing Director of GI
(Gastrointestinal) Nutrition Services at San Francisco
General Hospital. We spoke with her recently about the
relationship between HIV disease and nutrition. This is part
I of the interview.

Note: Recently San Francisco General Hospital was rated best
in the U.S. for AIDS care, for the fifth year in a row, in a
poll of medical professionals conducted by U.S. News and
World Report, (published in the July 18, 1994, issue).

ATN: You work with both inpatients and outpatients who live
with HIV disease. Can you tell us about the GI Services at
San Francisco General Hospital and the Bay Area Nutrition
Clinic.

KW: When I became the Clinical Research Coordinator here at
SFGH, the physicians here were doing a lot of procedures for
patients with dysphasia, diarrhea and other GI-related
symptoms. We did an in-patient chart audit and found
approximately 70% of patients had a diet inappropriate for
the symptoms they were experiencing. In addition, nutrition
was often at the bottom of the list when it came to providing
care.

We formed a multi-disciplinary team under the auspices of the
Division of Gastroenterology, Hepatology, and Clinical
Nutrition. The team consists of a GI specialist,
pharmacologist, dietitian, and nurse, who work one-on-one
with hospitalized patients, to address the specific problems
interfering with optimal nutrient intake. But when patients
were discharged home, there would be no outpatient followup.
It was difficult to have much of an impact in the short time
that people were hospitalized; we wanted to expand our work
to reach outpatients earlier. That's why we started BANC,
which also is a multidisciplinary approach to assessing and
addressing the nutritional concerns of people with HIV. In
this outpatient clinic, we help to keep people from losing
more weight, or help to keep people nutritionally sound and
prevent the onset of weight loss. Patients are active
participants in their own care at BANC.

It's important to reach people early. It is well-documented
that during World War II children who were malnourished
developed pneumocystis. If you are malnourished, the immune
system suffers. If you are sick, your nutritional needs go up
overall. Currently 50-60% of all hospital patients are
malnourished. Malnutrition leads to increased length of
hospitalization due to repeated complications requiring
treatment. If almost all HIV-infected people eventually
develop malnutrition, one might speculate that malnutrition
is a cofactor in increasing health-care costs.

ATN: How do you know if people are malnourished? It's subtler
than our typical image of an emaciated individual.

KW: That's a very good point. One person was admitted to the
hospital with cryptococcal meningitis. He looked pretty well
buffed -- not like he had missed many meals. But when we
looked at his serum albumin and his body composition, he was
already mildly malnourished.

Many physicians won't address nutrition because, "You look
fine -- your weight is stable." But what you can't see from
the outside is that there may be changes already occurring
with loss of muscle mass; it is being replaced with fat. You
may maintain your overall weight, while inside there are
changes leading you down the path to malnutrition. In our
chart review we found that 34% of patients were already
severely malnourished when they were hospitalized with their
first AIDS-defining illness, and another 46% were moderately
malnourished. It is clear that changes in nutritional status
occur during the relatively quiet phase of "just" being HIV-
positive.

ATN: How can we explain body composition to our readers, and
how can people keep an eye on that? Is an expensive test
needed, or are there simple ways?

KW: Body composition will tell us what lean/fat ratio you
have. This reflects your muscle mass and fat pads. Men will
have fewer fat pads than women.

In simple starvation the body will start breaking down the
fat as a source of energy, and then eventually go to the
muscle. With AIDS we're seeing the opposite: The body breaks
down the muscle and leaves the fat intact until later. So
there are metabolic derangements going on that we don't
understand well. Eventually in some people, no matter what
you do, unless you're on TPN [explained below], the body
won't be able to utilize the protein, carbohydrate and fat
you're giving it, to put into muscle and fat.

ATN: How do health care providers keep an eye on lean body
mass?

KW: One simple way is to use a small caliper and test 12
different sites on the body--pulling the skin and fat away
from the muscle and pinching, and adding all the numbers.
Then you look on a chart for age, sex, height, weight, etc.,
to estimate the percent of body fat for the individual. We
use that plus something we call the Futrex, a machine that
bounces infrared light off the arm and computes the percent
of fat, lean muscle, and water the individual has.

ATN: Can you explain more about the nutritional assessment?

KW: There are many things to consider. We look at serum
albumin -- your protein level. It has many important
functions in your body, but the problem of albumin is
affected by all kinds of things and may not be accurate.
Also, the albumin level measures your nutritional status from
three weeks ago. More sensitive indicators include pre-
albumin (which indicates nutritional status about three days
ago), and transferin, another protein, which is very
sensitive; it indicates where you were hours ago with your
nutritional status. We also look at triglycerides,
cholesterol and zinc. Other information that helps us
determine the level of malnutrition is the amount of weight
lost over a period of time, and the person's percentage of
usual body weight.

Getting Help Early

ATN: You've said that early, aggressive nutritional
intervention can prevent weight loss, increase the function
of the gut, reduce the chance for opportunistic infections,
enhance response to therapies and improve a person's quality
of life and sense of well-being. Can you define "early,
aggressive nutritional intervention" a little more?

KW: When somebody is first diagnosed as being HIV-positive,
they should sit down with a registered dietitian or someone
in the nutrition field and ask, where am I now? They should
align themselves with a physician and tell the doctor, I want
to maintain my weight, I want to keep an eye on this. Then,
as soon as they start losing weight, even if there are no
other symptoms or obvious causes, go to the doctor or
dietitian and ask, "Where am I with my body composition and
what do I do now?"

Through each change that goes on the person needs to be in
touch with a physician or someone who's going to be able to
give them some direction. The earlier we can get that weight
back up and keep an eye on body composition, the better off
we will be in prolonging nutritional status and quality of
life.

ATN: What can we say to people at an earlier stage now?

KW: Align themselves with a registered dietitian, not a
nutritionist. A nutritionist is someone who may have gone to
school or read books, but has never taken a test to confirm
their knowledge. A registered dietitian has had four years of
college, and many of them will go an extra year of training,
and there is a standard test they have to pass, so you know
their knowledge base is probably stronger. Their experience
and exposure to different types of patients is much more
structured and solid than the nutritionists. The nutritionist
may be good, but to get the total picture you should choose a
registered dietitian who is familiar with HIV disease or who
has worked with oncology patients, because there are many
similarities in certain aspects of the nutritional component.

People who are still feeling good when they find out they are
HIV-positive should talk with a registered dietitian and ask,
where am I now? How is my body composition -- what percent
fat? Am I overweight or underweight? Dietitians can help with
eating more healthy foods. It is recommended that people come
back occasionally, perhaps every three months, to check on
how things are going.

As soon as someone starts to lose weight, they should see the
doctor or the dietitian. There may be other things going on
at that point, or perhaps they may need to add a liquid
supplement. As with any health care provider, find a
dietitian you can communicate well with, whom you feel
comfortable with.

ATN: How does one find a registered dietitian?

KW: If you don't have a referral, the American Dietetic
Association has a list; or you can look in the yellow pages
for a registered dietitian.

ATN: Will insurance pay?

KW: At this point it's probably an out-of-pocket expense,
unless a physician is also seeing the person in the same
clinic. There is legislation underway now, though, to put
registered dietitians in the category of being licensed
practitioners, to facilitate payment by insurance.

ATN: What about people who can't afford a dietitian?

KW: It's a difficult situation. However, if somebody is
hospitalized for some reason, they can ask for a nutrition
consult and assessment from a registered dietitian or
nutritional team, and have that during their hospitalization.

Nutritional Status in HIV Disease

ATN: HIV related complications often occur in the lower
gastrointestinal tract. Can you explain why this is the case?

KW: Immune globulins in the gut -- a kind of antibody called
IgA -- normally act at the mucosal layer to protect against
invading organisms. When somebody is immunocompromised, the
body doesn't produce enough of the antibodies to be
protective. This creates open portals of entry in the gut for
bacteria, funguses and viruses. Critical care patients get
septic because they are not using their gut and they are
malnourished; these problems allow the translocation of
bacteria, etc., into a person's system. That's why we want to
keep the gut functioning as long as possible -- stimulate it
and keep those immune globulins and macrophages working, so
there isn't the opportunity for pathogens to enter.

ATN: What can be said about nutritional status as an
indicator for survival?

KW: Kotler's research found that when a person is at 66% of
their ideal body weight and 54% of their body cell mass, they
die.

People maintain a certain weight, then develop an
opportunistic infection and drop their weight. They may gain
weight back, but not quite up to what it was before. Another
opportunistic infection will continue the downward spiral.

That's why it is important to keep nutrition under control,
especially while you are in the hospital. This is one disease
where everybody has to be their own advocate; go to the
doctor and ask about this drug or that trial, pushing,
pushing, pushing. Most doctors consider weight loss and
malnutrition inevitable. That's one of the most frustrating
things for us -- getting the doctors to buy into the fact
that there is a lot we can do.

ATN: Please explain how to meet the specialized nutritional
needs of persons with mildly to severely symptomatic HIV
disease.

KW: There are nutritional formulas specifically designed for
altered-gut problems. For supplementation people can use
nutritional formulas which you can get over-the-counter at
pharmacies; they come in cans and are taken orally. More
severe clinical situations may require peripheral parenteral
nutrition (PPN), or total parenteral nutrition (TPN). These
are formulated for individual patients and administered
intravenously into the arm (PPN), or with a catheter in the
chest (TPN).

ATN: Give us some examples of when intravenous feeding is
appropriate.

KW: PPN is for short-term use because it will irritate the
veins fairly quickly; 7-10 days is usually the maximum. We
used it on a patient with CMV esophagitis so bad he couldn't
swallow his own saliva. It was used as a "bridge" until the
CMV treatment could kick in and the patient could swallow
again. Then we worked him into an appropriate diet. In a
different instance we used TPN for a patient who couldn't eat
because of an obstructing lymphoma of the stomach. We put him
on TPN for two weeks while he was getting chemotherapy and
radiation. The tumor melted, and then we could feed him
normally.

In another case, there was relentless, severe cryptosporidium
diarrhea -- 20 liters of stool per day. The patient would die
in days if we didn't do something to put the gut at rest. In
the first couple of weeks we used TPN to give the gut a rest.
Then we reintroduced food in the form of pure amino acids;
the product was Vivonex, a chemically-defined liquid diet
very low in fat, to stimulate the gut and some digestive
enzymes. Basically, the body doesn't have to do any work, the
nutrients just get absorbed across the gut mucosa. It's an
easy, sort of passive way to get food into someone.

One thing to consider is that people on TPN tend to gain fat
weight, while on tube feeding (see below) they tend to gain
more lean weight -- we think this is because it's more
physiologic to have food going directly into the gut.

In the case of TPN, it is important to discuss the rationale
for it, as well as end-points for its use, before it is
started. We have seen TPN help people "over the hump" and
improve their nutritional status. However, its drawbacks
include the possibility of infection, metabolic and technical
problems, and great expense.

ATN: Where can one get more information to help make these
decisions?

KW: The American Society for Parenteral and Enteral Nutrition
(ASPEN) is a multidisciplinary society of physicians,
pharmacists, nurses, and dietitians, who are specifically
interested in nutrition. They put out guidelines about when
TPN should be used, when it would be helpful, when it's not a
good idea.

What Is Tube Feeding?

Tube feeding is a less expensive and more "normal" method of
feeding someone than PPN or TPN, because you use the
gastrointestinal tract. Tube feeding would be appropriate for
someone with a normal stomach and gut function, but who had
either dysphagia (difficulty in swallowing) or odynophagia
(pain on swallowing). The feeding could be given
continuously, or just at night to allow freedom to move about
during the day.

There is a wide range of formulas and ingredients for tube
feeding, for example: (1) intact protein and high fat and
carbohydrate; (2) various other forms of protein such as
peptides or pure amino acids for compromised gut function;
(3) medium chain triglycerides, a form of fat that is easily
absorbed; (4) fiber; (5) fish oils, etc. The registered
dietitian, working with the physician, can make the best
recommendation for each individual.

[Part II of this interview will look at liquid nutritional
supplements, oral rehydration salts, vitamins, and other
topics.]


***** California: MediCal Cut in Monthly Prescription
      Allowances Starting Oct. 1

by Rae Trewartha

The 1994 California State budget once again reduced the
prescription allowance for MediCal patients -- starting
October, 1 the limit will be six per month without prior
approval. In 1977 the previous limit of two prescriptions per
month was changed to allow an unlimited number; however, the
1992 California State budget reduced this allowance to ten.
But the limit of ten did not come into force until July 1 of
this year, when an on-line billing system for pharmacies was
set up by MediCal. The new limits could have a serious effect
on people with severe illness, including AIDS.

Prescriptions over the limit can be requested through a
Treatment Authorization Request (TAR), a one-page form which
is otherwise used to allow prescriptions of drugs which are
not on the MediCal formulary. A doctor or pharmacist can
complete a TAR which, if it is granted by the MediCal Field
Office, will allow the patient to acquire the drug in 3-5
days (urgent TARs can be phoned or faxed in and should be
processed within 24 hours). However, many doctors and
pharmacists will not deal with TARs. If their request is
refused by MediCal, it can be resubmitted, but this will take
another 3-5 days.

If you do not obtain approval for the drug in this way, you
can apply to your county AIDS Drug Assistance Program (ADAP).
If the drug is not available on that program, or if you are
refused it, you might ask your physician whether the company
who manufactures it has a patient assistance program; for a
partial list of available programs see AIDS Treatment News
#186, November 5, 1993.

San Francisco is trying to set up a system to automatically
refer rejected MediCal requests to the county ADAP program,
which could reimburse the pharmacy. However, only certain
pharmacies are enrolled in the ADAP program. Also, this San
Francisco proposal has not yet been approved by the state.

The ADAP requires that the supply of a drug to a MediCal
patient be approved on an annual basis, except where the
patient has a higher income than the MediCal limit and is
thus required to pay a share of the cost of prescription
drugs. For these "share of cost" patients, approval must be
applied for on a monthly basis and is based on income. TARs
can be also be approved for up to 12 months and, according to
Len Terra at the MediCal Benefits Branch, this is the usual
case for chronic drugs such as AZT. For other drugs, however,
the patient may have to submit a TAR each month, and ADAP
will never authorize more than a 30-day supply of a drug at
any one time.

Len Terra says the MediCal field offices have already
experienced an increase in TARs as a result of the ten-
prescription limit and they are employing more processors to
handle the further increase they expect after October 1. The
ADAP also expects a large increase in requests but is
confident of being able to handle the paperwork involved.
Money to fund ADAP, though, is provided by each county and
there is concern that there will not be enough funding to
cover what is expected to be a large increase in demand for
medications.

MediCal patients are now faced with a situation which could
endanger their health. Many people with AIDS are taking more
than six drugs, and it is not certain that they will obtain
the necessary TARs to keep up all their treatments. Ed
Miller, at Castro Village Pharmacy in San Francisco, suggests
that if you are prescribed more than six drugs, you could ask
your doctor or pharmacist to apply for TARs for the drugs you
are taking chronically, as these are likely to be approved
for a year and save you the trouble and worry of having to
apply each month.

Also, note that MediCal allows medications (apart from three
or four abusable-type drugs) to be dispensed in amounts up to
100 days' supply; if your doctor thinks you are likely to
need a drug for this length of time, he or she should
prescribe it in this amount. Then you could get another drug
on your allowance of six, for the next two months.

MediCal patients need to make sure their doctors and
pharmacists are aware of the new regulations, and that they
are willing to help them obtain the medications they need.
People we spoke to were still unsure how the regulations
would be imposed, and how difficult it will be for patients
to get TARs approved. As we went to press, however, the
Department of Health Services scheduled a meeting to discuss
the possibility of exemptions for people with AIDS. We will
inform you of the outcome.


***** Announcements, Notes

** Kaposi's Sarcoma -- Major Overview Published

The KS Project Report: Current Issues in Research & Treatment
of Kaposi's Sarcoma, an 85-page report by Michael Marco with
Marty Majchrowicz, covers all aspects of conventional
treatments, experimental treatments, epidemiology,
pathogenesis, and research -- what is being done in KS
research, and how its funding and organization need to be
improved. The authors are treatment activists who had
assistance from leading oncologists; they also interviewed 25
oncologists, dermatologists, radiation oncologists, primary
care physicians, and laboratory workers who have extensive
experience with AIDS-related KS. The information is very
current, as the report was completed rapidly and published in
late July 1994 by the Treatment Action Group (TAG).

Copies are available from TAG, 147 2nd Ave., Suite 601, New
York, NY 10003, 212/260-0300. A $10 donation is requested to
help cover cost, but no one will be denied the report for
lack of funds.

** Interim AIDS Coordinator Announced

On August 2, Patricia S. Fleming was appointed interim AIDS
coordinator by President Clinton. Ms. Fleming is currently
special assistant to Health and Human Services Secretary
Donna E. Shalala. She previously served as administrative
assistant to the late Ted Weiss (D-NY), specializing in AIDS
and public health issues.

According to an August 2 press release from the White House,
Fleming "said she expects the interim appointment will last
less than two months and that she is not a candidate for the
permanent appointment."

** Medical Marijuana: 89 Percent Support

An informal telephone poll of over 50,000 people, conducted
by Parade Magazine and published in the July 31 issue, found
that 89 percent believed that marijuana should be legal for
medicinal purposes. This was not a scientific poll which
selected people randomly, but consisted of callers who
responded to the June 12 Parade Magazine cover article,
"Should Marijuana Be Legal?" (It may be no less important as
a measure of public opinion, however, because it counted
people who cared enough about the issue to take the action of
calling in.)

For more information on medical marijuana, contact the
Alliance for Cannabis Therapeutics, P.O. Box 21210, Kalorama
Station, Washington, DC 20009, 202/483-8595.

** Correction -- Zerit (d4T) Information Number

AIDS Treatment News #203 gave an information number for
physicians to call to obtain information about enrolling
patients in the parallel track program for access to d4T,
which is continuing for a short time, despite approval of the
drug, because of a delay in availability of commercial drug
supplies. Due to a typographical error, the phone number we
published was incorrect. The correct number is 800/842-8036.

[Note: The latest information from Bristol-Myers Squibb is
that Zerit may be available in pharmacies starting the second
week in August. In that case, new enrollment in the parallel-
track program will probably close later in August, with those
in the program continuing to receive the drug for about one
month after new enrollment closes.]



***** AIDS TREATMENT NEWS
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AIDS Treatment News reports on experimental and
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Treatment News does not recommend particular
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ISSN # 1052-4207

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