AIDS TREATMENT NEWS Issue #355, November 17, 2000
phone 800-TREAT-1-2, or 415-255-0588

CONTENTS:

** Community Update: New Drugs to Watch
A report on two recent conferences summarized some of the
most important treatment changes today, new drugs in the
pipeline especially for patients who have already failed
many antiretrovirals, and current treatment philosophies
and challenges for AIDS medicine and research.

** Nevirapine (VIRAMUNE(R)) Strengthens Warning on Liver,
Skin Toxicities
A recent letter to doctors strengthened the U.S. warnings
and precautions on using this antiretroviral (which has
been approved and in widespread use for years), due to
serious complications in a small minority of patients; the
point of the changes is to catch such problems and stop the
drug in time. Patients obtaining refills or new
prescriptions should in the future receive a "patient
package insert," dated November 2000, based on the new
warnings.

** "Trizivir" Approved: Three Existing Drugs in One
New approval combines AZT, 3TC, and abacavir in one pill.

** Nutrition and HIV Infection: Experience in Zimbabwe--
Interview with Lynde Francis
For years Lynde Francis has run an AIDS service
organization in Harare, Zimbabwe, where few patients can
afford antiretrovirals, so nutritional improvement is often
the only treatment available. In this interview she
explains what she has found to be helpful. While specific
nutritional advice will vary, depending on many factors, we
believe that readers should be aware of this treatment
experience.

** AIDS TREATMENT NEWS Will Move to Philadelphia on January
2
At the end of this year AIDS TREATMENT NEWS will move to
Philadelphia to work with Philadelphia FIGHT, a well-known
AIDS treatment, research, and education organization. Our
policies and publication schedule will remain the same, and
readers will see little immediate change except for the
address.


***** Community Update: New Drugs to Watch

On November 6 a community forum, "HIV Therapy Update from
the Recent ICAAC and Glasgow Meetings," was sponsored by
three San Francisco AIDS organizations (the Conant
Foundation, the San Francisco AIDS Foundation, and the AIDS
Research Institute of the University of California San
Francisco); unlike most medical meetings, this one was
funded by the organizations themselves without seeking
pharmaceutical-company support. Here are a few bottom-line
treatment messages that we found most important:

* The medical community is favorably impressed with Kaletra
(lopinavir, formerly ABT-378, the newly-approved "second
generation" protease inhibitor. A major Abbott trial
presented 24-week data at ICAAC (40th Interscience
Conference on Antimicrobial Agents and Chemotherapy,
Toronto, September 17-20, 2000) and some 48-week data at
the Fifth International Congress on Drug Therapy in HIV
Infection (Glasgow, UK, October 22-26, 2000); complete 48-
week data will be available at the Retroviruses conference
(8th Conference on Retroviruses and Opportunistic
Infections, Chicago, February 4-8, 2001). Stephen Becker,
M.D., noted the impressive results with patients who were
highly treatment experienced (but naive to the NNRTI class
of antiretrovirals, in this trial). Also, very few patients
discontinued the trial because of toxicity or because of
virologic failure. Even patients with substantial
resistance to other protease inhibitors were likely to do
well.

Doctors do not agree on whether to reserve this drug for
"salvage" therapy when other treatment options have failed,
or to use it earlier in treatment, perhaps in initial
therapy. At least at this time Dr. Becker chooses to wait
and use it later.

Also, the development of Kaletra has been important as a
"proof of concept" for the strategy of using a low dose of
ritonavir (Norvir(R), another protease inhibitor from
Abbott Laboratories) in order to keep another protease
inhibitor in the body longer (by blocking a liver enzyme
which destroys these drugs). Kaletra has the ritonavir
included in the formulation, as it must be used with
ritonavir or it would be eliminated from the body too
quickly.

* Steven Deeks, M.D., discussed some of the most promising
new HIV drugs in the pipeline. He named four: T-20,
tipranovir (a new kind of protease inhibitor), DAPD, and
tenofovir. All of these are active against many viruses
which are highly resistant to other drugs.

He also noted that there is now much excitement about HIV
integrase inhibitors, a major target for new drugs. But
these are farther away, probably about five years from
widespread use.

* Paul Volberding, M.D., discussed some of the major
challenges of HIV research today, including acute infection
(finding the cases is a challenge), finding people who are
not currently in care so that they can be offered
treatment, when to start antiretroviral therapy (the
medical community has backed off from the "hit early" part
of "hit hard, hit early"--but still treats hard, once one
does start antiretrovirals). A survey of very experienced
HIV physicians in San Francisco found that most started
treatment at a CD4 count averaging around 350 (and some as
late as a count of 200)--depending on other information
about the patient, of course. The survey also found that
combinations including the NNRTI drug class were the most
popular to start with [as opposed to either protease
inhibitors, or the triple nucleoside analog treatment with
abacavir].

[Note that this community forum took place in November
2000, and treatment strategies later will be different.
Sometimes our articles circulate on the Internet forever
and are read as fresh information after they are no longer
applicable.]

Other talks at the forum reviewed progress in preventive
vaccines, and in microbicides to prevent HIV transmission.


***** Nevirapine (VIRAMUNE(R)) Strengthens Warning on
Liver, Skin Toxicities

On November 9 Boehringer Ingelheim Roxane Laboratories
notified medical professionals that the FDA-required
labeling for its drug nevirapine had strengthened its
warnings about risks of liver and other toxicities, due to
reported cases of serious or fatal reactions to the drug.

All future U.S. prescriptions and refills of nevirapine
should come with a new patient package insert, which will
tell patients what they most need to know to use the drug
safely--including a description of symptoms which should
lead to an immediate call to one's physician, who may
decide to stop the drug permanently.

The first 12 weeks on nevirapine is especially critical, as
about two thirds of the reactions have happened in that
period. Also, the letter recommends that prednisone should
not to be used to prevent nevirapine-associated rash, as a
clinical trial found that this made the problem worse.

The full text of the letter to medical professionals is on
an FDA Web site at:
http://www.fda.gov/medwatch/safety/2000/virahp.pdf

Some of the warnings:

"*...Although clinical presentation varied among patients,
frequently occurring features included non-specific
prodromal signs and symptoms of fatigue, malaise, anorexia
and nausea, with or without abnormal serum transaminase
levels. In these reports, symptoms progressed to jaundice,
hepatomegaly, elevation of transaminase levels and
hepatitic failure over a period of several days. Patients
with signs or symptoms of hepatitis must immediately seek
medical evaluation, have liver tests performed, and be
advised to discontinue VIRAMUNE as soon as possible.

"* Based on these reports, the first 12 weeks of VIRAMUNE
therapy are a critical period during which intensive
clinical and laboratory monitoring, including liver
function tests, is essential to detect potentially life-
threatening hepatotoxicity and skin reactions. [emphasis in
original]

"* Although most serious hepatitic events occurred during
the first 12 weeks of VIRAMUNE therapy, approximately one-
third of cases have been reported to occur after this
critical period.

"* The optimal frequency of monitoring during the first 12
weeks of therapy with VIRAMUNE has not been established.
Some experts recommend clinical and laboratory monitoring
more often than once per month, and in particular, would
include monitoring of liver function tests at baseline,
prior to dose escalation and at two weeks post dose
escalation. After the initial 12-week period, frequent
clinical and laboratory monitoring should continue
throughout VIRAMUNE treatment.

"* Increased AST or ALT levels and/or a history of chronic
hepatitis (B or C) infection are associated with a greater
risk of hepatitic adverse events.

"*Serious hepatotoxicity, including liver failure requiring
transplantation in one instance, has been reported in HIV-
uninfected individuals receiving multiple doses of VIRAMUNE
in the setting of post-exposure prophylaxis, an unapproved
use.

"*If clinical hepatotoxicity occurs, VIRAMUNE should be
permanently discontinued and not restarted after recovery."

"In summary, the need for careful clinical and laboratory
monitoring of patients receiving VIRAMUNE must be
emphasized. The diagnosis of hepatotoxicity should be
considered for patients presenting with non-specific
symptoms of hepatitis even if liver function tests are
normal or alternative diagnoses are possible. These
considerations are especially critical during the first 12
weeks of therapy, when serious liver toxicity occurs most
frequently, but remain important throughout treatment with
VIRAMUNE."

Comment

Nothing in this letter addresses use of a single dose of
nevirapine to prevent mother-to-infant transmission of HIV;
these toxicities occurred in patients taking multiple
doses. Nor does the warning imply that the risk with this
drug is greater than with other antiretrovirals. If any
antiretroviral combination had a significantly better
safety and efficacy profile than the alternatives, then
those alternatives would not be used.

This warning underlines the need for care in using all
anti-HIV drugs, the need for the development of better
drugs, and the need for more creative research into why the
various toxicities occur, how to predict which patients are
most vulnerable to which drugs, and better ways to prevent
the problems from developing.


***** "Trizivir" Approved: Three Existing Drugs in One

On November 15 the FDA approved Trizivir(R), a product that
combines adult doses of three previously approved Glaxo-
Wellcome drugs -- AZT, 3TC, and abacavir -- into a single
tablet. The rationale is that taking only one tablet twice
a day without regard to food may improve adherence in some
patients. Some activists are concerned that this treatment
might be chosen for institutional convenience (for example
when treating prisoners) even when it is not the best
medical option for the individual.

The following writeup was released November 15 by the AIDS
Treatment Information Service, an agency which provides
AIDS treatment information for the U.S. government:

"November 15, 2000: The Food and Drug Administration (FDA)
today approved Trizivir for the treatment of HIV in adults
and adolescents. Each dose of Trizivir is a fixed-dose
combination of Ziagen (abacavir/ABC), Retrovir
(zidovudine/AZT), and Epivir (lamivudine/3TC), three
nucleoside reverse transcriptase inhibitors (NRTIs) already
approved by FDA. Trizivir is not recommended for treatment
in adults or adolescents who weigh less than 40 kilograms
because it is a fixed-dose tablet.

"Because Trizivir combines a single dose of three drugs
into one pill, it may be easier for some patients to comply
with their medication regimen. Each component of Trizivir
is also available separately. This combination product
should only be used by those whose treatment regimens would
otherwise include these doses of these three nucleoside
analogues. It may be used alone or in combination with
other antiretroviral agents for the treatment of HIV
infection, but should not be administered concomitantly
with abacavir, lamivudine, or zidovudine, which are already
contained in Trizivir. The recommended dose is one tablet
twice a day.

"For more information, contact our ATIS Health Information
Specialists at 1-800-448-0440 or at atis@.... You
can find the complete FDA press release at
http://www.hivatis.org/atisnew.html "


***** Nutrition and HIV Infection: Experience in Zimbabwe--
Interview with Lynde Francis

by John S. James

Lynde Francis is the founder and director The Centre, in
Harare, Zimbabwe, an organization run by and for people
living with HIV. She is also the regional contact for
Southern Africa for the ICW, the International Community of
Women Living with HIV and AIDS. We met Ms. Francis several
years ago in San Francisco, and interviewed her for this
article in Durban, South Africa on July 13, 2000.

These suggestions developed from her experience in
Zimbabwe; we do not suggest that they be applied literally
or mechanically in very different environments, such as the
U.S. But we do believe her results and experience are worth
knowing.

* * *

AIDS TREATMENT NEWS: What are some of the most important
lessons you have learned about nutrition and HIV treatment,
both for Africa and elsewhere?

Lynde Francis: In the developing world, nutrition is often
the only form of therapy available. We have learned that
with correct nutrition, which includes vitamin
supplementation and a holistic approach to HIV, you can
maintain health almost indefinitely if you start early
enough. And if you start when someone is already ill,
nutrition together with treatment of opportunistic
infections can put them back on their feet and back in
employment.

Also, when people are on pharmaceutical treatment,
nutrition supports them; you can use nutrition as a way of
avoiding side effects, and reconstituting the immune system
together with the drugs.

ATN: What approaches to nutrition do you recommend?

Francis: The rule of thumb is unrefined, unprocessed foods,
low fat, no sugar, and avoiding stimulants like caffeine.
By unrefined food I mean, if you eat bread, it should by
whole wheat bread; if you eat rice, it should be
unpolished, brown rice. If your staple is maise meal, as it
is in many parts of Africa, it should be stone ground maise
meal. It could include other grains like rye, like wheat
used as a rice which is delicious; it could include
sorghum, which is the traditional grain which was used
throughout Africa before maise came in.

The proteins you take in should be as much as possible
beans, lentils, peas, nuts, soya proteins, plus chicken and
fish. Pork should be avoided, and fatty beef products
should be avoided.

As far as possible avoid foods that have additives, like
coloring, flavoring, or preservatives. And eat foods which
are fresh and preferably indigenous, grown where you live.
It's a rule of thumb that if it grows locally, it's going
to be good for you and it's going to be appropriate because
it will grow at the right season.

Clean water of course is an absolute must; so if you don't
have access to clean water, it's vital that you properly
filter, purify, or boil.

We recommend a low-fat diet. One of the big exceptions to
that is yogurt. Yogurt is like a magic food, as is garlic.
Yogurt helps to control thrush. Sugar feeds thrush, so we
advise people to cut sugar out of their diet as much as
possible.

Garlic is a natural antibiotic and antiviral.. It is also
extremely good for thrush. And you can use it for vaginal
as well as for oral thrush.

We recommend that food be prepared freshly if possible, and
that much of the vegetable and fruit intake be raw--salads
and raw fruit and vegetables, which maintains all the
vitamin and mineral content. At least 30% of your intake of
food daily should be vegetables and fruits. Fifty percent
should be whole grains. Fifteen percent should be proteins.
And then 5% is the cherry on the cake--it's whatever else
you want, avocados, cheese and eggs--with a proviso that
when you have diarrhea, you should avoid dairy products,
and avoid all fat.

We mostly use locally available treatments in Africa,
because usually we don't have access to drugs. For example,
aloe vera is wonderful for herpes sores; slit the leaves
open, and the gel inside, when applied to sores and itching
of shingles, is miraculous. Another herb that's very good
for this condition is comfrey, making a poultice of comfrey
leaves.

We teach people in Africa recipes that are useful in
difficult times, like when you have diarrhea and wasting.

It is harder to teach good nutrition in the developed
world. In Africa we do not have three generations of junk
food to deal with. We all can remember our traditional
cuisine. In European countries and the U.S., this is more
difficult.

You need to think in terms of the five rules: unprocessed,
unrefined, low fat, no sugar, and one other rule, which is
little and often. It is more applicable to people who have
wasting, but it's applicable to anybody who wants to keep
up their appetite, which is to take small, attractive meals
more often. Rather than large heavy meals twice a day, take
small meals five times a day. Those are the basic rules.

ATN: Where can our readers get more information?

Francis: We have a booklet, Food for People Living with
HIV, which is applicable everywhere in the world. It has
recipes, it has a vitamin and mineral chart, it gives the
kinds of herbs and spices that can be used as therapies--
what's cooling, what's heating, remedies that can be used
to treat sores.

ATN: What vitamin and mineral supplements do you include?

Francis: We call it ZACES; that's an acronym that we
developed to help people remember the vitamins and
minerals. It's zinc, vitamin A, vitamin C, vitamin E, and
selenium. We call this the infection fighting, immune
boosting combination. We recommend that all our patients
take supplements of these. Even an adequate food intake is
not enough to deal with the level of immune suppression
that happens in HIV disease. We give them diet sheets, and
recommend that the supplements be taken in a balance.

ATN: For the vitamin A, could they use beta carotene
instead? I am reluctant to suggest vitamin A, because
people might take too much.

Francis: We have a problem getting beta carotene, because
it is very expensive for us. So we recommend that they take
vitamin A. It really works--especially when it is
supplemented with 20 mg of zinc daily, which is very cheap
for us to get.

ATN: What is the mission of your organization (The Centre,
in Harare, Zimbabwe)?

Francis: Our mission, basically, is to teach long-term
survival techniques to people living with the virus, based
on nutrition and a holistic approach.

I urge people to look more to nutrition as an adjunct to
therapy, or as an alternative to therapy. It's amazing the
resuscitation that we see--people who come in and they are
terminally ill, and you put them onto an adequate nutrition
regime and give them vitamin supplements, and it's like
Lazarus, it's like the way people describe what happened
with the antiretrovirals. We have seen people recover
completely just from getting their nutrition intake
adequate, and getting help on coming to terms with and
managing their disease.


***** AIDS TREATMENT NEWS Will Move to Philadelphia on
January 2

by John S. James

Starting January 2 AIDS TREATMENT NEWS will publish from
Philadelphia, Pennsylvania, where we will work closely with
Philadelphia FIGHT, a well-known AIDS treatment, research,
and information organization. I will remain in complete
control of the content of this newsletter, and readers will
notice little immediate change except for the new address
and phone numbers.

This move offers many advantages:

* Philadelphia FIGHT (http://www.fight.org) is an
excellently run organization which includes: the Jonathan
Lax Treatment Center, an HIV clinic for persons of all
income levels; community-based clinical trials funded by
the CPCRA program of the U.S. National Institutes of
Health; Critical Path AIDS Project, an AIDS treatment and
computer-access organization founded by Kiyoshi Kuromiya
and continuing after his death; the AIDS Library, open to
the public at Philadelphia FIGHT and by phone; and project
TEACH, which trains peer educators in AIDS treatment
information. Working with an organization with such diverse
hands-on AIDS treatment, research, information, and
outreach experience can help us develop articles, fact
sheets, and other resources which are widely useful.

* From Philadelphia it will be much easier to attend
meetings in the Washington, New York, and Baltimore areas--
a convenient two-hour train ride with comfortable seating
and power for a laptop.

* Working with FIGHT will greatly reduce the overhead of
running the AIDS TREATMENT NEWS office in pathologically
expensive San Francisco, enabling me to focus on research
and writing instead of paperwork and making ends meet. We
have learned that excessive overhead--the cost (in money,
time, or other resources) of just getting by--is more
destructive than generally realized.

AIDS TREATMENT NEWS has always had primarily a national
focus with some international coverage, and this will
continue. We have also included San Francisco area news,
because we had more readers there and knew that area better
than elsewhere; this too will continue, as we still have
many readers and contacts there, and will return several
times a year for conferences and other visits. We will also
increase our Philadelphia coverage, in coordination with
the Critical Path AIDS Project newsletter, which for years
has published in-depth Philadelphia information along with
national treatment articles. Both newsletters will continue
as separate publications.

Our current phone numbers will work through December, then
the local (area 415) numbers will have referral messages to
the new Philadelphia numbers. We already have a new U.S.
toll-free fax (and voicemail) number which will reach us
anywhere: 1-800-273-7168; we will keep it at least through
the transition. Faxes concerning AIDS TREATMENT NEWS
business should be sent to this number starting now; press
releases and other general faxes should be switched to
email and sent to jjames@.... Due to the move, we will
have shorter office hours during December, but messages
can be left any time 24 hours a day.


***** AIDS TREATMENT NEWS

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Editor and Publisher: John S. James
Associate Editor: Tadd T. Tobias
Reader Services: Tom Fontaine

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 that work for
them. AIDS TREATMENT NEWS does not recommend particular
therapies, but seeks to increase the options available.

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ISSN # 1052-4207

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