AIDS TREATMENT NEWS Issue #361, February 28, 2001
phone 800-TREAT-1-2, or 215-546-3776

CONTENTS

** Retroviruses Conference: Johns Hopkins Report
On March 1 the HIV newsletter from Johns Hopkins University
published several short, focused reports on the
Retroviruses conference, written primarily for physicians.
These are available on the Web or by mail. We list most of
the major topics covered.

** Obtaining the New HIV Treatment Guidelines
How to order the new HIV/AIDS official adult treatment
guidelines by mail if you do not have computer access; how
to get your questions about treatments answered at the same
office; and other guidelines available including prevention
of opportunistic infections, and what to do in case of
occupational exposure to HIV. In addition, the official Web
site for the guidelines has a marked copy which shows where
the current adult guidelines are changed from the previous
version.

** Merck, Bristol-Myers Squibb Announce Major Price
Reductions for Poorest Countries: Major Access Progress but
Questions Remain
Two major pharmaceutical companies have announced new and
much lower prices for antiretrovirals for African and some
other poor countries, along with a uniform pricing policy
which should simplify negotiations for access to the drugs.

** MSF (Doctors Without Borders) Petition Against South
Africa Lawsuit, Deadline April 15
Doctors Without Borders is collecting signatures from
around the world, asking major pharmaceutical companies to
drop the lawsuit which for three years has prevented South
Africa from implementing its post-Apartheid reform of its
medicines law.

** Southern Africa Home Care: Conference Report
These Web reports of a recent conference in Gabarone,
Botswana, provide an African view of the epidemic and the
home-care approaches now in use.

** AmFAR Seeks Medical Writer/Editor in New York


***** Retroviruses Conference: Johns Hopkins Report

by John S. James

The March 1, 2001 issue of THE HOPKINS HIV REPORT has
several short, focused summaries of some of the important
treatment information from the recent Retroviruses
conference (8th Conference on Retroviruses and
Opportunistic Infections, Chicago, February 4-8, 2001).
Written "for practitioners caring for patients with
HIV/AIDS," it can also inform patients who have educated
themselves about the disease. Because it targets busy
people, the articles are short and to the point. This issue
of THE HOPKINS HIV REPORT focuses heavily on
antiretrovirals, and also includes an important section on
hepatitis C.

Other major topics include the new treatment guidelines
(see "Obtaining the New HIV Treatment Guidelines" in this
issue), new antiretrovirals in development, when to start
antiretroviral therapy, treating experienced patients, drug
concentrations and interactions, adherence, and women's
issues.

A table of contents with links to each of the articles is
at:
http://hopkins-aids.edu/publications/report/mar01_toc.html

For those without Web access, here are instructions for
ordering by mail: "THE HOPKINS HIV REPORT is available for
free upon request. All requests to be added to our mailing
list should include complete mailing information and be
sent to: THE HOPKINS HIV REPORT P.O. Box 5252, Baltimore,
MD 21224, Attn: Distribution. Change of address should be
mailed to the address listed above as well. All other
correspondence should be sent to Mary Beth Hansen, Managing
Editor, THE HOPKINS HIV REPORT, JHU Division of Infectious
Diseases, 2700 Lighthouse Point East, Suite 220, Baltimore,
MD 21224."

Some Highlights of the Johns Hopkins Retroviruses
Conference Issue

* "New Antiretroviral Agents" by Joel E. Gallant, M.D.,
M.P.H., summarizes many of the potential new
antiretrovirals discussed at the conference -- including
some still in laboratory testing, some in clinical trials,
and a few in expanded access. You can get more information
about any particular drug by searching for it by name in
the abstracts of the Retroviruses conference
(http://www.retroconference.org -- choose Conference
Abstracts to get a search screen for the current year's
conference; also, you can usually find an abstract by
number through a search for the number) -- or in other
databases, such as the National Library of Medicine,
http://gateway.nlm.nih.gov, or AEGIS, (AIDS Education
Global Information System), http://www.aegis.org

The drugs are categorized as follows (the examples here are
not complete lists):

-NRTIs: Emtricitabine (FTC), DAPD, ACH-126,443

-NNRTIs: Capravirine, TMC-120, DPC 083

-Nucleotide Reverse Transcriptase Inhibitors: Tenofovir

-Protease Inhibitors: Tipranavir, BMS 232,632, Mozenavir
(DMP-450), GW433908

-Entry Inhibitors: These include attachment inhibitors (for
example, PRO-542), coreceptor (chemokine) antagonists (AMD-
3100, SC-351125 (SCH-C), SCH-D, and PRO-140), and fusion
inhibitors (T-20, T-1249)

-Integrase Inhibitors: S-1360

* "New Guidelines for the Use of Antiretroviral Agents in
HIV-Infected Adults and Adolescents," by John G. Bartlett,
M.D.

"For most clinicians caring for HIV-infected patients, the
most useful aspect of the guidelines will be the tabular
information on recommended regimens, food restrictions,
side effects, side effect monitoring, recommendations for
managing [drug] class adverse reactions, and dose
recommendations for combination therapy."

The article also includes this note, which emphasizes the
importance of seeing an HIV-experienced physician for one's
care:

"A preliminary study by the AETC National Resource Center
[AIDS Education Training Centers, http://www.aids-ed.org/]
indicates that about 98% of physicians with more than 20
HIV-infected patients are aware of these guidelines, and
96% have read at least part of them. However, among
physicians with less than 20 HIV-infected patients, only
71% had heard of the guidelines, and only 52% had read at
least part of them."

Also see "When Should Highly Active Antiretroviral Therapy
Be Initiated," by Timothy R. Sterling, M.D., in the March 1
Hopkins report. It discusses studies presented at the
Retroviruses conference that contributed to the decision to
recommend later treatment in the new guidelines --
including at least three separate studies which found an
increased risk of death among those who waited too long and
started treatment at a CD4 count under 200.

* "Antiretroviral Therapy: Naive Patients and Early
Therapy," by Joel E. Gallant, M.D., M.P.H., includes many
reports on individual drugs, developments in once-daily
therapy, and when viral "blips" during therapy may be
important.

* "Treatment of the Antiretroviral-Experienced Patient," by
Gregory M. Lucas, M.D., looks at:

- salvage options for patients with failure of highly
active antiretroviral therapy (HAART)

- switches from protease inhibitor (PI)-based regimens to
PI-sparing regimens as a strategy to simplify therapy or
minimize toxicity

- cross-resistance among nucleoside analogs

- "continuing HAART in the setting of persistent viremia."

* The section on drug interactions and pharmacokinetics
("Drug Transporter, Drug Concentrations, and Drug
Interactions," by Adriana Andrade, M.D., M.P.H. and Charles
Flexner, M.D., included:

- An overview of the complex but potentially important
research on P-glycoprotein (P-gp), a molecular "pump" that
can remove drugs from cells, preventing the drugs from
working. Inhibitors of P-gp are being developed for cancer
and other treatment. But P-gp appears to interfere with HIV
as well as with drugs, meaning that inhibiting it could
have both wanted and unwanted effects.

- A garlic supplement [taken twice a day for over two weeks
in this study] was found to greatly lower the blood level
of saquinavir (Fortovase(R)), to about half of what it had
been without the garlic. The mechanism is not known, and it
is not know what other drugs may be affected. For now,
patients are being cautioned about using garlic supplements
if they are taking protease inhibitors -- especially if
they are using a regimen with saquinavir as the sole
protease inhibitor.

- A study of indinavir (Crixivan) blood levels in patients
using marijuana [4% THC cigarettes three times a day for 14
days] in the marijuana clinical trial at the University of
California San Francisco found that indinavir levels may be
decreased. But only one of the values was statistically
significant, and no recommendations for changes in therapy
were made.

- A test of how well laboratories in the U.S. and Europe
measure blood levels of antiretroviral drugs found
generally poor quality, [with only one of 13 labs tested
being within 20% of the true value for all tests, and one
result being off by 10 times; see Retroviruses abstract
#734]. A quality-control program was recommended.

* "Women's Issues," by Jean R. Anderson, M.D., included new
findings on reducing perinatal transmission, indications
that HAART antiretroviral therapy may help improve outcome
in cervical dysplasia, and discussion of the serious
problem of increased incidence of some drug toxicities in
women.

THE HOPKINS HIV REPORT also includes sections on hepatitis
C co-infection (and hepatitis B), and on adherence. These
are difficult to summarize. Hepatitis C received much
attention at this conference. It is probably the most
important co-infection today in persons with HIV [at least
in the U.S.]. HIV accelerates progression of hepatitis C,
and liver disease due to hepatitis C is becoming an
increasingly important cause of illness and death in
persons with HIV.


***** Obtaining the New HIV Treatment Guidelines

The new GUIDELINES FOR THE USE OF ANTIRETROVIRAL AGENTS IN
HIV-INFECTED ADULTS AND ADOLESCENTS were released February
5; they are available at many Web sites, but the official
site for all the U.S. Department of Health and Human
Services HIV treatment guidelines is the HIV/AIDS Treatment
Information Service, http://www.hivatis.org

For a printed copy, you can call 800-448-0440, or mail a
request to HIV/AIDS Treatment Information Service, P.O. Box
6303, Rockville, MD 20849-6303. Note: it will probably take
the office 7-10 days to ship a printed copy of the
guidelines -- in addition to the time required for mail
delivery. Be sure to ask for the adult guidelines if that
is what you want, as there are currently five different HIV
guidelines available (see below).

The official Web site (http://www.hivatis.org) also has a
separate copy of the new adult guidelines with changes
highlighted in yellow, so you can see what is different
from the last version.

When we checked this site in March 2001, the guidelines
could either be viewed while online or printed; however, we
were unable to save a copy of the file for viewing on the
computer when not connected to the Internet. A dial-up (low
speed) connection did work OK for viewing. When we checked,
the HTML (Web) format version had a summary of the changes,
which was not included in the PDF format or printed
document.

What Has Changed?

The most prominent change is that the new guidelines are
more conservative about when to start treatment.

"In general, treatment should be offered to individuals
with fewer than 350 CD4+ T cells/mm3 or plasma HIV RNA
levels exceeding 30,000 copies/mL (bDNA assay) or 55,000
copies/mL (RT-PCR assay). The strength of the
recommendation to treat asymptomatic patients should be
based on the willingness and readiness of the individual to
begin therapy; the degree of existing immunodeficiency as
determined by the CD4+ T cell count; the risk of disease
progression as determined by the CD4+ T cell count and
level of plasma HIV RNA; the potential benefits and risks
of initiating therapy in asymptomatic individuals; and the
likelihood, after counseling and education, of adherence to
the prescribed treatment regimen." (From the Summary. This
discussion does not apply to all patients -- see the full
Summary.)

There is also a new section in this edition of the adult
treatment guidelines, "Considerations for Antiretroviral
Therapy in Women."

Since most HIV physicians were already treating in
accordance with the new guidelines even before their
publication, this recommendation is not expected to change
HIV practice very much. More important to day-by-day
medical care will be the extensive practical information
for physicians, which has been provided in 24 tables in the
document. The guidelines committee presented this
information as tables because members thought physicians
would be more likely to use it in that form than if
presented as text.

Other Guidelines Available

Besides the adult guidelines, the HIV/AIDS Treatment
Information Service can send current guidelines on:

* Prevention of opportunistic infections;

* Treatment of HIV in children;

* Prevention of mother-to-child transmission; and

* Recommendations for healthcare workers exposed to HIV.

The office also has other patient education material.

Getting Your Questions Answered

The HIV/AIDS Treatment Information Service can answer
individual questions, either by phone or by postal mail
address above, or by email to atis@.... It can
provide information from its database, but of course cannot
give medical advice.


***** Merck, Bristol-Myers Squibb Announce Major Price
Reductions for Poorest Countries: Major Access Progress but
Questions Remain

By John S. James

On March 7 Merck & Co. Inc. announced it would sell
Crixivan(R) (indinavir) in some poor countries for $600 per
patient per year, and Stochrin(R) (efavirenz, better known
in the U.S. as Sustiva(R)) for $500. The same price will be
available to governments, international agencies,
nonprofits, and private companies such as employers who
want to provide access to AIDS treatment to their
employees. The only condition placed on this program is
that the drugs must be used in the country and not
exported. Merck claims that it will not make a profit on
these sales to developing countries. It said it expects to
triple production of Crixivan to meet the new demand.

And on March 14 Bristol-Myers Squibb Company announced that
it was making its drugs ddI and d4T available "in every
country in Africa" at 15 cents per day for d4T and 85 cents
per day for ddI, which it said is below its cost, "under
its existing ACCESS partnership program with international
agencies, including UNAIDS, World Health Organization,
World Bank, UNICEF and U.N. Population Fund." (March 14
company press release).

Bristol-Myers Squibb also said that it would not let its
patents interfere with access to its AIDS drugs in Africa.
"The company will ensure that its patents do not prevent
inexpensive HIV/AIDS therapy in Africa. The patent for
Zerit, rights to which are owned by Yale University and
Bristol-Myers Squibb, will be made available at no cost to
treat AIDS in South Africa under an agreement the company
has recently concluded with Yale. The company has no other
patent rights in Africa which it will allow to prevent AIDS
therapy there," (March 14 press release). Outside of
Africa, "we will maintain our existing ACCESS pricing
program and address the subject on a country-by-country
basis." (About 70% of people with HIV or AIDS in the world
live in sub-Saharan Africa.)

Last May, Merck, Bristol-Myers Squibb, and three other
major pharmaceutical companies announced major price
reductions for developing countries, through the ACCESS
program with UNAIDS and other agencies. But that program
required country-by-country price negotiations between each
government and the companies. Only three countries
(Senegal, Rwanda, and Uganda) have completed these
negotiations, while about 30 others have expressed
interest; after 10 months, only about 2500 people are being
served. The new procedure should be much simpler in
practice, because of the transparent (public), uniform
price.

With prices currently announced for poor countries by other
pharmaceutical companies (which might be reduced in the
near future), prices to Africans for triple therapy
including either Crixivan or Stochrin (efavirenz) will
still be over $1000 per person per year. Two Indian generic
manufacturers (Cipla Ltd., and Hetero Drugs Ltd.) have now
offered a nevirapine-based triple combination for as low as
$350 per year or less. (Efavirenz and nevirapine are in the
same drug class, non-nucleoside reverse transcriptase
inhibitors; indinavir (Crixivan) is a protease inhibitor.
Indinavir is more difficult to manufacture than nevirapine;
we do not know about efavirenz.)

A March 7 WALL STREET JOURNAL report attributed Merck's and
other new pricing programs for poor countries to
"increasing concern by pharmaceuticals executives that
generic competitors are winning a public-relations battle
that could eventually undermine international patents --
their most precious asset."

In a March 19 op ed in THE NEW YORK TIMES, one of the
inventors of d4T, William Prusoff of the Yale University
School of Medicine, looked at the history that led to the
current developments. He supported the drug being either
cheap or free in sub-Saharan Africa, while also
acknowledging the contribution of Bristol-Myers Squibb,
which tested the d4T at its expense in more than 13,000
patients in the U.S. and Europe before it was able to get
any income from sales. He is amazed at how rapidly this
issue has moved recently.

Comment

These programs are clearly an important step forward, and
have generally been welcomed by agencies and advocates
trying to make treatment available. But clearly the $500 or
$600 price will require international assistance for
countries with income levels less than that and public
health expenditures sometimes less than $10 per person per
year -- in addition to money for training and other
infrastructure. Eventually millions of people will come in
for treatment, and it is not known how much funding will be
available to help provide it.

While we do not contest the companies' statements that it
will not profit on the sale of the drugs at these prices to
developing countries, we do note that any such calculation
is based on many accounting choices, which are not public.
Also note that with the huge profit margins on patented
pharmaceuticals in the industrialized world, patent holders
have little incentive to reduce production cost, since it
makes up so small a part of the price. So even accepting
the companies' statements fully, developing countries will
have to bear production costs set by rich-world economics
and not appropriate for them.

For the same reasons, there is not necessarily any conflict
between Bristol-Myers Squibb's statement that it will sell
ddI at a loss, and at least one generic company's quote for
ddI at a fraction of the price. Bristol has little
incentive to reduce production cost; generic companies have
great incentive. This is one of the reasons many activists
insist that generic competition must remain an available
option for providing these life-critical but expensive
drugs in poor countries.

We should think through the pros and cons of having an
individual-patient price (such as $600 per year for
Crixivan) for critical drugs for poor countries -- as
opposed to governments, international agencies, and others
contracting to pay pharmaceutical companies a flat price to
manufacture whatever amount of drug is needed for treatment
programs there. The problem with the individual-patient
price is that it could end up being charged as an out-of-
pocket expense to individual patients, who often have no
possibility of paying that much. On the other hand, the
problem with not having an individual price is loss of
flexibility; for example, the drugs might be restricted to
governments, some of which will not have distribution
programs ready even when some private employers want to
provide coverage. Perhaps using both would be best:
government and other public programs could receive the
drugs at a flat price regardless of quantity, yet
employers, insurance plans, and other private organizations
could buy the drugs for each patient they treat, if for
whatever reason the government did not provide them.

Both generics and reduced-price drugs from patent holders
will likely be used in the world's poorest countries.
Either way, the key to treatment access for most people
will be effective institution building to bring together
the necessary support -- including money, education and
other infrastructure, and rules that everyone can live
with.


***** MSF (Doctors Without Borders) Petition Against South
Africa Lawsuit, Deadline April 15

On March 19 we received the following announcement from
Médecins Sans Frontières (Doctors Without Borders), asking
for signatures on their online petition by April 15:

Médecins Sans Frontières (MSF) asks you to support South
Africa's efforts to make essential medicines more
accessible to its people by signing the global "Drop the
Case" petition at http://www.msf.org by April 15.

The petition calls on 39 pharmaceutical companies to drop
their lawsuit against the South African government. The
lawsuit is blocking the implementation of legislation that
aims to improve access to essential medicines by making
drugs more affordable.

With over four million already infected with HIV, South
Africa has the highest number of people living with
HIV/AIDS in the world. Very few can afford the treatment
that has extended and improved the lives of people in
richer countries. High prices are effectively denying
medicines to poor patients, condemning them to a premature
death.

MSF asks you to visit our website at http://www.msf.org to
sign the petition and demonstrate your support.

Please also forward this message to other concerned people
that you know. MSF is working with organizations around
the world to try to collect as many signatures as possible
by mid-April, when the case resumes in court. We will then
present the signatures to the 39 drug companies and to
governments.

*Thank you for your concern, Médecins Sans Frontières
Access to Essential Medicines Campaign*


***** Southern Africa Home Care: Conference Report

The first regional Southern African conference on home care
for persons with HIV took place March 5-8, 2001 in
Gabarone, Botswana. Internet reports, written by
correspondents from South Africa, Uganda, Botswana, and
Ghana are available at:

http://www.healthnet.org/programs/procaare-
hma/procaare.200103/threads.html#00006

Topics include nursing, psychosocial support, medical care,
living with HIV or AIDS, the role of the private sector,
and orphans.

The reporting was organized by Health & Development
Networks (http://www.hdnet.org), an organization "to
mobilize a more effective response to HIV/AIDS and other
health-and-development-related issues by improving
information, communication, and the quality of debate."
HDNET, which has offices in the Republic of Ireland and in
South Africa, has hosted AIDS email lists and other online
information for many years.


***** AmFAR Seeks Medical Writer/Editor in New York

The American Foundation for AIDS Research (AmFAR) is hiring
a medical editor for its treatment publications, including
the AmFAR HIV/AIDS Treatment Directory. This job is at the
organization's New York City location.

"The Editor will develop and edit style, accuracy and
comprehensiveness of treatment information for various
publications, and write reports and articles. Responsible
for collecting and verifying pre-clinical and clinical
treatment-related information from local, national and
international conferences, clinical research sites,
foundations, government, drug manufacturers and on-line
literature.

"Ideal candidate is science writer with at least a BS and 3
years experience in science/technical fields, and strong
general science background. Knowledge of statistical and
medical terminology, and history, pathogenesis and
epidemiology of HIV/AIDS required, with background in
reviewing and abstracting scientific literature desirable.

"Very competitive salary and benefit package. Send resume
and letter with salary requirements to: Susan Kennedy,
Director - Human Resources, 120 Wall Street, 13th Floor,
New York, NY 10005, (212) 806-1625, (212) 806-1606 fax,
susan.kennedy@....


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