AIDS TREATMENT NEWS Issue #364, May 11, 2001
phone 800-TREAT-1-2, or 215-546-3776

CONTENTS

** Tenofovir: Gilead Applies for Approval; Expanded Access
Liberalized
Patients who cannot construct a viable antiretroviral
regimen with approved drugs will now have easier access to
tenofovir, a drug that is currently experimental but may be
approved in about six months. Tenofovir is significant
because it appears to maintain its antiretroviral activity,
with resistant HIV developing relatively slowly.

** June 3 Demonstration in Washington to Mark 20th Year of
AIDS
Over 100 major AIDS organizations have called for a rally
in Washington D.C. to mark the 20th year since the
discovery of AIDS.

** International AIDS Candlelight Memorial, May 20
This year's Candlelight Memorial will occur in over 500
communities around the world.

** Updated Guidelines for Prevention of Mother-to-Infant
Transmission
Changes in the U.S. standard were announced May 4.

** Syringe Prescription Study Unexpected Bonus: Helping
Long-Time Users Quit Drugs
A study to see if syringe prescription by physicians could
reduce needle sharing also found an additional bonus --
helping some clients get off drugs, by getting them into
medical care and making possible conversations which
otherwise would not happen.

** TAG Seeks Policy Director
The New York-based Treatment Action Group is hiring a
policy director.

** South Africa Court Case -- Documents on the Web
Where to find background on the widely publicized case,
which ended April 19.

** AIDS TREATMENT NEWS Publication Schedule: No Issues
Dated April 2001

** Viral Load and T-Cell (CD4) Counts: Why They Matter
Simple-language flyer by writer Bruce Mirken answering
denialist arguments against standard blood tests. We
formatted this article for distribution to clients.


***** Tenofovir: Gilead Applies for Approval; Expanded
Access Liberalized

by Dave Gilden

Tenofovir, Gilead Sciences' candidate reverse transcriptase
inhibitor, could be approved in about six months. In an
unexpected move, the company announced May 1 that it had
filed a New Drug Application with the FDA. After approval,
tenofovir could be prescribed for any adult with HIV,
according to the company's proposed labeling. Gilead will
soon proceed with similar marketing applications in Europe.

Tenofovir, or PMPA, stops the infection of new cells by
halting the gene-building activity of HIV's reverse
transcriptase enzyme. The drug is similar to nucleoside
analogs such as ddI but requires less intracellular
processing to reach its active state. Tenofovir is
distinguished by its long intracellular half-life, which
allows once-a-day dosing. It also has a somewhat different
resistance profile than the standard nucleoside analogs, so
it may be active against many HIV isolates that have
mutated to resist the approved nucleoside analogs. In
trials so far, resistance to tenofovir has been slow to
develop -- although it has been found.

Tenofovir's safety profile is considerably improved over
adefovir, a closely related compound developed by Gilead.
Adefovir was rejected by the FDA because of severe kidney
toxicities coupled with modest efficacy.

Gilead's new drug may be helpful in a salvage regimen, but
it does not represent any dramatic breakthrough. In a 189-
person phase II treatment-intensification trial,(1)
tenofovir was added to volunteers' previous regimens at
doses of 0 mg (placebo), 75 mg, 150 mg or 300 mg per day.
The trial participants had a mean 4.6 years prior anti-HIV
therapy and a mean baseline viral load of 5,000. At study
entry, 94% of the enrollees also had HIV with mutations
conferring resistance to various nucleoside analogs,
principally AZT and 3TC. HIV in more than half of the
participants also had resistance to protease inhibitors.
The trial participants on 300 mg/day - the preferred dose -
recorded viral load reductions averaging about 0.6 log
(75%) through both weeks 24 and 48. The presence or absence
of AZT or 3TC resistance was not associated with a major
difference in the response. The modest, stable viral load
reduction was not accompanied by any appreciable change in
CD4 count, either.

Gilead scientists are reporting almost identical
preliminary results from a similar 552-person phase III
treatment-intensification trial. Both these trials make it
clear that tenofovir requires concomitant active
antiretrovirals from other drug classes to form a regimen
that can successfully suppress HIV. This is true in
treatment-naïve individuals, who appear to have a better
response to tenofovir, as it is in those with a history of
treatment failure. In its 600-person phase III trial for
those without prior treatment, Gilead is comparing
tenofovir directly to the nucleoside analog d4T, each
combined with the nucleoside analog 3TC and the NNRTI
efavirenz.

Expanded Access: Gilead Drops CD4, Viral Load Exclusions

Since last February, an expanded-access program has been
open to people whose advanced disease state and treatment
history mandate immediate use of new drugs to suppress
their HIV (see AIDS TREATMENT NEWS #360, February 23,
2001). Gilead always intended that this program would be
very small. It at first restricted entry to persons with
viral loads over 10,000 and CD4 counts under 100 - plus
documented treatment failure with at least two protease
inhibitors or one PI and one non-nucleoside reverse
transcriptase inhibitor (NNRTI). (Those with a CD4 count
between 100 and 200 could also apply if they had had an
AIDS-defining opportunistic infection within the last 90
days.)

Expanded-access enrollment has been even slower than
anticipated. Public dissatisfaction over the paltry
enrollment figures led Gilead to abandon its viral load and
CD4 count entry criteria. As to speeding up the enrollment
process, Debbie Fletcher of Gilead said in an interview,
"About 20% of the doctors have submitted incomplete
registration materials and had their applications returned.
The paper work can go back and forth and back and forth.
Our field representatives will follow up with the
physicians who don't finish filling out the forms."

One HIV specialist summed up his frustrating experience
with Gilead: "Paperwork did go back and forth. It took them
weeks to turn it around and tell you they needed something
more. Then you would send that, and they would come up with
something else."

The Coalition for Salvage Therapy has asked the company for
a full and regular accounting of the program's enrollment.
In a strongly worded letter, this national activist network
said that applicants to the program "are not only patients
with few or no remaining options for treatment, but also
patients whose disease has been allowed to progress to the
point where 'waiting for things to get sorted out' with the
program is simply not an option." The Coalition had long
pressured Gilead for a much broader expanded-access
distribution before finally settling for the present
restricted effort.

For the expanded-access program, Gilead advises doctors to
prescribe at least one new anti-HIV agent in addition to
tenofovir. Tenofovir naturally substitutes for other
nucleoside analogs, not for protease inhibitors or NNRTIs.
Some treatment activists have argued that Gilead should
abandon the requirement that enrollees have past failure
with PIs or NNRTIs. The program should be open to anyone
lacking new nucleoside analogs to create a viable treatment
combination.

This is the way tenofovir expanded access works in France,
where the drug is recommended for patients with nucleoside
analog intolerance or with nucleoside analog-resistant HIV,
as demonstrated by resistance assays. In the United
Kingdom, tenofovir is available to any patient who, in the
judgment of his or her doctor, could not otherwise
construct an effective anti-HIV regimen. Regulations in
both countries preclude strict entry criteria, including
CD4 count or viral load limits.

When tenofovir is approved, the issues around expanded
access will be largely academic. At least the program is
growing. Enrollment has picked up dramatically in the U.S.,
where about 150 people are now signed up. Also, Gilead has
asked Germany, Italy and Spain for permission to extend the
program beyond the U.S., UK and France. Further information
can be obtained from Gilead at 1-800-Gilead-5 in the US and
33-1-44-90-34-46 in Europe.

References

1. Miller MD et al. Baseline and Final Phenotypic Analysis
of HIV-1 from Patients Adding Tenofovir Disoproxil Fumarate
(TDF) Therapy to Background ART. 8th Conference on
Retroviruses and Opportunistic Infections. February 4-8,
2001. Poster 441.


***** June 3 Demonstration in Washington to Mark 20th Year
of AIDS

On June 3 over 100 organizations, including the NAMES
Project AIDS Memorial Quilt, National Minority AIDS
Council, National Association of People with AIDS, Project
Inform, Gay Men's Health Crisis, and many ACT UP chapters
will mark the 20th year of the AIDS crisis with a march on
the Pharmaceutical Research and Manufacturers Association,
Congress, and the White House. There will be a reading of
all 80,000 names within the AIDS Memorial Quilt, although
the Quilt itself will not be displayed.

The organizers are calling for youth and children to lead
the march. Worldwide, over 4,000,000 children under 15 have
been killed by AIDS, and over 13,000,000 children have been
orphaned.

For more information, see
http://www.AIDSaction20.org Marchers are urged to make
hotel arrangements soon. The march will begin at noon on
June 3 in Washington D.C.


***** International AIDS Candlelight Memorial, May 20

On May 20 the annual International AIDS Candlelight
Memorial is taking place at more than 500 communities
around the world. More information, including local
contacts, is at
http://www.candlelightmemorial.org


***** Updated Guidelines for Prevention of Mother-to-Infant
Transmission

On May 4 the U.S. Public Health Service released an updated
version of the official guidelines for use of
antiretrovirals to reduce perinatal HIV transmission. The
following sections have been changed:

* "Antiretroviral Clinical Scenarios" (beginning on page
17);

* "Recommendations for Monitoring of Women and Their
Infants" (beginning on page 39); and

* "Clinical Research Needs" (beginning on page 41).

You can obtain a copy of the guidelines without charge in
any of three ways:

(1) http://hivatis.org/trtgdlns.html , the Web site of the
HIV/AIDS Treatment Information Service;

(2) by calling 1-800-448-0440 or 301-519-0459, Monday
through Friday 9-5 Eastern Time (TTY 888-480-3739); or

(3) by mailing a request to HIV/AIDS Treatment Information
Service, P.O. Box 6303, Rockville, MD 20849-6903. It may
take 7-10 days plus shipping time to receive the document.

Ask for the Perinatal Guidelines. (The full official title
is "Public Health Service Task Force Recommendations for
the Use of Antiretroviral Drugs in Pregnant HIV-1 Infected
Women for Maternal Health and Interventions to Reduce
Perinatal HIV-1 Transmission in the United States."

Note: For information in English, Spanish, or Portuguese
about federally approved treatment for HIV and AIDS, you
can contact health information specialists at the HIV/AIDS
Treatment Information Service, Monday through Friday 9-5 at
the phone numbers, email, or mailing address above.


***** Syringe Prescription Study Unexpected Bonus: Helping
Long-Time Users Quit Drugs

by John S. James

A pilot study in Rhode Island, allowing physicians to
prescribe syringes in order to reduce that state's
exceptionally high rate of HIV infection among injection
drug users, not only reduced needle sharing as hoped, but
also helped some patients get into drug treatment programs
and quit their drug abuse entirely. These people had been
injecting drugs for a median of 10 years. A description of
the project appeared in May issue of the American Journal
of Public Health(1).

On May 4 we spoke to principal investigator Josiah D. Rich,
M.D., M.P.H., an infectious-disease specialist. He
explained that until recently Rhode Island had one of the
harshest syringe laws in the nation. Possession of each
syringe was a felony punishable by up to five years in
prison, and the average sentence for possession of syringes
alone was 11 months. As a result drug users often did not
carry syringes but re-used those available where they
bought their drugs, and Rhode Island is one of only four
states where more than 50% of AIDS cases are due to
injecting drugs. And the state spent was spending over a
million of dollars a year arresting, trying, and
imprisoning people for syringes.

A coalition of medical organizations and others worked to
change the law, and they won a partial victory in 1998;
possession of syringes was reduced to a misdemeanor, but
they remained illegal (until 2000) and drug users had
difficulty getting sterile syringes. Lobbyists said it
would take at least two years to change the law again.
Evaluation of the law revealed that doctors could prescribe
syringes if approved by the state Department of Health; a
drug user could have a prescription and buy and possess
syringes legally, like a diabetic. So a study, the Rhode
Island Blood Borne Pathogen Harm Reduction Program, was
designed to see if prescribing syringes would help to
reduce sharing and HIV transmission.

The program began when the director of the Rhode Island
Department of Health, with the support of many medical
organizations, wrote to all licensed physicians in the
state, inviting them to join the program under certain
conditions. At this time the program employs four
physicians at two locations in Providence, Rhode Island and
has enrolled 350 drug users and prescribed 50,000 syringes.
The published report is preliminary, as data are still
coming in, but it appears that needle re-use has dropped
dramatically and that the syringes are being disposed of
properly.

The surprise for researchers was the great interest among
these hard-core users not only in obtaining the syringes,
but also in getting into drug treatment. There was an
overwhelming response, despite the fact that those who
approached the program were very high risk, with most of
them having injected illegal drugs for at least 10 years.
Half were homeless. A large majority had hepatitis C, and
many had hepatitis B as well.

"What is most remarkable is that these long-time users were
very interested in drug treatment -- half said did want
treatment to help them stop using drugs. We do not ask
immediately. We take a medical history, do a physical, and
discuss the findings. We tell them that their behavior is
very dangerous because of the risk of infectious diseases,
overdose, and other lifestyle problems. I recommend, as
their doctor, that we work together to try to get them to
stop.

"But if they are not able or willing to stop at this time,
I teach them sterile technique that doctors use for
injection -- including the use of a sterile syringe.

"They come to us to ask for syringes. So they have to admit
that they inject drugs, and here there are no negative
consequences to admitting that they are injecting drugs.
Who else can have this discussion with them? Usually the
people they talk to about their drug use -- their dealer,
pimp, or peers -- have a vested interest in them continuing
to use drugs.

"This program has a unique window into peoples' lives. We
can ask them, if you decide to stop, what would you do?
Would you go to detox? What was your experience in detox
last time? What if there are no beds now -- would you just
give up?

"It is most rewarding when patients come in and say they do
not need syringes -- that they have looked at their lives
and stopped their drug use because they are tired of what
it is doing to them. We see that as doctors, we can really
help these people."

This is the first time that a physician syringe
prescription program has ever been tried (although a few
physicians have prescribed syringes to individual
patients). The May 2001 article(1) includes recommendations
for those who want to try such a program elsewhere --
starting with knowing the local legal situation.(2)

From the article:(1)

"Because of the illicit nature of drug use, a tremendous
amount of mistrust and fear often leads to poor interaction
with the medical establishment. Prescription of syringes by
a physician can serve as a tool for reaching out to a high-
risk and often out-of-treatment population of drug users.
It is a way for the health care community to tap into drug-
using networks and bring those populations into a medical
care system..."

"That the physician-patient interaction is based on the
acknowledgement of injecting behaviors engenders trust and
seems to open the door for discussion of a whole host of
injecting-related activities, including commercial sex,
participation in the underground economy, violence, and
abuse. The participants seem to be open and honest about
their drug use.

They understand that physicians are trying to help them in
a non-judgmental way and are quite appreciative of the
efforts. Participants are extremely willing to participate
in health care including hepatitis B vaccination; testing
for hepatitis, HIV, and other sexually transmitted
diseases; and followup."

This study was funded in part by the American Foundation
for AIDS Research (AmFAR).

References

1. Rich JD, Macalino GE, McKenzie M, Taylor LE, and Burris
S. Syringe prescription to prevent HIV infection in Rhode
Island: A case study. AMERICAN JOURNAL OF PUBLIC HEALTH.
May 2001; volume 91, number 5, pages 1-2.

2. Burris S, Lurie P, Abrahamson D, and Rich JD. Physician
prescribing of sterile injection equipment to prevent HIV
infection: Time for action. ANNALS OF INTERNAL MEDICINE.
August 1, 2000; volume 133, number 3, pages 218-226.


***** TAG Seeks Policy Director

The Treatment Action Group (TAG), a New York-based
nonprofit organization focusing on AIDS research and
treatment policy, is hiring a policy director. From the
announcement:

"The Policy Director will have a broad-based background
incorporating an understanding of science, government, and
policy, and ideally would have experience managing highly-
qualified people working in policy roles. The Policy
Director will be the key staff person responsible for
setting and implementing and coordinating the overall
policy agenda for TAG -- in conjunction with the executive
director -- and thus for oversight, facilitation, and
supervision of the policy and program work of the
agency..."

For years TAG has been one of the most important AIDS
treatment advocacy organization. It has been called a
"think tank without walls," as it provides computer and
communication equipment to staff who work from home
offices. It also has a small central office. Staff travel
frequently to research and treatment meetings and
conferences. Its Web site is
http://www.treatmentactiongroup.org

"Interested candidates should send a letter expressing
their qualifications and interest in the position with a
resume/CV and three references with contact information by
31 May 2001 to: Policy Director Search, c/o Regina Gillis,
Treatment Action Group, 350 Seventh Ave., Suite 1603, New
York, NY 10001, phone 212-971-9022, fax 212-971-9019, email
tagnyc@...


***** South Africa Court Case -- Documents on the Web

Documents in the lawsuit by 39 pharmaceutical companies
against Nelson Mandela and the government of South Africa,
dropped April 19 after becoming a public-relations disaster
for the companies, are available on the TAC (Treatment
Action Campaign) Web site, http://www.tac.org.za

From the other side, the International Association of
Pharmaceutical Manufacturers Associations has the one-page
"Joint Statement of Understanding between the Republic of
South Africa and the Applicants, and a press release, at
its Web site, http://www.ifpma.org/ (select News).

In our view the real significance of this case was not so
much the legal issues, but rather in showing that world
public opinion will no longer allow lifesaving medicines to
be priced out of reach of millions of people in poor
countries in order to avoid the risk of disturbing
lucrative markets in rich countries. Three years ago when
the case was filed, very few people were aware of this
issue. Now millions are aware, and millions are demanding
access to treatment. Industry is welcome to help in
developing systems that work, rules everyone can live with.
When industry fails to provide viable leadership, the work
will be done without them.


***** AIDS TREATMENT NEWS Publication Schedule: No Issues
Dated April 2001

Because we have been more than a month behind our twice-
monthly publication schedule, we will not publish any
issues dated April 2001. All subscriptions will be extended
a month to compensate, so subscribers will receive the same
number of issues.

Our previous issue, #363, was dated March 30. This issue,
#364, is dated May 11.


***** Viral Load and T-Cell (CD4) Counts: Why They Really
Matter

[Note: This article is part of our series answering the
AIDS denialists, who say that HIV does not cause AIDS and
who often urge patients to reject medical advice. Writer
Bruce Mirken prepared this simple-language version to help
agencies prepare materials for their clients.]

If you are being treated for HIV or AIDS, your doctor uses
a number of blood tests to check how you're doing. One of
the most important tests measures VIRAL LOAD, the amount of
HIV in your blood. Another very important test counts your
CD4 CELLS, sometimes called T-CELLS. CD4 cells are a key
part of your body's disease-fighting defenses, called the
immune system.

But some people claim that HIV doesn't really cause AIDS.
These people, known as "AIDS deniers," "denialists" or
"AIDS dissidents," also say that viral load and CD4 tests
are meaningless. They claim these tests don't really tell
anything about your health, and that they might even hurt
you by frightening you for no reason.

What Do Viral Load and CD4 Tests Really Tell Us?

What are CD4 Cells?

CD4 cells help to organize your body's defenses against
disease. Doctors can take a sample of your blood and count
the number of CD4 cells. Healthy adults and teenagers
usually have a CD4 count of at least 800 cells per CUBIC
MILLIMETER of blood (a cubic millimeter is a very small
amount, roughly one small drop).

What does HIV do to CD4 counts?

HIV attacks CD4 cells, and as time goes by people with HIV
often see their CD4 counts drop. The lower your CD4 count,
the greater your chances of getting a number of very
serious diseases. When your CD4 count is below 200, the
risk of illness becomes severe.

I've heard that you can have a low CD4 count and still be
healthy. Is that true?

While there have been a few medical reports of people who
seemed healthy even though they had very low CD4 counts,
these cases are rare. Research overwhelmingly shows that
people with low CD4 counts are much more likely to get sick
than people who have a normal amount of CD4 cells.

The AIDS denialists who claim that CD4 counts are
meaningless often point to a study of AIDS patients called
the Concorde study, in which people who had a small
increase in CD4 counts did not live longer than those whose
CD4 counts stayed the same. But that study was done nearly
10 years ago, before modern combination therapy, and the
CD4 increases were very small. Newer studies with more
potent treatments show that a big boost in CD4 cells almost
always lowers the risk of getting seriously ill.

For example, the deadly pneumonia called PCP occurs much
more often in people with very low CD4 counts. In one
study with over 1,000 patients, almost everyone who got PCP
had a CD4 count below 200. Study after study has shown the
same thing: The lower your CD4 count, the greater your
chance of getting PCP or other serious infections.

The AIDS denialists leave out these important facts.

Why are viral load tests used?

CD4 counts give you and your doctor a good idea of how much
damage HIV has done to your immune system. But you also
need to know how fast that damage is happening. Viral load
tests, which tell the doctor how much HIV is in your blood,
are a very important clue to how quickly HIV is doing harm.

These tests go by several different names, like PCR
(polymerase chain reaction) or bDNA (branched DNA), but
they all work roughly the same way. They count HIV's
genetic material--the building blocks of the virus

What does viral load tell us?

People with a high viral load are much more likely to get
sick or die of AIDS than people with a low viral load.

The AIDS denialists sometimes suggest reasons why these
tests might give a wrong answer. They point to a few old
reports, from when viral load tests were new and still
experimental, as evidence that they don't work. But there
is a huge pile of newer evidence showing that viral load
tests work extremely well. Many studies have shown that
people with high viral loads are more likely to get sick or
die from AIDS-related illnesses than people whose viral
load is lower.

For example, one very important study has followed
thousands of gay men since 1984. A few years ago
researchers did viral load tests on the very earliest blood
samples from that study and then looked at how many of
those patients were still alive. The men with the highest
viral loads were 77 times more likely to have died of AIDS
than those with the lowest viral loads. Other studies in
the U.S. and Europe have shown the same thing: A higher
viral load almost always means a higher risk of sickness
and death.

What happens when treatment reduces my viral load?

Studies have shown that when treatment reduces your viral
load, it also reduces your chance of getting an AIDS-
related infection or dying. Recently, a group of expert
scientists reviewed 18 studies of anti-HIV drugs, which
involved over 5,000 patients. Over and over again they
found the same thing: The more viral load was reduced, the
healthier the patients stayed.

The Bottom Line

No medical test is perfect, and mistakes or
misunderstandings sometimes happen. You should always go
over your test results carefully with your doctor to make
sure you understand them.

But the people who claim that viral load and CD4 tests are
useless are not telling the truth. These tests give you
and your doctor important information that can help you
make the best treatment choices.


***** AIDS TREATMENT NEWS

Published twice monthly

Subscription and Editorial Office:
1233 Locust St., 5th floor
Philadelphia, PA 19107
phone 800/TREAT-1-2 toll-free, or 215-546-3776
fax 215-985-4952 (email is preferred)
email: aidsnews@...
useful AIDS links: http://www.aidsnews.org

Editor and Publisher: John S. James
Associate Editor: Tadd T. Tobias

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.

AIDS TREATMENT NEWS is published 24 times per year, on the
first and third Friday of every month, and print copies are
sent by first class mail. Email is available (see below).
Back issues are available at http://www.aidsnews.org

To subscribe, you can call 800-TREAT-1-2 or 415-255-0588:
* Businesses, Institutions, Professionals: $325/year. Early
email available (see below).
* Nonprofit organizations: $150/year.
* Individuals: $140/year, or $80 for six months. If you
cannot afford a subscription, please write or call about
our sliding scale.
* Outside North, Central, or South America, add airmail
postage: $20/year, $10 for six months.
* Bulk rates and multiple discount subscriptions are
available; contact our office for details.
* Payment can be by check, VISA, Mastercard, American
Express, bank draft, purchase order, international postal
money order, or travelers checks.

Early email: Business, nonprofit and full-rate individual
subscribers can receive an early copy by email, before the
issue is printed--in addition to their regular copy, at no
extra charge. It's OK to direct the email copy to someone
else. Call our office to add email to your subscription.

Free email: Free delivery for individuals (delayed one week).
To subscribe, send a blank email to:
aidsnews-subscribe@yahoogroups.com

ISSN # 1052-4207

Copyright 2001 by John S. James. Permission granted for
noncommercial reproduction, provided that our address and
phone number are included if more than short quotations are
used.

--
John S. James
AIDS Treatment News
http://www.aidsnews.org