AIDS TREATMENT NEWS Issue #373, October 26, 2001
phone 800-TREAT-1-2, or 215-545-3776

CONTENTS

** Tenofovir Approved: Broad Indication
The FDA approved this important new anti-HIV drug on
October 26, without restricting it to heavily pretreated
patients.

** T-20 Small Program, CD4 < 50, Will Enroll November 27 at
3:00 P.M.
A small safety study for patients with a CD4 count under 50
and who cannot construct a viable antiviral regimen with
approved drugs will open for registration on November 27.
Only the first 56 physicians who call in, and have exactly
three eligible patients each, will be accepted.

** Treatment News from Recent Conferences: Finding Web
Reports
Several important AIDS treatment conferences are reported
extensively on different Web sites. Here is a way to
quickly find what is new in particular areas of treatment
and research.

** Anthrax, Bioterrorism Fears Stimulate Immune, Other
Research
The need for defense against biological warfare is pushing
the development of new drugs that could fight many
diseases. Many of these work by changing the body's immune
response; others use different mechanisms. Some of the
approaches now being studied are related to certain
traditional or alternative treatments.

** Africa: Funding Sought for Epidemic Control
Over 75 members of Congress have called for new funding to
fight epidemics worldwide, especially in developing
countries.

** World AIDS Day Web Page
Where to find information about World AIDS Day, December 1.


***** Tenofovir Approved: Broad Indication

by John S. James

On October 26 the FDA approved Viread (tm) -- generic name
tenofovir disoproxil fumarate, or tenofovir DF. The
approval was expected; less expected was the broad
indication, which both the company and treatment activists
wanted, but which some of the advisory committee had
questioned (see "Tenofovir: FDA Hearing on Important New
Antiretroviral," AIDS TREATMENT NEWS #372, October 19,
2001). From the package insert:

"INDICATIONS AND USAGE

"VIREAD is indicated in combination with other
antiretroviral agents for the treatment of HIV-1 infection.
This indication is based on analyses of plasma HIV-1 RNA
levels and CD4 cell counts in a controlled study of VIREAD
of 24 weeks duration and in a controlled, dose ranging
study of VIREAD of 48 weeks duration. Both studies were
conducted in treatment-experienced adults with evidence of
HIV-1 viral replication despite ongoing antiretroviral
therapy. Studies in antiretroviral naive patients are
ongoing; consequently, the risk-benefit ratio for this
population has yet to be determined.

"Additional important information regarding the use of
VIREAD for the treatment of HIV infection:

"* There are no study results demonstrating the effect of
VIREAD on clinical progression of HIV.

"* The use of VIREAD should be considered for treating
adult patients with HIV strains that are expected to be
susceptible to tenofovir as assessed by laboratory testing
or treatment history."

A patient-oriented description of the drug appears at:
http://www.aidsmeds.com/drugs/tenofovir.htm

The Medscape drug-interaction calculator, recently updated
to include tenofovir, is at:
http://hiv.medscape.com/Medscape/HIV/DrugInteractions/index.cfm

An FDA Talk Paper is at:
http://www.fda.gov/bbs/topics/ANSWERS/2001/ANS01111.html

And the complete package insert can be found on the Gilead
site at:
http://www.gilead.com/prod_pdf/viread_pi.pdf


***** T-20 Small Program, CD4 < 50, Will Enroll

November 27 at 3:00 P.M.

by John S. James

A small and difficult T-20 expanded-access program will
begin receiving phone calls from U.S. physicians on
November 27 at 3:00 p.m. Eastern time. The first 56
eligible physicians will be accepted. Each physician must
have exactly 3 patients who qualify for this program when
they call. The 168 patients accepted will be eligible to
receive T-20 when the program starts -- in the first
quarter of 2002, depending on drug supply.

T-20 is the first member of a new class of anti-HIV drugs
called fusion inhibitors, which block the entry of HIV into
cells. Because it works by a different mechanism than any
approved drug, virus resistant to the approved drugs is not
expected to be resistant to T-20. However, T-20 resistance
can develop when the drug is used, as with the other
antiretrovirals.

Patients must have a CD4 count under 50, a viral load over
10,000, and be at least 16 years old. Physicians are asked
to give preference to patients "who have had an AIDS
defining opportunistic infection, neoplasm or condition AND
CD4 lymphocyte count <50 cells/mm(3), both while on HAART
within the last 90 days."

T-20 is being developed jointly by Roche Pharmaceuticals
and Trimeris, Inc., and is currently in phase III clinical
trials. This new program is called Protocol T20-305, "Open
Label Safety Study of T-20 in Patients with Advanced HIV
Disease who are Unable to Construct a Viable Antiviral
Regimen."

Physicians interested in this program should make sure that
they have a November 2 Dear Doctor letter from Trimeris and
Roche, which was sent to 2,000 AIDS-treating physicians on
November 2; currently it is on the Web at
http://www.hivandhepatitis.com/recent/resistance/110701a2.html
Also, a physician or patient with questions about T-20 can
call Professional Product Information at Roche, 1-800-526-
6367, 8:00 a.m. to 6:30 p.m. Eastern time Monday through
Friday, either before or after November 27. (Note: This is NOT
the number to call starting November 27 at 3:00 P.M.; see the
physician letter for complete information.)


***** Treatment News from Recent Conferences: Finding Web
Reports

by John S. James

Much treatment information came out at several conferences
in October and early November. It did not get major press
attention because there was no big headline story or single
coherent message. Unless you know someone who was there,
the best way to learn about these conferences shortly after
they happen is through Web reports by researchers,
physicians, or other experts. While few will read all this
material, patients and medical professionals can scan to
find information about problems they are having, treatments
they are using, or relevant leads.

You can scan the lists of major topics, below, to decide
what you want to see, then go to the Web sites to read the
selected summaries. Note that these reports are written
mainly for medical professionals, and some are more
difficult than others.

These conference Web reports provide quick, accessible
treatment education updates in areas you choose. This
article lists major topics reported (as of mid November
2001, when we went to press).

Recent Conferences

* IDSA 2001 (annual conference of the Infectious Diseases
Society of America), October 25-28 in San Francisco;

* The 3rd International Workshop on Adverse Drug Reactions
and Lipodystrophy in HIV, October 23-26 in Athens, Greece;

* The 8th European Conference on Clinical Aspects and
Treatment of HIV Infection (ECCATH), October 28-31 in
Athens, Greece (by the European AIDS Clinical Society);

And for reports on liver diseases,

* 66th Annual Scientific Meeting of the American College of
Gastroenterology, October 19-24, Las Vegas;

* AASLD (American Association for the Study of Liver
Diseases), will be held November 9-13, Dallas.

Web Sites with Conference Coverage

The following four sites have extensive reporting on these
conferences (though only The Body covered all five of
them).

Note the more specific Web addresses for some of the
conference coverage, further below. But if one of these
addresses does not work (perhaps because the site has been
reorganized), use the address here to get to the home page,
and then look for the conference coverage on the site. Some
sites take down their conference reports after one year.

* The Body, http://www.thebody.com, has the most extensive
conference coverage.

* HIV and Hepatitis.com,

http://www.hivandhepatitis.com has perhaps the most
extensive coverage of AIDS and hepatitis treatment news on
the Web.

* Medscape, http://www.medscape.com has many excellent
medical resources. (You need to register and choose a
password to use this site, but the registration is free.)

* NATAP (National AIDS Treatment Advocacy Project),
http://www.natap.org has valuable information, though some
of it has been technical and hard to read.

While these Web sites are credible, nothing is perfect.
These rapid Web reports, often online within days of a
meeting, sometimes within a day, do not always leave time
for thorough fact checking. And the pervasive "spin"
throughout the entire U.S. medical field, especially
pharmaceuticals, makes all treatment reporting difficult.
The trials conducted and results published reflect complex,
often secret negotiations between corporate, professional,
regulatory, organizational, personal and other interests.
There is no way to cover a field as complex as AIDS and
even be aware of all of the important spin.

Approved HIV Drug Names

We use generic drug names in this article -- or the more
familiar abbreviations AZT (generic name zidovudine), ddI
(didanosine), d4T (stavudine), and 3TC (lamivudine).
Generic names are usually but not always used on the sites.
For those more familiar with the brand name, here is a
table of the brand names and generic names of the anti-HIV
drugs currently approved in the U.S. Since all
antiretrovirals are patented in this country, there is only
one brand name here for each generic (except for
saquinavir, which has an earlier, weaker formulation named
Invirase).

Agenerase amprenavir
Combivir [AZT+3TC]
Crixivan indinavir
Epivir lamivudine (3TC)
Fortovase saquinavir
Hivid zalcitabine (ddC)
Kaletra lopinavir/ritonavir
Norvir ritonavir
Rescriptor delavirdine
Retrovir zidovudine (AZT)
Sustiva efavirenz
Trizivir [abacavir+AZT+3TC]
Videx didanosine (ddI)
Viracept nelfinavir
Viramune nevirapine
Viread tenofovir DF
Zerit stavudine (d4T)
Ziagen abacavir

Major Topics Covered

Here are some of the most important topics on each site, as
of November 14. New reports may still be added. If we have
missed other sites that should be included, please let us
know.

Also note that the same research is often presented at more
than one conference. So the same Web site can have
different writeups on the same research.

We wrote the title lines below to give a less technical
view of the contents of each summary. You can usually spot
the corresponding writeup by following the link provided to
reach a table of contents for that conference Web report.
Many of the summaries are short, a page or less; a few are
considerably longer.


** IDSA (39th Annual Meeting of the Infectious Diseases
Society of America), October 25-28, San Francisco

The Body
http://www.thebody.com/confs/idsa2001/idsa2001.html
(click "Conference Summaries")

* Can short-term changes in viral load predict long-term
response?

* Transmission of drug-resistant HIV;

* Lopinavir/ritonavir in heavily pretreated patients;

* Starting therapy at a T-cell count of 350;

* Simplifying protease-inhibitor treatment by switching to
abacavir;

* Nevirapine and liver toxicity in HIV patients with
hepatitis C;

* Nevirapine vs. protease inhibitors -- long-term cohort
study;

* Using amprenavir after nelfinavir use;

* Amprenavir+abacavir+3TC, 48-week data;

* Abacavir+efavirenz+AZT+3TC, preliminary 48-week results;

* Four-drug study, efavirenz+abacavir+AZT+3TC;

* Hepatitis G co-infection and HIV treatment;

* EPO (erythropoietin, Epoetin Alfa) in anemic HIV
patients;

* Prior antiretroviral therapy and genotype testing;

* How well can patients predict their T-cell and viral load
test results?

* Cutting-Edge Issues in HIV Medicine (symposium)

- Challenges of Antiretroviral Therapy in the Developing
World;

- Future Horizons in Antiretroviral Drugs;

- Structured Treatment Interruption: Panacea or Pandora?

- HIV and HCV Co-Infection -- Current Status and Future
Directions.

HIVandHepatitis.com
http://www.hivandhepatitis.com/2001conf/39idsa/main.html

"Report on Salvage Therapy from the 39th Annual Meeting of
the IDSA," by Daniel R. Kuritzkes, M.D. This essay looks at
real-world experience in very heavily pretreated patients
with: lopinavir/ritonavir (Kaletra); indinavir+ritonavir;
delavirdine strategy to boost protease inhibitor levels;
and amprenavir use after nelfinavir.

Medscape
(Note: The following URL is on to lines.)
http://hiv.medscape.com/Home/Topics/AIDS/directories/
dir-AIDS.ConfSummaries.html
(then select 39th Annual Meeting of the Infectious Diseases
Society of America)

These are the HIV-related titles now on the site:

* Antiretroviral Agents and Response to Therapy

* Optimizing Long-term HIV Treatment Strategies Through a
Greater Understanding of Disease Pathogenesis

* Metabolic Complications and Adverse Drug Reactions in HIV

* Update: Incidence, Diagnosis, and Clinical Manifestations
of HIV-Related Opportunistic Infections

* PI vs. Boosted PI vs. Efavirenz: And the Winner (Again)
Is?

* Switching from a Protease Inhibitor: The Answers Are
Known, It's Time to Move On

* Four-Drug HAART Regimen in Patients with Advanced HIV
Disease

* HIV Evolution Limited by Successful HAART

* A New and Simple Way to Diagnose Pneumocystis carinii
Pneumonia

* Evidence for Increased Risk of Heart Disease in Treated
HIV Infection

* Myocardial Infarction: A Consequence of HIV Disease,
Treatment, or Both?

* Has HAART Really Improved Mortality in Patients with
Advanced HIV Disease?

* Rates of Most HIV-Related Diseases No Longer Falling

Note: Bioterrorism, and other infectious diseases, have
separate sections in this Web report from the IDSA
conference.


** 8th European Conference on Clinical Aspects and
Treatment of HIV-Infection

The Body
http://thebody.com/confs/eccat2001/eccat2001.html (click
"Conference Summaries")

* TMC-125, experimental NNRTI, produced 2-log HIV reduction
in volunteers; [Note: "NNRTI" is an abbreviation for "non-
nucleoside reverse transcriptase inhibitor," a class of
anti-HIV drug. Two drugs in this class are currently
approved, nevirapine and efavirenz.]

* Indinavir/ritonavir vs. saquinavir/ritonavir;

* NNRTI use and lipodystrophy study;

* Nevirapine and HDL cholesterol ("good cholesterol");

* Tipranavir, a new kind of protease inhibitor;

* Tenofovir intensification study;

* Cardiovascular risk factors, association with
antiretroviral therapy;

* First-line treatment choice and lipid metabolism;

* Switching from protease inhibitors to NNRTIs;

* Tenofovir, antiretroviral activity regardless of baseline
demographics, CD4, viral load;

* Long-term followup of switching from protease inhibitors
to NNRTIs with undetectable viral load;

* Lack of drug interaction between tenofovir and several
other anti-HIV drugs;

* Once-daily treatment with experimental drug emtricitabine
(FTC, brand name Coviracil), ddI, and efavirenz, 2-year
followup;

* Atazanavir (experimental protease inhibitor) 48-week data
on lack of lipid elevation;

* Nevirapine, ddI, and d4T long-term followup;

* Minor interaction between efavirenz and
saquinavir/ritonavir.

HIV and Hepatitis.com
http://www.hivandhepatitis.com/2001conf/8thclinical/main.html

* Atazanavir at 48 weeks;

* Saquinavir/ritonavir new dosage regimen;

* Lopinavir (Kaletra) 3-year data in treatment naive
patients;

* Switching from protease inhibitor(s) to NNRTI;

* Once daily d4t;

* T-20 (experimental fusion inhibitor, a new class of
antiretroviral);

* Saquinavir and efavirenz interaction corrected with
ritonavir;

* Efavirenz, ddI, and FTC (Coviracil) combination, 96-week
study;

* Nevirapine and lipid profile improvement;

* Once daily vs. twice daily nevirapine;

* No important drug interaction between tenofovir and
indinavir, lopinavir, 3TC, or efavirenz;

* TMC 125, experimental NNRTI;

* Efavirenz vs. nevirapine in treatment-naive patients;

* Switching from a protease inhibitor to efavirenz.

NATAP
http://www.natap.org/ -- select 'Conference Reports' (on
left), then '2001' (if necessary), then select the
conference by name

* Atazanavir vs. nelfinavir;

* T-20 late phase II results;

* Extended-release d4T;

* Tibotec/Virco presentations, including TMC 125 (an
NNRTI), and a method for predicting response to protease
inhibitors;

* T-20 data in adults and children, and T-1249 data in
adults. (T-1249 is a "second generation" T-20.)

* Indinavir/ritonavir vs. saquinavir/ritonavir, both twice
daily;

* Hepatitic C and B.


** 3rd International Workshop on Adverse Drug Reactions and
Lipodystrophy in HIV

The Body
http://www.thebody.com/confs/adrl2001/adrl2001.html
(click "Conference Summaries")

* Mitochondrial function may not be causing lactate
elevation;

* Increased lipolysis (fat destruction) in HIV, with or
without fat redistribution;

* Inhibiting lipolysis improves insulin sensitivity;

* Lactate risk factors in antiretroviral therapy;

* More tumor necrosis factor released from skin fat in HIV
patients with lipodystrophy;

* Lab studies comparing indinavir, nelfinavir, and
amprenavir effects on fat cells -- and protection by
rosiglitazone;

* Lipodystrophy and metabolic disorders 48 weeks after
switching from protease inhibitors to Trizivir, vs. not
switching;

* Prospective study of lipid elevation with two
antiretroviral regimens.

HIV and Hepatitis.com
http://www.hivandhepatitis.com/2001conf/3rdlipo/main.html

In an excellent but quite technical summary of the
lipodystrophy workshop, ten papers by leading experts
describe what happened in various areas:

By Andrew Carr, M.D.: Mitochondrial Toxicity and Lactic
Acidemia; Liver Disease; Hypersensitivity; and Thyroid
Disease.

By Graeme Moyle M.D., M.B.B.S.: Insulin Resistance;
Adipocytes (fat cells); Clinical Data; Switch Studies;
Cardiovascular Disease; and Clinical Risk.

NATAP
http://www.natap.org/, select 'Conference Reports' (on
left), and then '2001'

* Overview;

* Lipodystrophy;

* Amprenavir;

* List of conference highlights;

* Abacavir;

* Mitochondrial toxicity and lipodystrophy;

* Nevirapine;

* Thyroid abnormalities;

* Lactic acidosis and mitochondrial toxicity;

* Potential therapy for lipodystrophy;

* Heart disease risk;

* Abnormalities of glucose metabolism.

Liver Disease Conferences Coverage


** The following conferences are most relevant for coverage
of hepatitis or other liver-related illness.


** 66th Annual Scientific Meeting of the American College
of Gastroenterology, October 19-24, Las Vegas

The Body
http://thebody.com/confs/gastroenterology/gastroenterology.html
(click "Conference Summaries")

* Hepatitis C;

* Liver disease in AIDS;

* New treatments for hepatitis C;

* PEG-interferons: When to use them;

* PEG-interferons: How to use them;

* Lamivudine (3TC) for hepatitis C: When to start, when to
stop.


** AASLD (American Association for the Study of Liver
Diseases), November 9-13, Dallas

The Body
http://www.thebody.com/confs/aasld2001/aasld2001.html

Check the site; coverage incomplete as we went to press.

HIV and Hepatitis.com
http://www.hivandhepatitis.com/2001conf/52aasld/main.html

Check the site; coverage just began as we went to press.

NATAP, http://www.natap.org/, select 'Conference Reports'
(on left), then '2001'

Check the site; coverage just began as we went to press.


***** Anthrax, Bioterrorism Fears Stimulate Immune, Other
Research

Comment by John S. James

A November 7 press report ("All-Purpose Drugs Are Being
Tested," by Jeff Donn, The Associated Press) surveyed some
of the work being done on finding drugs to treat many
diseases -- the opposite of the traditional "magic bullet"
approach of targeting only one particular bacterium or
virus. Many of these "all purpose" potential drugs work by
strengthening the immune system -- especially innate
immunity, which is less well understood that the more
familiar "adaptive" immunity involving T-cells (with which
the body quickly produces a customized response to a
particular invader, hopefully in time to cure the illness).
Invertebrate animals survive and fight infection with only
innate immunity.

Some of the approaches now being studied have long been
used in traditional or "alternative" medical treatments.
Others are far from ready for human test.

The AP story mentions:

* Certain cytokines and peptidoglycans that may stimulate
natural immunity. These approaches are being examined as
possible defenses against bioterrorism, including anthrax
or smallpox. If they work, they might have great impact on
more routine medical practice as well.

* "Androstene steroids" to block the action of cortisone
(according to the reporter's writeup, which we have not yet
checked further).

* Ways to correct the immune-system damage caused by
exposure to nuclear radiation. Success here might lead to
ways of strengthening the immune system in HIV, malaria,
and other diseases.

* A drug that acts like the popular supplement NAC (N-
acetylcysteine) may help treat certain bacterial toxins, by
reducing free-radical damage.

* Old remedies based on silver are now getting scientific
study, after one consistently worked as well as
tetracycline in laboratory tests against certain bacteria.

The new focus on bioterrorism will greatly stimulate
research on immune-based treatments, neglected traditional
medical approaches, and on completely new approaches as
well. It will bring in new people and resources, and move
with urgency and serious support -- no longer at the
leisurely pace of academic medical journals, or under the
commercial short-term focus on already-proven profit areas.
Here is the urgency we have long sought but seldom found.
The AIDS community should pay close attention.


***** Africa: Funding Sought for Epidemic Control

by John S. James

In the U.S. Congress, 8 Senators and more than 70
Representatives have signed a Dear Colleague letter seeking
1.2 billion dollars in emergency supplemental funding for
the global AIDS crisis. The letter will soon be sent to
President Bush.

Despite the great costs resulting from the September 11
attacks, the money is available, as the U.S. is now about
halfway through a $100 billion economic stimulus package.
This $100 billion needs to be spent anyway, on something,
in order to stimulate the U.S. economy. Less than 2% of
this money would cover the U.S. share of a good start on
global control of HIV/AIDS, tuberculosis, and malaria --
and encourage serious contributions from others.

For more information, including ways you can help, see the
Global AIDS Alliance,
http://www.globalaidsalliance.org


***** World AIDS Day Web Page

"To help journalists and others interested in HIV/AIDS
issues, the Kaiser Family Foundation has created a World
AIDS Day web page, http://www.kff.org/worldaidsday/ "

World AIDS Day is December 1. There is little central
organizing; instead, local agencies and communities do
their own events. As a result, there is no overall
calendar. Persons interested in events in their area should
check with local AIDS organizations.

The Kaiser Family Foundation page includes links to about
10 other Web pages on World AIDS Day.

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Associate Editor: Tadd T. Tobias, R.N.

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