When we sent this email issue yesterday, the message text was deleted for
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Here we are re-sending the text, without the attachment.

John S. James, AIDS Treatment News



AIDS TREATMENT NEWS Issue #375, December 21, 2001
phone 800-TREAT-1-2, or 215-546-3776

Contents

** Garlic Reduces Saquinavir Blood Levels 50%; May Affect
Other Drugs
Ordinary doses of a garlic supplement cut blood levels of
the protease inhibitor saquinavir in half, for reasons that
are largely unknown. Other protease inhibitors and other
antiretrovirals have not been tested. Patients and
physicians should be cautious about using garlic while on
any antiretroviral treatment, at least until more is known.

** NIH 7-Day On-Off Trial May Reduce Drug Side Effects,
Cost; Why It's Not Ready for Use
A 7-day on/off treatment regimen has kept HIV suppressed
for up to a year so far in carefully selected patients. But
the findings do not apply at all to most patients, and for
them the regimen is likely to be harmful. Researchers and
doctors agree that this approach is not ready for use
outside of carefully controlled studies.

**AIDS and Hepatitis News from ICAAC Conference: Phone
Overview, Web Reports
The most important news on both AIDS and hepatitis
treatment, from the ICAAC conference (December 16-19 in
Chicago), is available through a one-hour telephone
playback of a discussion by experts. Also, we show where to
find in-depth reports on the Web.

** HIV Testing 101 (Part 2 of 2)
This article looks at the reliability of HIV testing, and
answers arguments of AIDS denialists who say that HIV has
not been proven to exist, or does not cause AIDS, and that
HIV tests are unreliable. It also looks at detecting acute
HIV infection, the "detuned" antibody test for detecting
recent infection, and some of the issues around consent,
confidentiality, and anonymous HIV testing.

** AIDS TREATMENT NEWS New Publication Schedule
Starting in January we will publish 18 issues per year,
instead of twice monthly.


***** Garlic Reduces Saquinavir Blood Levels 50%; May
Affect Other Drugs

by John S. James

A study at the U.S. National Institute of Allergy and
Infectious Diseases found that garlic supplements reduced
blood levels of the protease inhibitor saquinavir by 51%.
The garlic preparation, an amount equivalent to about two
4-gram cloves per day, was taken for 21 days by healthy
HIV-negative volunteers. Then saquinavir was given for four
days, and compared to a baseline four-day saquinavir dosing
before the garlic was started.(1)

Later, after a 10-day washout with no saquinavir and no
garlic, the volunteers were given a third 4-day dose of
saquinavir. Even after 10 days off garlic, the saquinavir
blood levels after a third four-day dosing only reached 60-
70% of the original baseline blood levels -- indicating a
persistent effect of the garlic.

Other findings of this study are complex, and the mechanism
of this interaction is not clear. It probably involves the
body's CYP450 enzyme system, yet the garlic appears to be
affecting the oral bioavailability of saquinavir, not its
elimination from the body. And there were two distinct
groups of volunteers in how the garlic affected them. Most
had a big decline in saquinavir levels after the 21 days of
garlic use, with good recovery after the 10-day washout
period. But three volunteers did not have a significant
decline in saquinavir blood levels during the 21 days of
garlic use -- but did have a big drop after the washout.

It is not clear how other drugs besides saquinavir will be
affected. One study failed to find a statistically
significant interaction with ritonavir, which affects the
CYP450 enzyme system differently; however, that study used
only four days of garlic treatment.

Saquinavir study co-author Judith Falloon, M.D., said, "We
saw a definite, prolonged interaction. The clear
implication is that doctors and patients should be cautious
about using garlic supplements during HIV therapy."

Comment: Do Companies Care
If Their Drugs Work?

Clearly we need more drug interaction studies to guide
physicians and patients in how to use medications --
especially when there is reason to suspect an interaction,
or when a supplement is in wide use by those taking a
certain medication. Drug interaction studies are usually
small, inexpensive, and easy to do; this one, for example,
had only 10 volunteers (six women and four men -- one woman
was excluded from analysis due to lack of adherence), and
each volunteer took the drug for a total of 12 days,
reducing both side effects and expense.

We are fortunate that the U.S. National Institutes of
Health tested garlic, a supplement widely used by people
with HIV -- and found that it cut blood levels of
saquinavir in half. This interaction could lead to drug
failure and development of viral resistance, just as if
patients cut their doses in half before taking them.
Effects of garlic (and most other supplements) on other
protease inhibitors are currently unknown.

While NIH should be commended, we need to ask why
manufacturers don't do more interaction testing as a matter
of course. Antiretrovirals are premium products with huge
profit margins, costing thousands of dollars a year --
prices supposedly financing research and development. And
more importantly, these are critical medicines that can
determine whether patients live or die.

Yes, there are many supplements and even more approved
drugs, but not very many are widely used by persons with
HIV. And serious interactions are often fairly predictable
from what is already known about the pharmacology of the
drugs and supplements. Interaction testing is usually fast
and cheap -- and none need be done on antiretrovirals that
don't make it, only on those soon to be approved and
marketed. What is needed is ongoing strategic initiative to
identify potentially serious problems and spend a little
money to head them off before they happen -- not years
later.

Aside from the impact on human health, testing the most
obvious potential interactions would contribute to the
bottom line. Companies don't benefit when their drugs fail
and patients stop using them, and their doctors and other
doctors become less likely to choose those drugs for other
patients. After paying all the costs of developing
antiretrovirals and marketing them, when companies finally
get a chance to make a profit, they are throwing much of it
away.

The problem is that corporations do not act in their long-
term interests unless they are organized to do so. Groups
within companies are afraid of generating bad news. They
may not realize that this bad news is really good news,
because it allows them to make their drug more successful
in the real world by targeting those patients most likely
to benefit.

References

1. Piscatelli SC, Burstein AH, Welden N, Gallicano KD and
Falloon J. The Effects of Garlic Supplements on the
Pharmacokinetics of Saquinavir. CLINICAL INFECTIOUS
DISEASES. January 15, 2001; volume 34.


***** NIH 7-Day On-Off Trial

May Reduce Drug Side Effects, Cost; Why It's Not Ready for
Use

by John S. James

On December 4 researchers at the U.S. National Institute of
Allergy and Infectious Diseases published an early report
of their 7-day-on/7-day-off trial of antiretrovirals.(1)
This study found that a handful of selected patients, with
a selected antiretroviral regimen, were able to use the
drugs intermittently, with a schedule of 7 days on and 7
days off. They were able to maintain viral suppression for
32-68 weeks so far, with only half the drug use and clearly
reduced side effects. The researchers emphasize that this
regimen is not ready for use outside of controlled clinical
trials. The reasons are explained in the article, but not
in most news reports.

The Purpose of the Trial

The goal of this trial is to see if it is possible to
maintain HIV suppression with a reduced amount of
antiretroviral drugs, in order to reduce toxicity and cost.
There is no effort in this study to improve the treatment
by allowing some return of the virus in order to stimulate
the body's immune system against it.

Instead, this trial started with the observation that when
HIV is very well suppressed by antiretrovirals, and the
treatment is interrupted, it usually takes 2-3 weeks for
detectable virus to return. Since there is so little HIV
replication in that first week (assuming, of course, that
the virus had been very well controlled when treatment was
stopped), there should be little chance for the virus to
develop resistance in that first week off the drugs. Then
the treatment would be started again, keeping the virus
suppressed. So far it seems to be working in this 10-
patient proof-of-concept trial.

Cholesterol decreased 22% in this study, and triglycerides
decreased 51%, after 24 weeks of intermittent treatment --
probably because patients had less exposure to the drugs.
The researchers do not expect much change in lipodystrophy,
however.

Comment: Why It's Not Ready to Use

We are concerned that people may start trying treatment
interruptions without medical advice, in cases when it is
entirely inappropriate for them. Here are some facts to
consider:

* First and most important, all the volunteers in this
trial had very well suppressed virus before they began.
Viral load had to be below 500 copies for more than six
months, and below 50 copies when they started the trial;
also, they had to have a CD4 count of greater than 300. If
someone tried this intermittent schedule when their virus
was not suppressed, the whole idea of this trial would not
apply. Instead, the frequent interruptions would cause
periods of inadequate drug levels while the virus was
replicating -- excellent conditions for the development of
viral resistance.

* Also, all the volunteers in this trial received a four-
drug regimen "selected to provide potent antiretroviral
therapy with a high genetic barrier to the development of
drug resistance" -- d4T, 3TC, indinavir, and a small dose
of ritonavir (mainly to keep the indinavir in the blood
longer). As an extra precaution, the last dose of ritonavir
before each treatment interruption was not given, in order
to clear the indinavir from the body faster.

* In addition, a research study can test viral load and
other blood levels frequently, to detect treatment failure.
Once a patient waited only three extra days to resume
treatment (10 days instead of 7), and as a result had a
viral load of over 3,000 copies. He was able to continue
the study and regain viral suppression, but this case
illustrates that control of HIV with this treatment
schedule may leave little room for error.

* We still need to know whether this schedule works in
longer-term use, whether it works in more advanced
patients, and whether it can be used with other
antiretroviral regimens. But the proof-of-concept trial
suggests that when more is known, intermittent treatment
might significantly reduce both cost and toxicity of
antiretroviral therapy, and help to make it available in
developing countries where cost is a major obstacle.

References

1. Dybul M, Chun T, Yoder C, and others. Short-cycle
structured intermittent treatment of chronic HIV infection
with highly active antiretroviral therapy: Effects on
virologic, immunologic, and toxicity parameters.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES USA, Early
Edition online (December 4, 2001).


***** AIDS and Hepatitis News from ICAAC Conference: Phone
Overview, Web Reports

A one-hour review of the most important AIDS and hepatitis
news at the 41st Conference on Antimicrobial Agents and
Chemotherapy (ICAAC, Chicago, December 16-19) is available
without charge through a toll-free phone number. You can
hear a recording of a one-hour teleconference with leading
experts, which took place in the evening of December 18.

To hear the recording, call 800-428-6051; when asked to
enter a code, it is 212440. No registration is required.

This teleconference was organized by HIVandHepatitis.com,
with unrestricted educational grants from Roche
Laboratories, Inc., and Bristol-Myers Squibb Corporation.

Web Reports

Original written reports are being posted on several Web
sites, including:
http://www.thebody.com
http://hiv.medscape.com/ (one-time registration required,
but it's quick and free)
http://www.hivandhepatitis.com
http://www.natap.org

Also, you can find the official site through
http://www.icaac.org -- select "Annual ICAAC", then select
"Program and Abstracts online" for the 41st ICAAC (the 2001
conference). You will need to give your email address and
choose a password to use this site. There is plenty of
AIDS-related information; for example, a search for 'HIV'
in the abstract text returns almost 200 abstracts. You
might need to create an "itinerary" to view the abstracts;
if so, the software can be confusing.


***** HIV Testing 101 (Part 2 of 2)

by Bruce Mirken

[Note: Part 1 of this article appeared in AIDS TREATMENT
NEWS #374, November 23, 2001.]

Detecting Acute HIV Infection

Shortly after getting infected with HIV, many patients have
an acute (or "primary") HIV infection, a period of flu-like
illness with symptoms like fever and malaise that could be
caused by influenza or many other diseases. Many scientists
and physicians believe it is important to treat during
acute this HIV infection (provided, of course, that it gets
diagnosed then). But there are still questions remaining
about treating acute infection.(1,2)

To confirm an acute HIV infection in symptomatic
individuals with potential HIV risk factors, current
guidelines(2) recommend use of HIV RNA (viral load) tests.
[The regular HIV antibody test will not detect acute HIV
infection because the patient is still in the "window
period" before antibodies have been produced.] False
positives can occur with viral load tests, but a review of
the data in the August, 1999 AMERICAN FAMILY PHYSICIAN(1)
suggests it is usually possible to differentiate these from
the real thing: "During the symptomatic phase of acute HIV
infection, the viral RNA shows in excess of 50,000 copies
per mL. Three instances of false-positive HIV-1 RNA tests
have been reported; in each instance, however, the person
was not having symptoms and the viral load [reported] was
less than 2,000 copies per ml. The presence of high-titer
HIV-1 RNA (more than 50,000 copies per mL) in the absence
of HIV antibodies establishes diagnosis of acute HIV
infection."

At present there is no viral load test approved by the FDA
for the purpose of diagnosing HIV infection in individual
patients. In September the FDA did approve a viral load
test developed by National Genetics Institute for screening
large pools of donated blood plasma.

If viral load testing is not available, current treatment
guidelines(2) recommend testing for p24 antigen, a viral
protein. In either case, the diagnosis should be confirmed
by antibody testing once the window period has elapsed.

"Detuned" ELISA

A variation of standard antibody testing, presently
approved in the U.S. only for research, is the
sensitive/less sensitive or "detuned" ELISA. The detuned
test takes advantage of the fact that antibody levels rise
in a predictable pattern during roughly the first four to
six months after infection, eventually reaching a plateau
that often stays roughly constant for many years.

Current ELISAs can detect relatively low levels of
antibodies. The detuned testing approach involves taking
samples that are confirmed HIV-positive by these tests, but
then retesting them with a less sensitive, diluted ELISA.
This less sensitive test can only detect antibodies at the
higher levels achieved during the period six months or more
after infection. Thus, the detuned approach distinguishes
between recent and established infections, so it is a
potentially valuable tool for epidemiologists trying to
chart the pattern of new infections. It is not used in
patient care at this time.

Accuracy of Antibody Testing --
and Denialist Arguments

Constantine(3) sums up the general consensus among experts
and institutions such as the CDC when he says "The antibody
tests are nearly 100 percent sensitive (unless a person is
in the window period) and about 99 percent specific." Such
levels of accuracy have been documented in a number of
studies, including periodic evaluations of commercially
available test kits conducted by the World Health
Organization.

Still, AIDS denialists (the self-styled "AIDS dissidents"
who claim that HIV is either harmless or doesn't exist)
continue to claim that HIV antibody tests are unreliable.
Many of their arguments seem to derive from a series of
articles written by Christine Johnson in the mid-1990s,
several of which are available on denialist web
sites.(4,5,6)

Johnson's argument boils down to two key points: 1) HIV has
never been properly isolated, so the HIV proteins used in
the tests haven't been proven to actually come from HIV, 2)
Even if HIV is real, the proteins are not unique and cross-
react with many other antigens, rendering a positive result
meaningless. Johnson's list of some 60 factors she
describes as "known to cause false-positive HIV-antibody
test results" turns up regularly in denialist literature.

The claim that HIV has never been properly isolated, based
on the writing of a group in Perth, Australia, is too
technical and complex to examine thoroughly here. However,
it is elegantly demolished in Michael Coon's article, "HIV,
AIDS and the Distortion of Science," available on the AEGIS
web site.(7) In short, Coon argues that the Perth Group set
up artificial, phony criteria for "proof" of HIV's
isolation that bear no relation to how virology works in
the real world.

The second argument, though, contains a grain of truth.
Cross-reactions are possible, and a number of factors can,
on occasion, produce false-positive HIV antibody test
results. What Johnson fails to address in any detail is
that such effects are typically transient and rare,
affecting few individuals.

For example, one well-known cause of false-positives
Johnson lists is influenza vaccination.(8,9) But she
neglects to mention that a key reference she cites
described the phenomenon as "infrequent" and "of short
duration," while in another only 10 false-positives were
found among 133,000 individuals who had flu shots prior to
testing, with half of those reverting to negative within
six months.(9)

Constantine adds, "I doubt very much that it has been
firmly documented that 60 factors can interfere with
antibody tests. In fact, it has been long sought to try and
identify the causes of false positive results, and only a
few have really been documented to consistently interfere
(e.g. pregnancy, certain autoimmune diseases, some
infectious diseases). However, even these do not
consistently cause problems with the tests... There are
very few false positives that can't be resolved with
further testing."

Consent, Anonymity, and Counseling

(1) Anonymous Testing

Prior to HIV, blood testing was considered a routine
procedure, with such minimal dangers that formal informed
consent was rarely required. But because HIV presented
massive psychosocial risks, from employment discrimination
to rejection by family and reduced access to health care,
special procedures were widely adopted.(10) These included
specific informed consent and pre- and post-test
counseling. Many states set up test sites where people
could get tested anonymously, without ever giving their
name.

Anonymous testing (other than the home test, below) was
never universally available, Morin notes, but was and is
offered in many places, despite the recent move by numerous
states to adopt a system of names-based HIV reporting (a
few, including California, are implementing HIV reporting
via codes that don't reveal the person's name). The CDC and
others urged that the option for anonymous testing should
be kept available, believing fear of disclosure would keep
some from being tested, and most states have followed this
recommendation.

Because local laws and procedures vary, Morin recommends
that anyone concerned about anonymity or disclosure contact
their local health department to check. A number of AIDS
service organizations operate hotlines, which should also
be able to provide this information.

Those living in areas with no anonymous test sites can
still be tested anonymously via home collection test kits,
which are sold in many drug stores. Introduced in the mid-
'90s, the kits were controversial because counseling is
provided by telephone rather than in person. Morin says
fears that telephone counseling would prove inadequate
haven't been borne out, but sales of the kits have been
less than expected. Still, "the FDA ruled that you cannot
bar their sale in any state, so even in states that don't
have anonymous testing people can use home test kits to
anonymously be tested," he says.

But, he adds, things change when the individual seeks
treatment: "If you go to your doctor and the doctor does a
viral load test, you get reported through the viral load
test to the health department. So there's no way to keep
treatment for HIV anonymous."

(2) Consent and Counseling

As with anonymity, requirements for consent and counseling
vary from state to state. Most, but not all, states require
specific informed consent -- sometimes in writing -- for
HIV testing. Approximately one-fifth of states require pre-
test counseling, with many listing specifically what that
counseling must include. The U.S. Department of Health and
Human Services recommends that all HIV testing include
counseling that covers the test itself, basic information
about HIV and AIDS, how to avoid spreading the virus, the
confidentiality of the results, the possible impact of the
results on the person being tested, and discussion of to
whom results should be disclosed, such as sex or needle-
sharing partners.(11) Counselors should also be able to
give referrals to medical and psychosocial support
services.

Counseling and consent procedures vary greatly, remain
controversial and may continue to change. Even states that
require informed consent may allow HIV testing without
consent in special circumstances. For example, many permit
involuntary testing of a patient when health workers have
been exposed to the person's blood. Some test prisoners or
people accused of sex crimes, and at least two, New York
and Connecticut, require mandatory testing of newborns,
which indirectly reveals the mother's HIV status, but does
not tell if the infant has been infected.

In October 2000 the Institute of Medicine recommended that
HIV testing be included as a routine part of prenatal care.
Women would be informed of the test and could opt out, but
specific consent would not be required. Thus far the U.S.
Public Health Service has stopped short of urging an end to
informed consent in such cases, simply suggesting that
providers recommend HIV testing to all pregnant patients.

References

1. Perlmutter, Barbara Lee et al, "How to Recognize and
Treat Acute HIV Syndrome," AMERICAN FAMILY PHYSICIAN,
August, 1999, http://www.aafp.org/afp/990800ap/535.html.

2. U.S. Public Health Service, "Guidelines for the Use of
Antiretroviral Agents in HIV-Infected Adults and
Adolescents" (August 13, 2001),
http://www.hivatis.org/trtgdlns.html.

3. Constantine, Niel, "HIV Antibody Assays," HIV KNOWLEDGE
BASE, HIV InSite Sept. 2001,
http://hivinsite.ucsf.edu/InSite.jsp?page=kb-02-02-01.

4. Johnson, Christine, "Whose Antibodies Are They Anyway?"
CONTINUUM, Sept./Oct., 1996,
http://www.virusmyth.net/aids/data/cjtestfp.htm.

5. Johnson, Christine, "Is Anybody Really Positive?" HEAL
MAGAZINE, 1995,
http://www.virusmyth.net/aids/data/chjtests2.htm

6. Johnson, Christine, "Playing Russian Roulette in the
Laboratory," Virusmyth,
http://www.virusmyth.net/aids/data/chjroulette.htm.

7. Coon, Michael, "HIV, AIDS and the Distortion of
Science," Misc Health AIDS, August, 2000,
http://www.aegis.org/topics/hiv_exist.html.

8. MacKenzie, William, et al, "Multiple False-positive
Serologic Tests for HIV, HTLV-1 and Hepatitis C Following
Influenza Vaccination, 1991," JOURNAL OF THE AMERICAN
MEDICAL ASSOCIATION, Vol. 268, No. 8, Aug. 26, 1992, p.
1015-1017.

9. Arnold, NL, and others. "Donor Follow-up of Influenza
Vaccine-Related Multiple Viral Enzyme Immunoassay
Reactivity," VOX SANG, Vol. 67, No. 2, 1994, p. 191-194.

10. Wolf, Leslie, and Lo, Bernard, "Ethical Dimensions of
HIV/AIDS," AIDS KNOWLEDGE BASE, HIV InSite,
http://hivinsite.ucsf.edu/InSite.jsp?page=kb-08-01-05.

11. U.S. Department of Health and Human Services,
"Voluntary HIV Counseling and Testing: Facts, Issues and
Answers,"
http://hivinsite.ucsf.edu/InSite.jsp?doc=2098.2099&page=pr-04-03.

12. Food and Drug Administration, "HIV and AIDS,"
http://www.fda.gov/oashi/aids/test.html (this regularly-
updated page contains information about FDA actions
relating to HIV-related tests).


***** AIDS TREATMENT NEWS New Publication Schedule

by John S. James

AIDS TREATMENT NEWS has traditionally published 24 issues
per year. But in 2001 we ran behind and will only publish
19 issues.

Starting in 2002 we are changing our publication frequency
-- from twice monthly to 18 issues per year. We may publish
more than 18 issues.

Enough news is happening today to fill several newsletters,
and we could easily write 24 issues per year. The problem
is information overload. Because so much work is being done
now, there is more background and context that reflects on
the importance and credibility of research findings and
other news. The most important reporting today will need
time for investigating and understanding this background.


***** AIDS TREATMENT NEWS

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email: aidsnews@...
useful AIDS links: http://www.aidsnews.org

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

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treatments, especially those available now. We interview
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AIDS Treatment News
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