AIDS TREATMENT NEWS Issue #394, September 12, 2003
phone 800-TREAT-1-2, or 215-546-3776

CONTENTS:

** WTO Accepts Rules Limiting Medicine Exports to Poor Countries
In a controversial decision on August 30, 2003, the World Trade
Organization agreed to complex rules limiting the export of
medications to developing countries. Reaction to the decision so
far has shown a complete disconnect between trade delegates and
the WTO, both of which praise the new rules as a humanitarian
advance, and those working in treatment access in poor
countries, who believe that they will effectively block
treatment from reaching many who need it. We have prepared a
background paper that analyzes this decision and its
implications and offers the opinions of key figures on both
sides of the debate.

It is clear that the rules were largely written for and probably
by the proprietary pharmaceutical industry, and imposed on the
countries in the WTO mainly by the United States. The basic
conflict is that this industry does not want the development of
international trade in low-cost generic copies of its patented
medicines -- not even for poor countries where little or no
market exists. Yet millions of people die each year without
medication for treatable conditions such as AIDS, and drug
pricing remains one of several major obstacles to controlling
global epidemics.

** Nevirapine Reduced Mother-to-Child Transmission Better Than
AZT -- At 70 Times Less Cost
A follow-up of a Uganda study shows that a single dose of
nevirapine to the mother in labor and a single dose to the
infant shortly after birth continues to show excellent results
when the infants reach 18 months -- despite breast feeding for
99% of the infants, and some HIV transmission that occurred as a
result.

** Treatment Interruption: Study Found Poor Result for Highly
Treated, Highly Resistant Patients
A four-month treatment interruption did not help patients who
were not controlling their virus because it had extensive
resistance to HIV drugs.

** New Guidelines for Avoiding Heart Disease by Managing High
Cholesterol, Triglycerides, or Related Problems in HIV
These guidelines, based on new heart guidelines for the general
public and including HIV-specific issues, have many useful
suggestions.


***** WTO Accepts Rules Limiting Medicine Exports to Poor
Countries

by John S. James

On August 30, 2003, a World Trade Organization (WTO) meeting in
Geneva, Switzerland adopted new rules on exporting generic
copies of patented drugs to poor countries. The WTO and some of
its trade delegates presented these rules as a grand
humanitarian solution that will now make AIDS and other
medicines more available to the poor. In fact, almost everything
in the texts was written on behalf of multinational
pharmaceutical corporations, and demanded for their benefit by
the United States and to a lesser extent by European and other
rich countries. The pharmaceutical industry, with the U.S.
government in tow, won the decision by splitting the richer from
the poorer developing countries and bringing great pressure to
bear, while most of the international-trade establishment just
wanted this issue off the table one way or another.

Organizations actually providing treatment in developing
countries fear that the new system will obstruct access, and
that poor countries that cannot manufacture their own
pharmaceuticals will be worse off in the future. Médecins sans
Frontières (Doctors Without Borders, the worldwide relief
organization that won a 1999 Nobel prize for its work) and Oxfam
(a major British famine-relief organization) said in a joint
press issued August 30, 2003, "Today's WTO agreement that is
ostensibly intended to get drugs to the poorest countries does
not provide a workable solution. [It] was designed to offer
comfort to the U.S. and the Western pharmaceutical industry....
Unfortunately, it offers little comfort for poor patients.
Global patent rules will continue to drive up the price of
medicines.... Yesterday, over twenty developing countries were
voicing concerns about the text. Today, they have come under
tremendous pressure to adopt it. However, this disappointing
outcome must not prevent countries from immediately taking
measures that are allowed under WTO patent rules in order to
access affordable medicines and save lives."

The one victory of the developing countries was the elimination
of a disease list -- which would have banned all pharmaceutical
exports of generic copies of patented drugs for any disease
except AIDS, tuberculosis, malaria, and a short list of others,
mostly tropical infections that are not commercially important
in rich countries. If the U.S. had had its way, exporting
generics of patented drugs for cancer, diabetes, asthma, and
almost all other diseases, even to the world's poorest
countries, would have been flatly prohibited. In December 2002
the U.S. alone blocked world agreement at another World Trade
Organization meeting by demanding the disease list. But
developing countries would not accept it, so the proprietary
pharmaceutical industry decided to change its strategy and rely
on other restrictions instead.

The most important fact about all pharmaceutical trade rules is
that in case of a catastrophic emergency in the U.S. or other
powerful countries, such as a major chemical or biological
attack or deadly epidemic, these countries will do whatever they
need to do, and none of the rules will be worth the paper they
are written on. But this basic assurance is not available to
developing countries, for whom over 20 million dead of AIDS does
not rise to that level of emergency. If rich and powerful
governments did not have a pass when it counts, but were truly
bound by the rules they make others obey even at the sacrifice
of lives, then the entire design and content of the rules would
be different -- a central reality known to all but usually
absent from analysis and discussion.

See our References below for links to the full text of the
August 30 agreement [1, 2], the WTO August 30 press release [3],
and to the Doha Declaration [4], a WTO agreement two years ago
that trade rules should not prevent countries from protecting
public health.

Historical Context

Most new medicines are patented for up to 20 years, and patent
holders can charge any price they want -- commonly $10,000 or
more per patient per year for HIV treatment in the United States
(up to 20 times what a generic manufacturer could charge and
still make a profit). Because they are new, all antiretrovirals
are patented in rich countries, and in most other countries
where a viable market could exist. Usually patent holders have
no incentive to market their drugs in poor countries -- but do
not want generic manufacturers or anyone else doing so, because
the example of low-cost drugs might upset their markets in rich
countries, especially the U.S. Millions died without treatment
in poor countries while the issue of treating them with patent-
protected drugs (the only ones available) was mostly kept off
the table until about four years ago.

Patent laws are national, not international, but the trade
agreement that formed the WTO demands that all countries conform
their patent laws to the European system, and include patents on
pharmaceuticals, which had not been required before 1995.
Developing countries were given until 2006 to change their
patent laws to comply fully with the new rules (recently
extended to 2016 for least-developed countries); this is why
India, for example, can manufacture and export AIDS drugs today.
(India allows patenting of a drug manufacturing process but not
of the final molecule -- a successful system to encourage
domestic industry to compete in low-cost drug production. But
India will have to change its patent laws by 2006, and then
generic exports of new medicines will no longer be allowed
except under the new rules just adopted.)

Existing WTO rules allow a country to use "compulsory licensing"
(granting the right to manufacture a patented product without
the patent-holders consent) under certain conditions -- and to
_import_ a drug under a compulsory license. But these rules also
say the drug must be manufactured primarily for domestic use --
so starting in 2006 or some time before then, there might be no
one legally able to _export_ the drug even to a country allowed
to import it. Since poor countries usually cannot pay the
patent-holder's price, and cannot make the drugs domestically,
how could their people obtain new pharmaceutical treatments?
This "export problem" has been a major trade controversy for
over two years, and was the reason for the WTO meeting of 146
countries that just adopted the new rules.

In November 2001 all countries in the WTO accepted the landmark
"Doha Declaration," which said, "We agree that the TRIPS
agreement [the WTO's intellectual property rules] does not and
should not prevent members from taking measures to protect
public health." The August 30 rules were supposed to implement
the Doha Declaration, but instead they restricted it. For
example, the 10 nations that hope to join the European Union
(mostly poor countries in Eastern Europe) "agreed that they
would only use the system as importers in situations of national
emergency or other circumstances of extreme urgency" [2] until
they join the EU -- and then that they will not import generic
versions of patented pharmaceuticals even in such an emergency.
(The countries are Czech Republic, Cyprus, Estonia, Hungary,
Latvia, Lithuania, Malta, Poland, Slovak Republic, and
Slovenia.) Pressuring these countries not to respond even to a
national emergency in order to protect profits of pharmaceutical
companies is hardly an "implementation" of the Doha Declaration
that trade rules should not prevent countries from protecting
public health.

Reactions For and Against the New WTO Export Rules

Here are some quotes that show the great differences of opinion
about the new trade rules on pharmaceuticals. Basically,
everyone says that they want to help poor countries get
treatment -- but that is where the semblance of agreement ends.

The following background will help those not familiar with this
complex issue to understand the quotes below:

* The WTO ratifies decisions by unanimous consensus of all 146-
member countries. But the actual decisions are made in small,
secret meetings set up by the U.S. and other powerful countries,
to craft agreements that they want, and may be able to get
through the whole body. Then great pressures are used to bring
everyone into line -- especially by the world's only superpower,
whose decisions affect every country in countless ways.

* In this case five countries negotiated the text that the
others had to accept or reject without change; these countries
were the U.S., Brazil, India, Kenya, and South Africa. Clearly
the U.S. had the most instruments of pressure at its disposal.
The other four countries will be able to produce many
pharmaceuticals domestically, so the lives of their citizens
were not at stake in the decision, as they are for many poor
countries. India will lose some business if the rules prove
mostly unworkable -- but its potential revenue from sales to the
poorest countries is not great, and far less than its potential
sales to the U.S. [5] (provided India stays on good terms with
the superpower). And once these four countries accepted the U.S.
demands, they were removed as potential leaders of any movement
by developing countries to get an agreement more in their
interest.

* Once a government has accepted a WTO agreement (for any
reason), it is not going to criticize it in public, no matter
what it thinks internally. Therefore official statements from
rich and poor countries alike can be expected to be supportive.
Those who work in health care in developing countries may or may
not be free to speak publicly about what they know.

* The U.S. and some international press, unfamiliar with the
background of this issue, mainly reported the WTO position,
presenting the new rules as a great humanitarian advance. But
activists working in the area see the whole point of this
agreement as stopping the development of low-cost trade among
poor countries in generic versions of medicines protected by
patents in rich countries -- sacrificing lives to protect a
dysfunctional business model that denies new medical advances to
most of the people who need them.

* Poor countries even more than rich ones had strong incentives
to get this issue out of the way before the crucial WTO meeting
beginning September 10 in Cancún, Mexico. They desperately want
reforms in other areas, especially agricultural trade rules.
Rich countries spend over $300,000,000,000 (300 billion dollars)
every year supporting their farmers [6], mostly big corporations
-- undercutting lower-cost producers in developing countries that
cannot pay such support, and keeping whole nations and
regions in poverty.

* "TRIPS" is the "Trade-Related Aspects of Intellectual Property
Rights," the part of the WTO agreement that deals with patent,
copyright, and related laws; it took effect on January 1, 1995.
Though TRIPS was designed with no thought whatever to its effect
on access to AIDS or other treatment in poor countries, it does
contain general safeguards that activists have used to argue for
access, or against worse restrictions (sometimes called "TRIPS-
plus") that the U.S. is imposing through other treaties. For
technical background on TRIPS, see:
http://www.wto.org/english/tratop_e/trips_e/trips_e.htm

* Almost all patents are held in rich countries (for reference
and discussion see BMJ (BRITISH MEDICAL JOURNAL) September 13,
2003,
http://bmj.com/cgi/content/full/327/7415/571?etoc

Therefore pharmaceutical patents bring no commercial benefit to
most poor countries but only raise the prices of drugs -- or
more likely exclude all but the elite from new medicines
entirely. Patents can help motivate research and development of
new drugs -- but only for those who can buy them at high prices.

* The August 30 agreement is temporary, to be replaced by mid
2004 with a permanent amendment to TRIPS that "will be based,
where appropriate, on this Decision" [2]. So the issue must be
revisited next year. There may be no real test of the rules by
then, however -- since legally these rules act by providing a
waiver of an existing WTO rule, and the countries that have been
exporting AIDS drugs will not need the waiver by that time. On
the other hand, a generic manufacturer in a rich country that is
already required to comply fully with TRIPS (such as Canada,
where at least one company has been interested in producing AIDS
medicines for poor countries but has been blocked by Canadian
law) might be able to use the new WTO rules now. (In this
instance, Canada would need new legislation before any of its
generic companies could try to use compulsory licenses -- and
the much richer proprietary pharmaceutical industry that largely
wrote these rules would probably oppose such amended
legislation.)

* An urgent task now and for the next year is to find
possibilities that might work under the new rules (or work
around them) to deliver treatment to poor countries, and make
sure that critical doors are not closed when the permanent TRIPS
wording is devised. The final wording might not be public until
just before the vote, but still health activists can educate the
international-trade community about what provisions are most
important for access to medical care, and why they matter.

Range of Views on the Issue

* "The two decisions that the General Council reached today --
the Motta text [1] [named for a WTO official] and the Chairman's
statement [2] -- will ensure that the system will not be abused.
The additional clarifications contained in the Chairman's
statement [The General Council Chairperson's Statement] add
strong provisions to prevent diversion, and increase the
likelihood that the solution will benefit patients in the
world's poorest countries as envisioned in the Doha Declaration.
Taken as a whole, this solution reaffirms the critical role of
patents in the development of new medicines." -- Pharmaceutical
Research and Manufacturers of America (PhRMA), August 30, 2003
press release. [IFPMA, the International Federation of
Pharmaceutical Manufacturers Associations, also released a press
statement supporting the decision.]

* Law professor and Health GAP member Brook Baker explained the
procedures that will be required under the new rules: "In order
to import medicines in a country where a drug has been patented,
the following steps must be followed: (1) the importing country
must seek a voluntary license on commercially reasonable terms
for a commercially reasonable period of time; (2) failing that
someone must apply for a compulsory license; (3) if the
compulsory license is for import, the importing country must
assess its generic industry's capacity to produce the medicine
locally; (4) if capacity is insufficient, it must notify the WTO
of its decision and explain and justify its decision re capacity
in detail; (5) the importing country must notify a potential
exporter; (6) that exporter must in turn seek a voluntary
license on commercially reasonable terms for a commercially
reasonable period of time; (7) that exporter must seek a
compulsory license from its own government on a single-country
basis; (8) compensation by royalty must be set based on
standards of reasonableness in the importing country; (9) if a
license is granted, the exporter must investigate pill size,
shape, coloring, labeling, and packaging of the patent-holder's
product in the importing country and differentiate its new
product in all respects, regardless of cost; (10) obviously, the
generic producer will need to seek product registration and
prove bio-equivalence based on a pill of different size and
shape. This process must be fulfilled over and over again for
each and every drug and for each and every country to which the
drug will be exported. This procedural nightmare may create a
cottage industry for lawyers, but it will not expedite the
delivery of affordable medicines to people dying of treatable
diseases." -- "Vows of Poverty, Shrunken Markets, Burdensome
Manufacturing and Other Nonsense at the WTO," August 28, 2003,
http://lists.essential.org/pipermail/ip-health/2003-August/005176.html

* "All people of good will and good conscience will be very
happy today with the decision that the WTO members have made.
It's especially good news for the people of Africa who
desperately need access to affordable medicine." -- Kenyan
Ambassador Amina Chawahir Mohamed, quoted in THE WASHINGTON
POST, August 31, 2003.

* "America is arm-twisting. It's a triumph for corporate greed."
-- Gitura Mwaura, chair of the Kenya Coalition for Access to Essential
Medicines, quoted by Reuters, August 28, 2003 and
published in THE NEW YORK TIMES. Another Kenyon quoted in the
same article, Gichinga Ndirangu, trade communication manager for
the Heinrich Boll Foundation in Nairobi, said "they just
outflanked the developing countries."

* "This will absolutely save millions of lives that would be
lost without it." -- Faizel Ismail, South Africa's
representative to the WTO, THE NEW YORK TIMES, August 31, 2003.

* "The sense is really that it is way too much red tape, and
that it is not a feasible solution to the problem." -- Jonathan
Berger, AIDS law project at Witwatersrand University,
Johannesburg, South Africa, quoted by Reuters, August 28, 2003.

* "We are under tremendous pressure. It's a question of whether
other countries will assent to the fact that this is as far as
the U.S. government is willing to go. The deal is on the table
and the U.S. attitude is, 'Take it or leave it.'" -- Trade
ambassador from "a large Asian country whose government had
raised concerns about the plan," THE WASHINGTON POST August 30,
2003.

* "You cannot expect every poor country in the world to produce
lifesaving drugs. There is no question that to get access, we
are going to have to allow countries to import generic drugs
from richer countries." -- Michael H. Merson, dean of the public
health school at Yale University, quoted in THE WASHINGTON POST,
August 30, 2003.

* "The solution could have been very simple and straightforward,
using a model such as the World Health Organization and other
experts have suggested. The complexities imposed by rich
countries are designed to uphold drug company monopolies and to
discourage widespread generic competition in poor countries." --
Gaelle Krikorian, Act Up-Paris, joint press release by ACT Up
Paris and Health GAP, September 11, 2003.

* "No matter how desperate the health need, a developing country
without the capacity to produce a needed drug (which is
virtually all of them) will have to ask another government to
suspend the relevant patent and license a local company to
produce and export it. Few countries, if any, will be prepared
to help other countries in this way, as it would provoke
retaliation by the US which fiercely defends the commercial
interests of the pharmaceutical corporations.

"Furthermore, the agreement is wrapped in so much red tape that
it becomes largely unworkable - it amends a clause of only 20
words, yet runs to more than seven whole pages. In practice,
most poor countries will end up paying the high price for
patented medicines or, most probably, doing without." -- Oxfam,
"WTO Patent Rules Will Still Deny Medicines to the Poor," press
statement August 27, 2003.

* "The current decision is only a temporary waiver, and a
permanent amendment to the TRIPS is scheduled for 2004. We call
upon the WTO member countries to draft an amendment to the TRIPS
that simplifies and clarifies the procedures and removes
unnecessary obstacles to the export of medicines to address
public health problems." Joint statement on TRIPS and public
health, September 10, by 14 non-government organizations in
Cancún: ACT Up Paris; Consumer Project on Technology; Consumers
International; Essential Action; European AIDS Treatment Group;
Health Action International; Health GAP; International People's
Health Council; Médecins sans Frontières; OXFAM International;
People's Health Movement; SEATINI; Third World Network; Women in
Development

* "They're playing with fire. The sensitivities of this are
obvious and we're right on the edge here." -- Jon Huenemann,
former U.S. assistant trade representative, quoted in THE WALL
STREET JOURNAL, September 5, 2003 on Brazil's plan to use
compulsory licensing to authorize government importing of three
generic drugs for HIV (efavirenz, lopinavir, and nelfinavir)
until it can make sufficient quantities domestically, unless the
patent holders will give Brazil a larger discount. Brazil now
pays 63% of its AIDS drug budget for these three alone. [For
technical reasons Brazil's plans are not directly related to the
new WTO rules; we included this quote to show the emotion around
the issue.]

In 2001 the U.S. itself threatened to use compulsory licensing
of pharmaceuticals (which it normally opposes) to import a
generic version of an antibiotic for anthrax at a lower price,
when the drug was under patent in the U.S. but not in other
countries. AIDS has killed over a million times more people than
the anthrax attacks in the U.S.

Comment

Today epidemics are more dangerous than before, due to higher
population densities and greatly increased long-distance travel.
At the same time scientific and medical advances offer more
opportunities than ever to control disease and enable people to
live longer and healthier lives. The key stumbling block is the
lack of political will to deal with illnesses that mostly affect
the poor. It is appalling that instead of responding to these
problems and opportunities, the WTO has adopted language clearly
written by industry to prevent "South-South" (poor country)
generic trade in new medicines, eliminating or greatly
restricting some of the most useful options for public health
before they even come into view.

The problem of diversion of the drugs for the poor into rich
countries (a main argument for the new rules) is mostly a
smokescreen. Diversion has been minor and easily controlled,
since the pills of all legitimate manufacturers must already
look different. But even if this issue were significant,
governments and the WTO should prioritize public health over
corporate revenue.

The biggest single obstacle to global health today is lack of
resources -- including funding, infrastructure, training, and
rational procurement and distribution systems for medicines.
Pharmaceutical patents -- and the worldwide dark cloud of
restrictions that flow from them, blocking medical research as
well as access to treatment -- may be number two or three. Both
have a common root in the lack of political will.

The central problem in AIDS is political, as it has always been.
No law of nature prevents the most powerful business and
government leaders from applying their influence and creativity
on behalf of the common good as well as private interests. A
completely different perspective is possible. If people could
organize the political and institutional will to save lives and
make systems that work for everyone, then it would not be hard
to assemble the needed resources, build medical infrastructure,
deal with stigma, trade restrictions, and other problems, and
get the global epidemics under control.

Note: Kate Krauss of AIDS Policy Project
[ http://www.aidspolicyproject.org ] contributed to this article.

References

(1) Text of "Implementation of Paragraph 6 of the Doha
Declaration on the TRIPS Agreement and Public Health" -- rules
limiting medicine exports, adopted August 30, 2003:
http://www.wto.org/english/tratop_e/trips_e/implem_para6_e.htm
(Also see reference 2, below.)

(2) Additional rules favoring pharmaceutical companies were
issued in "The General Council Chairperson's Statement," August
30, 2003:
http://www.wto.org/english/news_e/news03_e/trips_stat_28aug03_e.htm

(3) World Trade Organization press release, August 30, 2003:
http://www.wto.org/english/news_e/pres03_e/pr350_e.htm

(4) Full text of the November 2001 Doha Declaration on the TRIPS
Agreement and Public Health, November 20, 2001:
http://www.wto.org/english/thewto_e/minist_e/min01_e/mindecl_trips_e.htm

(5) THE ECONOMIST, September 6, 2003, "Indian Pharmaceuticals:
Patently Ambitious," page 56.

(6) The $300 billion figure is from THE ECONOMIST, September 6,
2003, "The Cancun Challenge," pages 59-61.


***** Nevirapine Reduced Mother-to-Child Transmission Better
Than AZT -- At 70 Times Less Cost

A single dose of nevirapine given to an HIV-positive woman
during labor, and a single dose given to her infant soon after
birth, reduced HIV transmission 41% better than AZT when the
infants were age 18 months, in a study conducted by researchers
at Makerere University in Kampala, Uganda, and at the U.S.
National Institute of Allergy and Infectious Diseases (NIAID)
[1]. About 26% of the children in the AZT group were infected by
18 months, vs. about 16% of children in the nevirapine group.
The AZT regimen consisted of one or more doses to the women
during labor, and twice-daily doses to the infants during their
first week. The simpler nevirapine treatment cost about 70 times
less than the AZT treatment.

Nevirapine did not seem to have any long-term antiviral effect.
Rather, it gave better early protection when the infants were
most vulnerable to infection. After the treatment, infants in
both groups continued to get infected at about the same rate due
to breastfeeding, which most of the women had stopped by 18
months (the average time breastfeeding was nine months).

An accompanying editorial suggested that two to three days of
AZT plus 3TC could be added to the mother's treatment to prevent
development of viral resistance to nevirapine, which can happen
when even a single dose of nevirapine is used alone. Or, much
better, the mothers could be started on combination
antiretroviral treatment [2].

About 800,000 children are infected with HIV each year through
mother-to-child transmission, and hundreds of thousands of these
cases could be prevented. Cost of the nevirapine is not the
problem. The main obstacle has been funding and implementing the
programs to use it (which usually require testing, counseling,
dealing with stigma such as violence against women who test
positive, staff training, prenatal care, and associated
infrastructure). Only about 1% of Africans now have access to
services for prevention of mother-to-child transmission of HIV,
according to a World Health Organization report issued September
1, 2003.

References

1. Jackson JB, Musoke P, Fleming T, and others. Intrapartum and
neonatal single-dose nevirapine compared with zidovudine for
prevention of mother-to-child transmission of HIV-1 in Kampala,
Uganda: 18-month follow-up of the HIVNET 012 randomized trial.
THE LANCET. September 13, 2003; issue 362, number 9387, pages
859-67. [Note: This article and the accompanying editorial below
are available free to non-subscribers at
http://www.thelancet.com -- free registration is required.]

2. Beckerman KP. Long-term findings of HIVNET 012: The next
steps. THE LANCET. September 13, 2003; pages 842-843.


***** Treatment Interruption: Study Found Poor Result for Highly
Treated, Highly Resistant Patients

by John S. James

Patients whose antiretroviral treatment was no longer working
well due to extensive drug resistance were randomly assigned to
two different groups. In one, the control group, they changed
their treatment immediately to a new antiretroviral regimen
devised by their doctor with the help of viral resistance
testing. In the other, the treatment-interruption group,
patients also changed their treatment based on resistance
testing, but first they went off all antiretrovirals for four
months. The idea was to see if the virus would partly revert to
more drug-sensitive strains during the treatment interruption,
in the hope that the drugs would work better later when they
were restarted.

The virus did tend to revert to more drug-susceptible strains in
two thirds of the treatment-interruption patients. However those
patients still did worse over all. While the two groups had the
same number of deaths (8 in each), the treatment-interruption
group had more cases of disease progression -- defined as the
first occurrence of a new AIDS-defining condition in that
patient. At just under one year, the total number of cases of
death or disease progression (the primary endpoint this study
was set up to look for) was 22 of the 138 patients in the
treatment-interruption group, vs. 12 of 132 patients in the
control group that did not interrupt treatment. Only 2% of the
patients were lost to follow-up during this time.

In this trial the treatment interruption group had a CD4 count
about 85 cells lower than the control group while treatment was
discontinued, and a viral load 1.2 logs higher (about 16 times
higher).

This study was conducted by the CPCRA -- the Terry Beirn
Community Programs for Clinical Research on AIDS. This group has
very good patient follow-up, in part because patients are
studied scientifically during the course of their regular
medical care, instead of entering into a separate clinical
trial. For example, in this study patients in both groups were
given a regimen prescribed for them by their doctor, which could
be changed if needed at any time -- instead of having a standard
regimen specified in a research protocol, which usually allows
limited changes or none unless the patient leaves the study.

Comment

Even when a patient's virus does become more drug sensitive on
the whole, plenty of resistant virus is still there. Today's
resistance tests cannot detect low levels of any particular
strain. And even if there were no viral copies, the DNA in some
of the body's infected cells still contains the information,
like a library of all viral strains the patient ever had. So
when the drugs are started up again the susceptible virus may be
suppressed better at first, but usually it does not take long
for the resistant virus to come back.

Treating patients who are already resistant to most or all
available HIV drugs remains difficult and controversial, with
trade-offs between HIV progression, new resistance development,
and drug toxicity. New drugs are being developed with different
resistance patterns, and often the question is what to do now
while waiting for enough good drugs to put together a viable
suppressive regimen.

In any case this negative result should not prejudice people
against clinical trials of other kinds of intermittent
antiretroviral treatment, with very different patients,
procedures, and goals.

References

1. Lawrence J, Mayers DL, Hullsiek KH and others. Structured
treatment interruption in patients with multidrug-resistant
human immunodeficiency virus. NEW ENGLAND JOURNAL OF MEDICINE
August 28, 2003; volume 349, number 9, pages 837-846.


***** New Guidelines for Avoiding Heart Disease by Managing High
Cholesterol, Triglycerides, or Related Problems in HIV

by John S. James

On September 1, 2003, the Infectious Disease Society of America
(IDSA) released new guidelines for treating dyslipidemia (blood
fat and some related disorders) in persons with HIV. These
guidelines were prepared by a team of clinical scientists on the
Cardiovascular Subcommittee of the AIDS Clinical Trials Group
(ACTG), who updated preliminary recommendations published in
2000. These guidelines also reflect the updated cholesterol
guidelines for the general public, which were published in 2001.
The result is an authoritative (for 2003) and practical document
filled with useful suggestions and advice. The new guidelines,
11 pages of text plus 147 references, were written mainly for
physicians.

From the executive summary:

"We recommend that HIV-infected adults undergo evaluation and
treatment on the basis of NCEP ATP III guidelines [National
Cholesterol Education Project -- Adult Treatment Panel III] for
dyslipidemia, with particular attention to potential drug
interactions with antiretroviral agents and maintenance of
virologic control of HIV infection. When drugs become necessary,
we recommend as initial therapy pravastatin or atorvastatin for
elevated low-density lipoprotein cholesterol levels and
gemfibrozil or fenofibrate when triglyceride concentrations
exceed 500 mg/dL."

Basically these guidelines apply the NCEP standards for reducing
cardiovascular [heart and blood-vessel] disease risk for the
general public, to people with HIV. There are a number of HIV-
specific considerations, for example avoiding interactions of
lipid-lowering drugs with antiretrovirals. Perhaps even more
than in the general population, lifestyle changes such as diet
and exercise (and of course quitting smoking) are recommended
before lipid-lowering drugs, except in urgent cases.

The new guidelines review the following topics:
* Evidence that certain antiretrovirals cause more lipid
problems than others;
* Possibilities of switching antiretrovirals;
* Studies of the risk of cardiovascular disease in persons with
HIV, using the NCEP to help decide about lifestyle changes and
lipid-lowering drugs;
* Therapeutic use of niacin to help correct cholesterol levels,
or fish oils to reduce triglycerides, which may be tried in some
cases;
* When to refer a patient to an expert in treating dyslipidemia
in persons with HIV;
* Drug interactions, including certain lipid-lowering drugs to
avoid because they can interact dangerously with
antiretrovirals.

The guidelines were published in CLINICAL INFECTIOUS DISEASES,
September 1, pages 613-627. They are also available at the Web
site of NATAP, the National AIDS Treatment Advocacy Project,
http://www.natap.org/2003/sept/Guidelines.htm


***** 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
Reader Services: Allison Dinsmore


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 18 times per year, 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 215-546-3776:
* 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 2003 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
www.aidsnews.org