AIDS TREATMENT NEWS Issue #368, July 13, 2001
phone 800-TREAT-1-2, or 215-546-3776

CONTENTS

** Buenos Aires Conference on Treatment and Research: Web
Reports Available
A new AIDS conference attracted 3,000 scientists to Buenos
Aires, Argentina, and featured over 700 presentations --
unusually large participation for a meeting's first year.
This basic and clinical scientific research conference will
happen every odd-numbered year, when the international AIDS
conference is not held. We list some of the major topic
areas, and provide Web addresses for conference reports and
abstracts of the presentations.

** AIDS Research Today: 20 Views
One of the first organizations to conduct community-based
AIDS research asked researchers, physicians, and community
members to look at the current status and direction of AIDS
research and write a short article for publication. Twenty
responses appear in the current CRIA Update, which is
available either online or by mail.

** Africa: Interview with South African High Court Justice
Edwin Cameron
Justice Edwin Cameron of the South African High Court has
become a leading advocate for AIDS treatment and other
medical care in Africa. AIDS TREATMENT NEWS interviewed
Justice Cameron during his recent visit to San Francisco.

** Women's HIV Treatment Issues: Course for Medical
Professionals, July 26-27
A two-day course at Johns Hopkins will help physicians and
other medical professional treat HIV infection in women.

** HIV Resistance Meeting Web Reports
Where to find information from last month's meeting on HIV
resistance, which took place June 4-8 in Scottsdale,
Arizona.


***** Buenos Aires Conference on Treatment and Research:
Web Reports Available

by John S. James

A new scientific conference created by the International
AIDS Society (IAS) took place July 8-11 in Buenos Aires.
Even before the first meeting, the 1st IAS Conference on
Pathogenesis and Treatment had emerged as an important
conference, with about 3,000 scientists attending and 748
scientific presentations (out of about 1,000 submitted);
you can read abstracts of the presentations through the Web
links below. This conference will occur every two years,
during the odd numbered years when there is no
international AIDS conference.

The IAS created the new meeting to focus mainly on basic
and clinical science and the interaction between them --
including new treatments, vaccines, studies of
pathogenesis, and how research can contribute to making
good prevention, treatment and care available to the
approximately 90% of persons with HIV who currently do not
have access because they live in poor countries. The
scheduled keynote and plenary speakers were:

David Ho: Learning Basic Science from Clinical Trials

Julio Montaner: Current Controversies in Antiretroviral
Treatment

Stefano Vella: Fostering Access to HIV Treatment

Anthony Fauci: Immunopathogenesis of HIV Disease: Host
Factors in Pathogenesis of HIV Disease: Implications for
Therapeutic Strategies

Francoise Barre-Sinoussi: HIV: Twenty Years After the
Discovery of the AIDS Epidemic

Margaret Johnston: Virologic and Immunologic Concepts in
Vaccine Design

Brigitte Autran: Immune Reconstitution: Translating
Immunologic Knowledge into Therapy

Eric Hunter: The Next Target in Therapy: Viral Entry

Ashley Haase: Virologic and Immunologic Concepts on HIV
Transmission

David Cooper: Antiretroviral Therapy Toxicity: The Second
Round, Beyond Lipodystrophy

John Mellors: Resistance: From Molecular Basis to Clinical
Research

In addition, the U.S. National Institutes of Health
organized a one-day meeting the day before the conference
on "Formulating a Comprehensive HIV/AIDS Research Agenda in
Resource-Poor Setting."

AIDS TREATMENT NEWS did not attend this meeting. In future
issues we may summarize some of the presentations.
Meanwhile, extensive reports are available on the Web.

Web Access

The IAS has named Medscape as the official provider of
online conference coverage for this meeting. The Medscape
site for this conference can be reached through a link on
the Medscape home page, http://www.medscape.com

The official Conference site, which has background
information on the conference, is:
http://www.aids2001ias.org

You can search and read the abstracts of the conference by
reaching a search page through the IAS home page:
http://www.ias.se

(At this time the search function is confusing. You do
*not* need to log in with a user name and password in order
to search or read these conference abstracts. We have not
yet been able to do an 'and' search (it does an 'or'
instead) -- but with fewer than a thousand abstracts, one
can live with that. So far we have not found a link from
the Buenos Aires conference page, only from the IAS home
page -- nor have we found a link to instructions for more
advanced searches. We hope these glitches will be
corrected.)

Other Web sites with extensive coverage of this meeting
include:
http://www.thebody.com/confs/ias2001/ias2001.html
http://www.hivandhepatitis.com/2001conf/ias/main.html


***** AIDS Research Today: 20 Views

by John S. James

Twenty commentaries on the current status of AIDS research,
by "researchers, clinicians, and community members from
varying disciplines, experience and backgrounds" appear in
the Summer 2001 issue of CRIA Update, published by the
Community Research Initiative on AIDS. These brief
summaries offer diverse and informed views of what is
happening today in AIDS research -- and what may happen
over the next several years.

You can find these summaries at http://www.criany.org, or
mail a request to: CRIA, 230 West 38th St., 7th floor, New
York, NY 10018 (ask for the AIDS research issue).

Comment on Research

One idea largely missing from these commentaries (including
our own) is the possibility of a treatment breakthrough --
and the question of how to organize research to facilitate
a major, unexpected advance.

For example, one possible area for such a breakthrough
could be a treatment to disrupt the process by which, in
most patients, HIV eventually turns off the immune system's
original ability to control it well (a possibility
discussed in the CRIA Update by Sean R. Hosein of CATIE,
the Canadian AIDS Treatment Information Exchange, on
excessive levels of IL-10 in HIV disease, and the
possibility of treatments to lower them). Such an immune-
based treatment could work in both developed and developing
countries (where it might not need to wait for
antiretroviral combinations to become available).

Looking for a breakthrough -- a treatment good enough to
be, in effect, approved by acclamation -- means we would
not have to wait to solve the problem of immune-based
surrogate markers, which will probably take years (and may
be essentially unsolvable, if an effective immune-based
treatment must first be proven by clinical endpoints before
a surrogate marker can be established). In the IL-10
example, a monoclonal antibody to reduce IL-10 might
provide a proof of principle. If it clearly worked (for
example, by greatly lowering viral load or reducing the
need for antiretrovirals), then it would not be hard to
organize a major effort to find simpler or even natural
treatments to do so.

The big problem here would be the legal obstacles created
by a clinical-trial system designed for big-company drug
development. For example, the right kind of trial might be
in one patient, looking for an efficacy result even from
the first human volunteer, with no attempt to prove
efficacy first in animals.

The existing rules serve two purposes -- to protect the
public from unethical corporate experimentation, and to
protect the same corporations from competition by making it
almost impossible for anyone else to finance the whole
drug-development process. Of course, if anyone could show
truly convincing data, ways could be found to move fast.
The problem is getting permission to do the earliest proof-
of-principle human studies -- without entanglement in the
gold-plated clinical trial system which already has its own
mindset, investments, pipeline, and calendar in place, and
naturally resists encroachment on its well-manicured turf.

So we continue to fight an epidemic with rules and
procedures designed for routine, non-emergency research and
development.


***** Africa: Interview with South African High Court
Justice Edwin Cameron

by Bruce Mirken

Few moments in the history of the AIDS epidemic have been
as pivotal as the speech South African High Court Justice
Edwin Cameron gave one year ago at the International AIDS
Conference in Durban, South Africa. In a talk that SCIENCE
magazine writer Jon Cohen recently called "one of the most
remarkable acts of activism I've seen in 12 years of
covering AIDS," Cameron told of how he grew ill with AIDS
in 1997, a dozen years after becoming HIV positive, and his
near-miraculous return to health on combination therapy.
"Amidst the poverty of Africa, I stand before you because I
am able to purchase health and vigor," he told the hushed
audience. "I am here because I can afford to pay for life
itself."

He compared those who sit back and allow the world's poor
to die for lack of access to HIV/AIDS treatment to those
who passively allowed the evils of Nazi Germany and South
African apartheid to unfold. The speech crystallized
sentiment in favor of providing treatment in impoverished
nations, leading to a variety of proposals, from drug
company price cuts to U.N. Secretary General Kofi Annan's
proposed international AIDS fund.

A year later Cameron is still acting as a conscience of a
world that is too willing to let poor people die. AIDS
TREATMENT NEWS spoke to him during a visit to San Francisco
June 19.

* * *

ATN: A year has passed since your Durban speech. How has
the response been--in action, not just rhetoric?

CAMERON: There are two major changes. One is the change at
the level of rhetoric, and one must never underestimate the
importance of rhetoric. The Durban conference changed the
discourse about drug access. Up to Durban it had been
accepted that we lived in a globalized world in which drug
pricing was a given. Durban changed that irrevocably.
Durban cast a moral judgment on drug companies' prices.

The rhetoric of drug company pricing was vital, and that
rhetoric has changed. Supplanting it has been an
international consensus that drug treatment ought to be
made available in Africa--a consensus shared by almost
everyone except the South African government, I might say.
Our minister of health on the fifth of June reiterated that
she's not providing drugs in the public sector.

The second change, of course, has been at the level of drug
pricing, which has been dramatic. Some combination
therapies have come down in price by 80 percent. Two nukes
and one NNRTI are now available for $100 a month--which is
still out of reach of 90 percent of Africans but is no
longer out of reach of 99 percent.

ATN: In recent months there has been some pulling back from
that consensus, more voices saying, "Well, maybe we really
can't do this, maybe prevention is more important," etc.

CAMERON: First of all, the treatment/prevention dichotomy
is entirely false, because treatment offers the most
persuasive way of making prevention work--at a
physiological level, a psychological level, a social level.
It's a false proposition to suggest that treatment is an
area of concentration neglecting prevention.

With regard to your question about pulling back, I don't
think one should underestimate the issues. There are real
behavioral and institutional issues [in providing
treatment]. Realistic approaches don't neglect those. The
Harvard Declaration--despite very considerable conceptual
flaws, and there are huge conceptual flaws in it--is a
visionary breakthrough because it actually addresses in a
hard-headed way the practicalities of treatment access.

You may be right that there's been a pulling back, but no
one ever said that this was going to be easy. Every single
argument that the do-nothing camp advances doesn't
withstand scrutiny. In fact, the infrastructural
initiatives that drug access will require will assist
health care delivery in regard to other diseases like
malaria and tuberculosis. Certainly it's going to take some
infrastructural initiatives in Africa, but once they're up
and running they're going to alleviate other pressures.

ATN: What about the widely-quoted comments by USAID head
Andrew Natsios arguing that drug treatment is impractical
because most Africans "don't know what Western time is...
and if you say one o'clock in the afternoon, they don't
know what you are talking about"?

CAMERON: As a legitimization of inaction, it's appalling.
It's almost as though it's a cheap target because he makes
Africa sound like a Bongo-Bongoland, and that's an insult
to Africans. The same rhetoric was used 40 years ago to
justify not giving Africans the vote--the same rhetoric of
incompetence and lack of sophistication. The same rhetoric
was used not only by white colonialists but by black
African dictators to justify denying African people
fundamental rights.

The real point is that there are issues--behavioral issues
of compliance, issues of infrastructure and delivery. What
I want to focus on when someone says foolish things like
that is how do we address the real issues, not how do we
counter misdirected rhetoric.

ATN: What's your impression of the U.S. government's role?

CAMERON: I think the [Secretary of State Colin] Powell trip
to Africa in May had a very productive resonance. It
actively gave a sense of a Secretary of State who was
concerned and was engaged. I know that he's been criticized
as not following through on rhetoric, but the substantive
message of the trip was the Secretary of State at least--a
very highly, highly placed official in the administration--
wants to be engaged. He appeared to be personally moved by
the extent of AIDS. And what he said--and again, never
underestimate the importance of rhetoric--he said that
there is no bigger war, with thirty million lives at stake
this is the biggest war on the globe at the moment

My sense is that the administration might be able to
deliver more than people expect it to.

ATN: What about the U.N.?

CAMERON: Kofi Annan is the right person to head this. His
global fund is a breakthrough. Again, like the Harvard
statement, it creates a vision which requires
implementation. But a year ago we even lacked the vision.
Precedent steps to action are changing the rhetoric,
creating the vision and making plans. And setting in place
the preconditions, one of the preconditions being
substantial reductions in pricing. We need more reductions,
but at least there have been those changes since a year
ago.

ATN: Is it worrisome to you that there hasn't exactly been
a rush to donate billions of dollars to Kofi Annan's AIDS
fund?

CAMERON: Yes, of course it worries me. I would like that
pledge to be made unreservedly and immediately by the G-7
or G-8 now, today. Once the money is there, the real issues
of implementation loom enormous--like democracy in Africa,
like the coming of independence presented real challenges
to us in how we crafted our constitutions, how we permitted
freedom of association and freedom of expression.

We're going to have to start realistically. Botswana, a
nation of 1.6 million, with the highest percentage
prevalence of any nation in the world, over 30 percent, has
undertaken to provide antiretroviral treatment in the
public sector. It will offer a good model, because it's an
ethnically homogeneous society with a high per capita
national wealth and strong governmental commitment.

What I'm saying is the funding is essential and yes, it
must be provided immediately--and then the work can begin.

ATN: How significant, in terms of day-to-day efforts to
deal with AIDS in South Africa, has President Mbeki's
interest in the denialists been?

CAMERON: [After a long pause and a half-suppressed
chuckle]: It's a question I always welcome, especially when
a tape recorder's running. Let me be diplomatic. The year
during which President Mbeki openly gave sustenance to
denialist beliefs was a year of horror--for AIDS
prevention, for AIDS implementation, for everything. It was
a year of nightmare.

In October of last year the President accepted advice that
he back off on the issue publicly. In April this year he
gave an interview in which he said that he wouldn't have an
HIV test because it would merely be giving substance to
what he called "one particular paradigm." I believe that
it's a grievous tragedy that we are still approaching the
matter as though these are debatable paradigms.

The underlying anxiety that everyone has is whether the
President's own ambivalence on the paradigm that HIV causes
AIDS is leading the government's continued dithering on
drug provision. The minister of health, on the fifth of
June in Parliament, on the very anniversary of the first
MMWR report on AIDS, reasserted her government's refusal to
provide antiretroviral treatment. She then said--very
significant--I wish to assure members of parliament that
our position is "not ideological."

It remains to be seen whether the President's ideological
position on whether HIV causes AIDS is in fact not at the
root of the government's position. If it is, the words of
Professor William Makgoba, who is the President of our
Medical Research Council--he gave the James Hill Memorial
Lecture to the National Institutes of Health in April this
year--he said that if dissident views have impeded our
treatment of AIDS, "history may say we have collaborated in
the greatest genocide of our time." I cannot do more than
quote those words.

ATN: Is that what's behind the South African government's
reluctance on treatment, even on things like mother-to-
child transmission? Or is something else involved?

CAMERON: Like the free provision of nevirapine by
Boehringer-Ingelheim--an offer made a year ago to South
Africa, still not accepted. No, I can't think of any other
issues related to that. The minister of health says,
"toxicity." The birth of 200 babies with HIV every day is a
toxic issue that outclasses on any scale the doubts about
the toxicity of nevirapine, which could reduce those 200
births every day in South Africa to 100.

ATN: American AIDS denialists say that there is no AIDS
epidemic in Africa. They admit some people are ill and even
dying, but say they're dying from endemic, poverty-related
diseases that have plagued Africans for generations.

CAMERON: It's demonstrable, pernicious, willful, distorted
untruthfulness. What is significant about our death rate in
South Africa is not just that it's increased--the
dissidents, particularly [Charles] Geshekter, explain this
on the basis that the figures for South Africa before 1994
excluded the bantustans. But that's not the only way that
our death rate figures have changed. The shape of the
figures has changed. Women in mid-life are now dying more
than men are dying. Women in their 20s and 30s are dying in
a way that women nowhere else in the world are dying--
before men.

This is an epidemic. It is an infectious agent. It is
called HIV. It leads to a syndrome of immune dysfunction
that leads to a terrible and lingering death. And most
importantly it is avoidable by virologically specific
treatments. And to deny that there is an epidemic in South
Africa is *precisely* the same as denying that five and a
half million Jews died in the Holocaust in the second world
war. It is a denial of the same epic and the same
pernicious, ideologically loaded proportions.

ATN: How important a role have activists from the U.S. and
other developed countries played in efforts to bring
HIV/AIDS treatment to Africa?

CAMERON: Central. Pivotal. Critical. The change in rhetoric
and the reduction in drug prices were the direct
consequence of principled, strategic intervention by angry
activists. The AIDS epidemic has reshaped the way we think
about ourselves as humans. I don't think it's too dramatic
or pretentious to say that. 20 years ago we thought that
we'd conquered disease, there was a medical model of human
well-being that was certainly entrenched. AIDS has shaken
that.

AIDS activists in America in the 1980s changed the nature
of the doctor-patient relationship, the nature of the
research community's relationship to the patient community.
It changed the way that the gay and lesbian community
related to the larger society. And activists are still
leading the debate. They are changing the way in which
people permit themselves to see other people.

ATN: What can people in the U.S. or other places outside of
Africa do now?

CAMERON: Three things, which all sound quite grandiose, but
we've got to start somewhere: Pressure on the drug
companies to permit generic production of patented
medicines. Secondly, pressure on governments to make the
funds available. The question with the funds is not whether
it's affordable, the question is one of will. It really is.
$7-$9 billion a year--which is for all Kofi Annan's
associated costs, not just for AIDS--is not a great amount
on any metric.

And thirdly, individual initiatives are also very
important. This is something that is underestimated. There
is an organization called AIDS Empowerment and Treatment
International. AIDSETI has got 800 to 1,000 people on
treatment this year who wouldn't otherwise have had
treatment. It collects drugs, gets donations, makes
treatment available with monitoring, with medical
supervision, even in Africa.

What I'm saying is that there is something that everyone
can do. Every organization ought to think of partnering
with an organization in Africa. $5,000 dollars equals the
salary of one nurse for one year in South Africa. There are
organizations currently that can use recyclable drugs.

We don't only have to be grandiose in what we think we can
do. The problem also requires minute, person-to-person,
organization-to-organization responses. If we look only at
the grandiose we risk paralysis, but there's a great deal
we can do at organizational and personal levels now.

ATN: Is there anything else you'd like to add?

CAMERON: I think what AIDS asks us to do is to give people
on both sides of the First World/Third World divide a sense
of empowerment about themselves. The people in the First
World should realize that there is something they can do,
not feel a sense of paralysis or helpless guilt. And the
same in Africa, that this is a problem that we can
confront.


***** Women's HIV Treatment Issues: Course for Medical
Professionals, July 26-27

Johns Hopkins University will offer a 2-day update for
primary care providers on HIV care for women, July 26 and
27. "This course is designed to offer support to the
primary care provider in caring for HIV-positive women.
Specific clinical problems, their evaluation and
management, epidemiology and scope of HIV infection will be
discussed. Participants can expect to become more familiar
with health care issues of HIV-positive women and the
management of clinical complications."

For more information, see:
http://www.hopkins-aids.edu/educational/
events/womissues_2001/womissues_2001.html
(Note: Do not include the carriage return; you may need to
create a word-processing document, paste in the URL, edit
out the carriage return, then paste the address into your
browser.)


***** HIV Resistance Meeting Web Reports

Each summer there is a small, invitation-only International
Workshop on HIV Drug Resistance and Treatment Strategies;
this year the 5th workshop in this series was held June 4-
8, 2001 in Scottsdale, Arizona. Recently, a 9000-word
detailed technical report of this meeting, written by
leading HIV researcher Daniel R. Kuritzkes, M.D., was
published on Medscape:
http://hiv.medscape.com

This report should be read by HIV-specialist physicians and
other medical professionals; most patients will find it
difficult, but may want to scan it to look for any
information that might be relevant to their treatment.

Dr. Kuritzkes summarized the highlights "perhaps of most
immediate relevance to day-to-day clinical practice":

* Y318F is a newly recognized mutation associated with
NNRTI resistance.

* Treatment-naive patients with novel mutations at 215 are
at risk for rapid selection of resistance to zidovudine.

* Data continue to confirm that stavudine and zidovudine
are cross-resistant.

* Presence of mutations at codons 82, 54, and 10 together
with 4 additional PI resistance mutations is significantly
associated with failure of lopinavir/ritonavir.

* Ritonavir boosting of indinavir may partially overcome
indinavir resistance.

* Resistance mutations confer a loss of viral fitness
relative to wild-type, but the clinical significance of
this remains unclear.

* The CCTG 575 study failed to show a benefit from
phenotyping in guiding the selection of a salvage regimen,
except in the subgroup of patients with virus resistant to
more than 3 protease inhibitors at baseline.

* The benefits and risks of treatment interruptions are
still under investigation, but risks may include emergence
of lamivudine resistance.

* The majority of zidovudine- and abacavir-resistant
viruses remain susceptible to tenofovir, although cross-
resistance is observed in virus with multi-NRTI resistance.

* New technologies to assess resistance to entry inhibitors
such as T-20 and T-1249 are in development.

The abstracts and other reports from the meeting may be
available through
http://www.intmedpress.com (after a complicated
registration procedure).

Other reports are can be found at:
http://www.hivandhepatitis.com/2001conf/hivresis/main.html
http://www.natap.org/2001/5thresist/ndx5thresist.htm


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