Long-Term Survival Gains Renewed Interest at Berlin Conference

Even without a cure, a certain number of individuals remain
healthy for a decade or more after infection with HIV. Some have
normal T-helper counts while others may survive even with
drastically reduced T-helper cell counts. The individual
variation in response to HIV is a promising field to research.
Studying the reasons for successful immune response to HIV could
lead to new therapies for people with HIV whose health is
declining.

This June's International Conference on AIDS [see Conference
overview, below] will focus new attention on the factors that
make for long-term survival. The four panels the Conference is
organizing on the subject will discuss it on a variety of levels,
from the molecular influences to the social ones. Reflecting the
International Conferences' habitual tone, the most prominently
scheduled of the four panels examines the biochemistry of long-
term resistance to HIV. The session's chairman, Jay Levy, M. D.,
of the University of California San Francisco, is one
investigator who has been following a group of long-term
survivors since the mid-eighties. He gave a lecture in San
Francisco on April 28 that previewed his Berlin presentation.

One aspect of Levy's work concentrates on the immune
system's ability to control HIV after the initial acute
infection. He thinks that the crucial immune system constituent
is a particular type of cell called the cytotoxic lymphocyte.
Cytotoxic lymphocytes are white blood cells that usually search
out and kill virus-infected cells. The subgroup that interests
Dr. Levy instead secretes a chemical (a "cytokine") that
suppresses HIV replication within infected cells. A decrease in
the effectiveness of these lymphocytes allows HIV to escape
immune surveillance, and as HIV replicates, a virulent, AIDS-
triggering strain eventually evolves. Levy has been trying to
identify the unknown cytokine since 1986 in the hope of using it
as a treatment. He thinks he may finally be able to reveal its
nature in Berlin.

Another panel will examine "markers of nonprogression of
disease." A number of researchers are studying long-term
survivors as part of "natural history" studies that trace the
progress of HIV infection. Susan Buchbinder, M. D., of San
Francisco Department of Public Health AIDS Office will chair this
workshop. She also coordinates the San Francisco City Clinic
Cohort. Now used for following the AIDS epidemic, this cohort
goes back to the late seventies, when its members were recruited
for a hepatitis B vaccine trial. It contains some of the longest
known survivors of HIV. Dr. Buchbinder reports that her study
has been a fertile source of blood specimens for researchers who
are looking at individual genetic differences, immune cell
activity and viral strain characteristics for leads as to what
predicts nonprogression.

One of the presenters in this workshop is Haynes Sheppard,
Ph.D. He commented, "We all hoped that there would be definite
signs, but there seem to be multiple types of nonprogression. A
number of different things can protect you: good immune response,
nonaggressive virus, or low immune activation. When all are bad,
that's when you get rapid progression."

The cellular aspects of disease resistance covered in these
two sessions are not necessarily of direct interest for people
with HIV. Aldyn McKean, a long-term survivor and member of ACT
UP/New York, told AIDS TREATMENT NEWS, "I am much more interested
in the things I can control myself than finding out that the
reason I'm alive is because of a certain genetic makeup or a less
virulent virus."

McKean is co-chairing a roundtable discussion on the
psychosocial elements involved in long-term survival. Most
long-term survivors recommend specific practices that seem to
help them. The measures are quite diverse and include nutrition,
avoiding alcohol and tobacco, exercise, stress management and
other types of coping skills, active social and sex life, a good
working relationship with a doctor, and careful preventive
measures against infection with other diseases.

The panel's purpose is to examine what can be applied from
survivors' experience to the care and support of people with HIV
or AIDS. Three of the speakers will be long-term survivors,
another is a clinical psychologist, and two are physicians from
developing countries. The multicultural perspective that the
non-U. S. residents bring to the subject of survival will
contribute fresh insights as to how different environments and
types of care influence survival.

The fourth session will further enable conference attendees
to apply the lessons of long-term survival to their daily lives.
Participants from the first three panels will join together in a
"meet the experts" event that will discuss questions raised by
the audience. "I have a sense that people will be interested in
how long-term survival differs across regions, how access to care
affects survival, the effect of pregnancy, and what personal
suggestions individuals have," said Nancy Hessol, who is chairing
this fourth event.

Comment

Activists at last year's International Conference on AIDS in
Amsterdam denounced the lack of emphasis on long-term survival
research. They called for more concentration on long-term
survival this year at the conference in Berlin.

Aldyn McKean and others from ACT UP/New York and ACT
UP/Europe negotiated extensively with the organizers of this
year's conference. McKean wants the Berlin Conference to be a
prelude to more intensive study of long-term survival. He said,
"So far, small studies have occurred within already established
cohorts, but no one has ever put together a large enough group to
analyze variable combinations of multiple factors related to
survival. I would like to see thorough interviews of thousands
of people."

The idea of studying what makes people healthy as well as
what makes them sick might seem logical to some. But, in fact,
last year was a frustrating one for studying successful
resistance to HIV. The federal government shifted money that
previously supported studies on the course of HIV infection to
surveys designed to test the feasibility of large-scale vaccine
trials. The San Francisco Men's Health Study, a source of data
and funds for Drs. Levy and Sheppard's research, was canceled
completely, and work on the San Francisco City Clinic cohort was
curtailed.

At the same time, the immediate needs of people with HIV has
created pressure in the opposite direction. Susan Buchbinder
reports that her group's historic series of blood samples has
attracted collaborators from other institutions. These
researchers have succeeded in finding funding for investigating
signs of nonprogression. And discussions are continuing with the
National Institutes of Health (NIH) to save at least some portion
of the San Francisco Men's Health Study, including the follow-up
on long-term survivors.

NIH scientists are also talking about setting up a national
registry of long-term survivors, according to McKean and
Buchbinder. This would be a first step to the comprehensive
surveys that McKean envisions.

[Note: Dave Gilden plans to attend the Berlin meetings on
long-term survivors and review them for AIDS TREATMENT
NEWS.]