Scientists Seek Remedies
For AIDS-Injured Systems
By MICHAEL WALDHOLZ
Staff Reporter of THE WALL STREET JOURNAL
GENEVA -- Can the body's vital germ-fighting
defenses, once overpowered by the AIDS virus, ever be
revived enough to allow patients to live long and robust
lives without taking daily doses of the powerful but
cumbersome AIDS drug cocktails?
That was one of the principal questions asked all last
week at the 12th World AIDS Conference here. A
group of university and pharmaceuticals-industry
scientists believe the answer is yes. In a series of
surprising studies, some of which were presented at the
conference's last day on Friday, researchers reported
several experiments already suggesting that some
patients may someday be successfully weaned from their
life-saving drugs.
If this occurs, even in a handful of people, it will mean
that researchers have finally figured out ways to rebuild
an AIDS-ravaged immune system, something most
scientists thought was impossible just a few months ago.
"It's clear from the presentations here that some kind of
immune therapy, some kind of immune stimulation is
possible now," said Robert Gallo, director of the
Institute of Human Virology, Baltimore, and
co-discoverer of HIV, the AIDS virus.
Complex, Lifetime Drug Therapies
It is important that HIV-crippled immune systems be
restored, researchers said last week, because a lifetime
reliance on daily doses of complex drug therapies is a
burden few people appear able to take on. That is
especially true for those in low-income areas, most
particularly in developing nations where 90% of the 30
million people in the world infected with HIV live. Also,
new research is showing that the two-year old drug
cocktails that have worked so well in putting AIDS
patients into remission can cause troubling side effects
after long-term use.
Moreover, evidence presented at the conference shows
that dangerous drug-resistant strains arise when people
don't meticulously follow their daily regimen, which can
require three or four different medicines and 10 to 20
pills. Finally, there is little expectation that an effective
vaccine is anywhere in sight, meaning that prevention and
drug therapy will be the best hope against the epidemic
for many years to come.
Specifically, scientists presented data hinting that
salvaging a critical component of the immune system may
allow HIV-infected people to stave off illness or death
on their own without continued reliance on drug therapy.
These experiments involved attacking the virus within
days of an infection, using a vaccine created by vaccine
pioneer Jonas Salk that was discarded years ago as
ineffective, or by adding a controversial 40-year-old
cancer drug to the current list of 11 drugs used in
combination in the HIV-fighting drug cocktails.
'Long-Term Nonprogressors'
The central clue driving these intriguing strategies comes
from studies of certain people -- "long-term
nonprogressors" -- who have been able to fend off the
virus for as long as 10 or 15 years without serious
illness. In these people, although they are infected and
show evidence of the virus, their immune systems appear
able on their own to keep HIV in check.
In reports presented by Bruce Walker of Massachusetts
General Hospital and Fred Valentine of New York
University Medical Center, researchers showed that the
longterm nonprogressors' immune systems contained
white blood cells that are able to specifically alert
disease-fighting cells to the presence of HIV. In many
HIV patients, these so-called helper T-cells are targeted
and destroyed by the virus soon after infection. But Dr.
Walker showed that the helper cells circulating in the
blood of long-term survivors are able to constantly signal
other "killer T-cells" that can hunt down and assassinate
the virus before it can infect more cells. HIV-infected
people whose virus levels rise and become sick don't
have these helper cells anymore.
Treating Patients Early
Dr. Walker showed "patients treated very early [with
combination drug therapy] retain their crucial helper
cells." If treated within weeks of infection, he suggested,
the salvaging of the helper cells may allow patients to
someday end their drug therapy and allow the immune
system on its own to keep the virus at bay.
But, of course, such aggressive early treatment isn't
always feasible.
So several researchers, including Dr. Valentine,
suggested that one way around this is to revive helper
cells by reintroducing the immune system to a weakened
version of the HIV. This could be accomplished, he
suggested, by use of a vaccine developed in the
mid-1980s by Dr. Salk, the late polio-vaccine
developer. The vaccine, called Remune, is still being
developed by Immune Response Co. of Carlsbad, Calif.
In studies presented by Dr. Valentine and others,
researchers showed that patients on combination drug
therapy who received a shot of Remune once every
three months showed strong evidence of a re-emergence
of the helper cells. Compared with a group of patients
who weren't on Remune, those receiving Remune had
"astronomical" levels of the HIV-fighting helper cells, Dr.
Valentine said.
Remune is an agent that contains only proteins inside the
core of HIV, and not its outer envelope. Scientists think
that with virus levels reduced significantly by treatment
with the combination drug therapy, the immune system
can create helper cells once it sees the HIV proteins
contained in Remune. "It's an intriguing idea because
what they are trying to do is re-educate the immune
system to create components killed off by the first wave
of virus," said John Mellors, a University of Pittsburgh
scientist.
Immune Response, in a collaboration with Agouron
Pharmaceuticals Inc. of La Jolla, Calif., is testing
subjects to determine if the addition of Remune can not
only stimulate the immune system but also keep patients
healthier. Results won't be produced until sometime next
year.
"The [Remune] idea is very interesting and certainly
worth a try," said Martin Delaney, an activist with
Project Inform of San Francisco. "But there's been a lot
of Wall Street hype over Remune. It's not the only
vaccine out there that might work in this way, especially
in patients whose virus levels are being subdued by drug
therapy."
Finally, a research team led by Franco Lori of
Georgetown University showed that adding an old
cancer drug, called hydroxyurea, to a combination of
drugs appears also to stimulate the HIV-targeting helper
cells. The drug apparently works synergistically with
Bristol-Myers Squibb Co.'s antiviral drug called DDI,
also known as Videx, and Bristol-Myers is conducting
large clinical trials to determine if the new combinations
can revive the immune system enough to allow some
people to consider terminating drug therapy.
"We, of course, would leave [termination] up to the
patients," Dr. Lori said. "But if some with the [stimulated
helper cells] want to take that step, we will follow them
very, very closely."
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