[Hpn] Aides vaccine trials

Thomas Cagle nh-adapt@juno.com
Tue, 24 Dec 2002 11:29:19 -0500


   From: Catherine Alfieri <calfieri@rochester.rr.com>
Subject: FW: BostonGlobe: Anticipation grows for AIDS vaccine
 
Anticipation grows for AIDS vaccine

Human trial ends; findings awaited

By Raja Mishra, Globe Staff, 12/23/2002

cientists have finished the first human trial of an AIDS vaccine, a
mammoth
$200 million, 5,400-patient effort more than a decade in the making.


Within three months, the vaccine's maker, California-based VaxGen Inc.,
will
reveal whether simple injections can protect against the world's most
feared
viral killer. Already, the Food and Drug Administration has granted the
vaccine fast-track status that would speed it through the approval
process,
if it proves effective, for public availability.

Public health researchers have long believed that only vaccines can
reverse
the global HIV epidemic infecting more than 30 million people, most in
the
developing world. This trial remains the only short-term hope: The next
large-scale vaccine trials will not be completed until around 2010.

The much-anticipated experiment unfolded in hundreds on North American
examination rooms, including some in Boston. Doctors injected gay men and
heterosexuals with numerous sex partners with a clear solution: half were
given the experimental HIV vaccine, which is designed to disrupt the
virus'
spreading mechanism. The rest received an inert placebo.

Though critics have questioned whether the vaccine is potent enough to
truly
reverse the epidemic, even pessimists say a partially effective vaccine
could save thousands of lives in the AIDS-ravaged developing world where
few
can afford treatment.

Shortly after Dec. 31, VaxGen will begin analyzing whether the vaccine
protected people against HIV, with the possibility of an announcement by
late March.

''I pray often for a vaccine, given the scope of the pandemic,'' said
Michael Duffy, executive director of the AIDS Action Committee in Boston.
''But there's been a lot of false starts since this virus was discovered.
There have been so many dashed hopes over the last 20 years.''

Beyond the trial's results, reseachers praise VaxGen and its network of
private investors, including billionaire Microsoft co-founder Paul Allen,
for mounting a complex, ethically delicate experiment that required 5,400
volunteers in the United States, Canada, and Puerto Rico to maintain
rigorous schedules of injections, checkups, and AIDS tests over several
years.

''This is a tour de force, in terms of being able to execute a complex
trial
with the proper ethical considerations,'' said Dr. Raphael Dolin, head of
Harvard Medical School's HIV vaccine unit.

The trial unfolded at 61 locations, including Site No. 004, the Fenway
Community Health center. Previous small-scale trials demonstrated that
the
vaccine was safe. No other AIDS vaccine trials have moved past this early
stage.

Next, 5,100 gay men and 300 promiscuous women, all at risk for HIV, were
recruited as volunteers. Half received the vaccine, half were given the
placebo. Neither doctor nor patient knew which was which in the
double-blind
study: the vaccine and placebo looked identical.

Doctors told volunteers that the vaccine may not work and that they might
have been injected with the placebo. Also, doctors were obligated to
advise
the high-risk patients to change their behavior, potentially causing them
to
steer clear of HIV and undermine the trial. But statistics indicate that
a
significant portion of them will ignore doctors' advice, allowing a
scientifically meaningful test of the vaccine.

''I honestly don't know what we're going to find,'' said Dr. Kenneth
Mayer,
medical research director at Fenway Community Health, where he injected
122
men with either the vaccine or placebo.

Volunteers were given seven shots over 21/2 years, interspersed with HIV
tests and detailed interviews asking, as Mayer put it, ''What did you do,
and with whom did you do it?'' questions. Still, 90 percent of those
enrolled completed the regimen and all the data - reports stacked higher
than the Statue of Liberty - were electronically sent to VaxGen
headquarters
in Brisbane, Calif.

In January, the company will reveal who got the vaccine. Then comes a
simple
question: Did the vaccine group have noticeably fewer HIV cases than the
placebo group?

VaxGen promises to release the data on the vaccine's effectiveness by
March,
an event certain to generate enormous attention. VaxGen head Dr. Don
Francis
refused to make predictions.

''You don't know the outcome until nature gives you the message,'' he
said,
adding, ''I don't think that there's any doubt, from the chimp data, that
the vaccine is effective.''

The vaccine first proved itself in primates. Chimps acquired complete
immunity against a version of the virus that the vaccine was precisely
tailored for. A second test found similar immunity against a mutated form
of
the virus; HIV has various genetic strains.

In fact, five to seven months after the results from the VaxGen trial,
the
company is scheduled to report results from the Thailand wing of the
trial,
where 2,400 intravenous drug users were given a version of the vaccine
designed to target the HIV strain prevalant in Asia and Africa.

HIV infects and kills immune cells (the cells that defend against
disease)
before the body can muster a response. The VaxGen vaccine, called
AIDSVAX,
induces the immune system to produce antibodies that attach to a protein
called gp120 on HIV's outer layer that HIV uses to grab healthy cells.
Jamming up gp120 this way will stop HIV from spreading, VaxGen scientists
believe.

But recent studies have shown that fast-mutating HIV can even change its
gp120 protein in ways that evade vaccines. Francis, however, remains
hopeful
that his vaccine will protect against some HIV strains. Even if the
vaccine
is only 30 percent effective, he argues, that may be enough to ''drive
the
epidemic into the ground.''

His hopefulness draws from mathematical studies by Dr. Ronald Gray of
Johns
Hopkins University, who calculated in 2001 that a vaccine with 50 percent
efficacy, distributed widely, could decrease HIV caseloads. Even a lower
effectiveness level would still save lives.

Francis has a large presence in AIDS research. His efforts in the early
days
of the epidemic figured prominently in Randy Shilts's best-selling book
on
AIDS, ''And the Band Played On,'' which was made into a film. He has
weathered much criticism over the vaccine trial.

''People were saying it wouldn't work, but we went ahead,'' he said.
''You
can't tell if it works unless you run a trial.''

But doubters remain: those who believe the vaccine cannot outwit HIV's
chameleon-like nature.

''I think the feeling of most of the scientific community is one of
skepticism,'' Dolin said. ''The feeling is that the likelihood of success
is
small. But the data will speak for themselves.''

But, despite low expectations, Dolin said that ''it would still be very
disappointing if the results are negative.''

A complete failure would mean that a vaccine is, at a minimum, a decade
away, when testing on the next generation of vaccines should be
completed.
By that time, 45 million more people are expected to be infected with
HIV,
mostly in the developing world. The current drug treatments, while
effective
at extending the life of patients in the West, remains too expensive for
most in Africa and Asia. Most physicians and activists have concluded
that
only a vaccine can avert humanitarian disaster.

Raja Mishra can be reached at rmishra@globe.com.

This story ran on page A1 of the Boston Globe on 12/23/2002.
 Copyright 2002 Globe Newspaper Company.

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