WASHINGTON - For the next three years, Doug Pfaff and Rand
Snell, both sexually active gay men, will roll up their sleeves
for injections that scientists hope will protect them against
Pfaff, a 39-year-old salesman for a computer training company
from Fredericksburg, Va., and Snell, 43, a public relations
consultant from Washington, have volunteered to be guinea pigs
in the first large-scale test of an AIDS vaccine.
Both men are part of a national experiment that by next June
will involve 5,000 high-risk participants, mainly sexually
active homosexual men. Each volunteer will be inoculated seven
times over 36 months with an experimental inoculation called
AIDSVax, and all will have regular blood tests for any signs of
HIV infection they may contract through unsafe sex.
The program, managed by vaccine maker VaxGen of South San
Francisco, with help from the National Institutes of Health, is
still seeking volunteers in the gay community. About 1,000
people have signed up so far.
San Francisco will be the next large city to join the effort.
Two clinics - at the AIDS office of the Department of Public
Health and at San Francisco General Hospital - will begin
recruiting 300 volunteers sometime next month. The principal
investigators are Drs. James Kahn of San Francisco General and
Susan Buchbinder of the city Department of Public Health.
Of the 5,000 volunteers nationwide, about 3,300 will receive
the vaccine, and the remaining 1,700 will receive a placebo
consisting of a harmless mixture of sterile water and aluminum
The researchers face this dilemma: There is no way to determine
whether the vaccine is effective unless the volunteers are
exposed to the HIV virus, which causes AIDS. On the other hand,
medical ethics prevent researchers from promoting risky sexual
behavior - in fact, volunteers are warned against unsafe sex
when they sign up.
Underlying the research is the assumption that participants
will stray from the safe-sex regimen and have unsafe sex
sometime during the trial.
"They make it very clear from day one that we know what safe
sex is," said Pfaff. "But they don't want anybody necessarily
to change their behavior." Margaret McCluskey, the trial's
project director for the Washington area, stressed that the
volunteers were counseled regularly on safe sex practices. Yet,
she said, "We all know that knowledge doesn't always change
behavior. We are relying on human nature."
Both Pfaff and Snell say they practice safe sex and will
continue to do so during the trial. But Snell acknowledged
that, in the heat of the moment, some gay men opted for
unprotected sex at times.
"We all take risks," he said. "Hopefully, they are educated
risks. It's a reality that not everyone is perfect all the
Despite safe-sex counseling and the good intentions of
participants, researchers estimate that during the three-year
experiment, 1.5 percent of the placebo group will be infected
with the deadly virus each year.
At the end of the trial, researchers will compare the infection
rate of the placebo group with that of the vaccine group. If
AIDSVax is effective, the vaccine group should have a lower
"Anything under 1.5 percent, we'd be very happy about," said
"We'd have to ask, "Did the vaccine do that?'"
The expected 1.5 percent infection rate in the placebo group is
based on previous studies, by the NIH and the Centers for
Disease Control and Prevention, of gay men counseled on safe
Risks of testing
Historically, vaccines have proved to be an extremely effective
weapon against other diseases. Such once-deadly scourges as
smallpox and polio have been all but wiped out in the developed
world. Those successful vaccines were perfected in similar
clinical trials, in which one group received the vaccine - and
ended up healthy - and a control group got a placebo and ended
up contracting the disease being studied.
Before being accepted onto the trial, volunteers have to meet
*They must be sexually active with other men.
*They must be involved in a monogamous relationship with an
HIV-positive man or have had sex with three or more men during
the last year and have had anal sex during that period.
*They must be HIV negative at the outset and pass a physical
Volunteers are required to read and initial each page of a
12-page consent form that warns them that they shouldn't assume
the vaccine protects against HIV: That's what the experiment is
attempting to determine. An informational pamphlet tells
volunteers, "You will not know if you are receiving the placebo
or the study vaccine."
Although the experiment focuses on gay men, who account for the
majority of new HIV infections each year in the United States,
it also includes a small percentage of sexually active women
because they account for a growing segment of new cases. Female
volunteers must have contracted a sexually transmitted disease
sometime in their lives and have had at least two male sex
partners in the last year.
The company and the Thai government are conducting a separate
large-scale experiment in Thailand to determine the
effectiveness of the vaccine against AIDS transmitted through
intravenous drug use.
The U.S. trial is "double blind," meaning that neither the
volunteers nor the experiment's administrators, nor the
vaccine's manufacturer knows whether a volunteer is receiving
the vaccine or the placebo.
Snell decided to volunteer because of the terrible toll AIDS
has taken on the gay community. "I've had a lot of friends who
have died," he said. "I felt that the potential benefits of the
trial were significant. It's an opportunity to participate in
something that expands the basic knowledge of science."
Not 100% effective
Bioethicists worry that if the vaccine shows only partial
effectiveness, it could spark an increase in risky sexual
"When a vaccine is eventually licensed for widespread use, it
is very unlikely to be 100 percent effective," Michael Langan
and Chris Collins of the AIDS Research Institute at UC-San
Francisco wrote in "Paving the Road to an HIV Vaccine," a paper
published Dec. 1.
The experiment, a so-called Phase III human clinical trial, is
the final rung on the research ladder before the federal Food
and Drug Administration grants approval for widespread use.
Phase III experiments are designed to test the overall safety
and effectiveness of drugs that have already shown some benefit
in prior studies.
Phase I and Phase II government-approved experiments showed
earlier that AIDSVax protected chimpanzees from HIV infection
and sparked an immune system response in humans.
"The big question is: How effective is it in real-life
situations?" said Dr. Donald Francis, president of VaxGen and a
former AIDS specialist at the CDC.
Researchers already are dampening expectations.
"We know that the vaccine didn't work 100 percent in earlier
trials," said Joe Wright, a community coordinator for San
Francisco's Department of Public Health AIDS office.
A key reason is that the vaccine isn't engineered to protect
against all strains of HIV, a virus that mutates easily.
"People should see this vaccine trial as a larger process
toward a successful vaccine at some point," Wright said.
One deterrent to getting more volunteers, VaxGen's Francis
said, has been a fear that the experimental vaccine may
actually infect volunteers with HIV. Scientists stress that
that's impossible. The vaccine is derived from a synthetic
protein, not a live virus. In addition, the National Institute
of Allergy and Infectious Diseases has already conducted six
small trials on the vaccine to ensure its safety.
"There is zero chance of infection," said Francis, who himself
has been inoculated with the vaccine.
For more information on the San Francisco vaccine trials, call