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Eulogy for a
Doomed Vaccine

Eulogy for a
            Doomed Vaccine

It was bad
enough when a promising HIV vaccine’s global trial
was halted last September because the drug under study
failed to prevent infection. But it got even worse
when scientists discovered in November that in some of
its recipients the vaccine might actually have promoted
HIV infection. The twist was like a sick joke: A product
designed to protect people from HIV could instead help
them get it?

The vaccine under
study -- only the second ever to garner a critical
Phase II clinical trial -- was expected to be a major
breakthrough in the fight against HIV. Developed over
the course of a decade by drug company heavyweight
Merck & Co. and being tested in nearly 3,000 people from
North and South America, the Caribbean, and Australia, the
vaccine was designed to stimulate the body’s T
cells in order to better ward off the insatiable
virus. The previous vaccine to reach the Phase II stage had
targeted antibodies, the immune system’s other set of
defenders, but it had proved a bust in 2003. Hopes
were high that the T-cell approach would succeed.

Instead, a
midpoint analysis made public on September 21 showed
statistically comparable rates of infection for volunteers
(all HIV-negative at the start of the trial) who had
received the vaccine and those in the placebo group.
What’s more, in those vaccine recipients who
became infected with HIV, the vaccine also failed to lower
their virus levels -- another area of inquiry for
investigators. The vaccine was a loser, and there was
nothing to do but stop the three-year-old trial.

It was a
devastating denouement for anyone aware of the
stakes—experts widely believe that a vaccine,
if not a cure, is the only thing that can turn around
the runaway HIV/AIDS pandemic. But like a thriller, this
trial held one last plot surprise in store: People who had
received the vaccine were in fact becoming infected
with HIV at a higher rate than those in the placebo
group. According to the latest data available, 49 of
the 914 men who received the vaccine became infected with
the virus, while 33 of the 922 who received the
placebo tested positive. (The remaining 839 volunteers
were women, only one of whom became infected.)

Suddenly what had
been a straightforward story of loss became a vexing
mystery. Although the vaccine was made with three HIV genes,
they were synthetic -- like Xerox copies of original
documents -- so it was impossible to get infected from
the vaccine itself. That left two possible
explanations: Either vaccine recipients who contracted the
virus guessed that they had been vaccinated -- like
any legitimate scientific study, the trial was
double-blind, meaning neither subjects nor researchers
knew who received what—and, assuming they were
protected, consequently engaged in riskier behavior.
Or, more probably, the vaccine facilitated infection
in some way.

Indeed, the
leading hypothesis among investigators is that the vaccine
somehow made the immune system more susceptible to
infection. However, the increased susceptibility
appears to be limited only to those vaccine recipients
who had a pre-existing immunity to the cold virus used in
the vaccine to transport the HIV genes into the body.
For reasons that still need to be determined, that was
the group that saw an increase in HIV infection. If
you had been given the vaccine but had lower immunity to
the cold virus, your risk was likely no greater than that of
the placebo recipients.

Either way, as a
study participant, this was the last thing I wanted to
hear. I have always felt guilty for being HIV-negative. As
much as we know about safe sex, the importance of
protecting ourselves, and the ravages of AIDS,
accidents still happen -- including the accident of
birth. What if I had been born early enough to arrive in New
York City as a young man in the early 1980s, when the
virus was just beginning to circulate, incubating
among a generation of men who had no idea what was
about to befall them? Fresh-eyed and adventurous, I would
surely have died. Instead, I came to the city after
college in 2000, having never met anyone who was
positive. That difference in fates weighed heavily on me,
a kind of spiritual survivor’s guilt.

So when I learned
three years ago in the course of my work as a
journalist that an international HIV vaccine trial was
enrolling gay men and other people at “high
risk” (such as heterosexual black women) for
contracting the virus, I decided to participate. I knew it
would make a good story, but I also hoped it would
assuage my feelings of guilt. Instead of helping just
one person, as the save-a-starving-child proselytizers
constantly beseech us to do, a viable HIV vaccine could
benefit an untold number of people. It could even end the
global epidemic. Medical progress so often relies on
human guinea pigs -- it seemed like my duty to
participate.

Still, it was not
a decision I made lightly. During the initial
consultation at the trial site in a nondescript office suite
in New York City’s Union Square, one of 25
cities where the HIV Vaccine Trials Network conducted
the study, a staffer apprised me of what lay ahead.
Although the gist was simple enough -- three injections of
the vaccine over the course of six months, then
follow-up visits that would slowly dwindle before
ending 4½ years later—the details were harder to
comprehend. For one thing, I would have to give a lot of
blood, sometimes filling as many as 32 vials, which
would be sent to a lab for analysis. For someone
squeamish about needles, let alone seeing my own red liquid
outside my body, the prospect made me want to throw up.

Then there were
more practical considerations, like the fact that because
of the HIV genes that would be injected into my body, I
would turn up as positive in routine HIV screenings.
Consequently, I could be tested only at the study site
(and as part of the study, I was, on a regular basis).
If I needed to prove that I was negative for any reason --
say, to visit a country that currently bars
HIV-positive visitors, such as China -- I would have
to disclose my participation in the trial and provide
documentation. I doubted people would understand. (In fact,
they didn’t: When I would bring up the subject
in casual conversation, I realized that many people
assumed I was HIV-positive, even though by definition a
vaccine is given to those who don’t have the target
of prevention.)

But my biggest
concern, as attested to by the mounds of paperwork I
signed, was that there was no telling what could happen to
me in this unprecedented experiment. Though I was
reassured that the vaccine was innocuous, no one had
received it before, so there was no long-term
knowledge of its effects. If it worked (and I had received
it), then great—I would be biologically
protected from a most nefarious scourge. But what if
it didn’t work—or worse, had some unforeseen
negative consequences? The staffer had no answers for
me. That’s how it is on the leading edge of
science: murky and uncertain.

Yet my hand was
forced when a friend of mine, nearing 30, suddenly became
infected with HIV. Thanks to a single unsafe sexual
encounter, his life was changed forever. It was too
late to save him from infection, but maybe I could
save others -- maybe even myself.

Until this fall,
the whole experience was as smooth as could be. The
injections were akin to getting a flu shot, and the various
sums of money I collected at the end of each
appointment, between $25 and $75, were welcome pocket
change. I would leave the study site, get a Jamba Juice
around the corner, and go on with my life. I rarely thought
about the trial; it was a nonissue.

The only time it
became a problem was when I told a boyfriend about it.
Normally I didn’t disclose my participation to sex
partners, since the vaccine couldn’t affect
them, but he was different. We were in a relationship,
and I felt like he should know. So one night, in the middle
of a certain sex act, I blurted it out. “Now
you’re telling me?!” he practically
yelled. I shrugged. It seemed like an opportune time.

Being in the
trial, I even learned a valuable lesson: that my own
safe-sex regimen works. I’ve been tested more than a
dozen times since I enrolled in the study, and every
time the result has been negative. It’s
embarrassing to admit now, but I didn’t get my first
HIV test until I was 25 because I was irrationally
afraid that it would come back positive, even though I
had never engaged in unsafe behaviors. To know that I was
effectively shielding myself was tremendously reassuring.

And then, of
course, I discovered that maybe I hadn’t shielded
myself at all -- that maybe, instead, I had
inadvertently thrown myself into the lion’s
den. When a trial staffer called in November to inform me
that the vaccine might have promoted HIV infection and
that all study volunteers would be
“unblinded” so they would know what they got,
I didn’t quite understand her.
“Isn’t an HIV vaccine supposed to prevent
infection?” I asked. The staffer nervously
laughed.

It wasn’t
until the following day that the reality of what had
happened started to sink in. There, on the front page
of The Wall Street Journal’s Marketplace
section, was a story whose headline said it all:
“Canceled Vaccine May Have Boosted HIV
Risk.” I started to feel anxious. All my
initial concerns about participating in the study came
roaring back to the forefront of my mind. Had I put my
body on the line for science only to have harmed it?

I didn’t
know the answer to that yet, but the vaccine effort itself
was clearly damaged. As Anthony Fauci, the well-known
HIV researcher who directs the National Institute of
Allergy and Infectious Diseases, which provided
funding for the trial, told the Journal, the
vaccine’s failure will force the field to
“relook at everything.”

“It’s just extraordinarily disappointing to be
faced with another vaccine that is not
effective,” epidemiologist Beryl Koblin, the
principal investigator for two of the study sites in
New York City, told me recently. “Sometimes
it’s hard to find the words because of the urgency,
and that desire to be able to find a vaccine as quickly as
possible.” Indeed, at an HIV Vaccine Trials
Network conference in Seattle in November, where the
troubling results were announced, one staffer told me
she had never seen such grief.

As for the
apparent increased risk of infection, Koblin said,
“For me, personally, that is just really hard.
You never want to put people at more risk than is
already there.” But she cautions that there’s
still a “huge amount of data that needs to be
sorted through to see whether there’s a true
biological effect going on.” A special committee has
been charged with assessing the results; study
participants will also be tracked. There are lots of
factors to consider. Among the clues: People from
outside the United States or Europe tend to have a higher
prevalence of immunity to the cold virus used in the
vaccine; non-Americans in the study were also less
likely to be circumcised. What does it all mean? Only
time will tell.

From a public
relations standpoint, however, this has to be a disaster,
right? Koblin said that so far, recruitment for the various
Phase I trials she oversees -- there are more than 30
currently under way worldwide -- hasn’t been
affected, but she knows there may be problems down the
road, when volunteers are needed for a Phase II trial of a
new vaccine. One had been set to start last September,
but it was scrubbed when the Merck vaccine failed.
It’s now being redesigned, and she thinks it
could begin in another year.

“We have
to keep going,” Koblin said. “But we need to
be really careful about how we proceed.”

In December, I
went to the study site to find out whether or not I had
received the vaccine. Volunteers who had been given the
placebo would be eligible to participate in future
vaccine trials, and before my appointment, I wondered
if I would want to. I was hoping I had been given the
placebo simply because I wouldn’t be at higher risk
of contracting HIV, which would be a relief. But it
would also mean I would have to decide whether to put
my life on the line again. It seemed like a game of
Russian roulette: Spin the barrel of the gun and you could
be fine -- but maybe not.

“What do
you think you got?” Leah Strock, a nurse practitioner
and the resident clinician, asked me. Over the last
three years I had grown quite fond of Strock, a doting
big-sister type and former punk rocker who had dated
the cartoonist R. Crumb in the 1980s. I told her I
hadn’t really thought about it.
“You’d be the only one,” she said with
a laugh. (Jokes aside, all the study participants have
been very understanding about the turn of events,
Strock told me. One who learned he was at increased risk
took the news in stride, pragmatically deciding to use
condoms for every kind of sex act going forward.)

Strock was
waiting for an answer to write down on the sheet in front of
her, so I said “placebo,” which is what I was
praying for. She turned to a spreadsheet that listed
all the participants at the site, coded by numbers.
Next to my number it said “vaccine.” My
stomach turned over. “But you don’t have
the immunity to the cold virus, so you’re
fine!” Strock quickly added. My mood lurched
again. I wanted to hug her.

As happy as I
was, it also meant that, for better or worse, I could never
again participate in an HIV vaccine study. The decision was
made for me -- and I can’t say I’m
unhappy about it.

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