Is AIDS Research Back to Square One?

Editors' Note: This piece has been corrected.

It's hard to think of Anthony Fauci as a pessimist. He's headed up the National Institute of Allergy and Infectious Diseases since the beginning of the AIDS epidemic. And given how few and far between major AIDS breakthroughs come, you've got to possess some truly audacious hope to keep that gig for two decades.

Still, there was no mistaking the disappointment in his remarks to the 300 scientists he brought together in Bethesda, Maryland, this week. On the heels of one the biggest setbacks AIDS research has seen since its early years -- a failed vaccine that had promised to mark the beginning of the epidemic's end -- Fauci convened the sober meeting to rethink the whole enterprise. And after 25 years of aggressively pursuing an AIDS vaccine, the new perspective he urged upon researchers was a return to "fundamental questions." It sounded an awful lot like starting over.

Worse, it sounded like starting over with a handicap. AIDS research hasn't been spared the budget cuts that have hit the National Institutes of Health throughout the Bush years. And even as Fauci tried to reassure the gathering that there'd be enough money to re-prime the research pump, he conceded he'd never seen times so tight. A scientist to the last, Fauci called it "an unprecedented phenomenon."

It's also a stunningly fast reversal of fortune. As recently as last summer, even the most sober observers suspected the vaccine sleuths were on the cusp of a world-changing breakthrough for AIDS, one on par with the 1996 unveiling of multidrug antiretroviral therapy, which slammed the breaks on AIDS deaths in the developed world.

A working vaccine is, as University of California at San Francisco's Werner Greene put it at this week's meeting, the "holy grail" of AIDS research -- and rightly so. HIV is spread by intimate, utterly natural acts of vulnerability. Without a vaccine, actually stopping that spread seems an insurmountable challenge. That's particularly true in places like sub-Saharan Africa, where HIV is so prevalent as to be a part of everyday life. And it's been only through vaccines that we've conquered many of history's intransigent viral diseases -- polio, small pox, measles.

The problem with HIV is that we still know so little about it, and what we know we can't do much to affect. Typically, vaccines work by stimulating your body's own production of antibodies to fight a given infection. You avoid the flu by teaching your body to fight off each season's likely strands in advance. But the wily HIV is infamous for the speed at which it mutates -- that's part of what makes it so hard to treat once you're infected -- and no vaccine has been able to keep pace. Moreover, it attacks the very immune cells a vaccine depends upon to work.

But a few years ago a novel solution emerged. It started with a group of sex workers in Kenya who had been exposed to HIV repeatedly, yet never developed an infection. Researchers explored why and discovered that the women's immune systems appeared to naturally fight off HIV with cells specifically geared against it, rather than by developing antibodies. The shocking discovery touched off a race to develop a vaccine that replicated these HIV-targeting immune cells.

The idea of an immune-cell-driven vaccine is particularly exciting because it also holds potential as a treatment option: Those who are already infected with HIV could theoretically take the vaccine and develop a natural defense against the virus' progression to AIDS and illness. Scientists scrambled to make these dreams reality.

And in late 2004, the drug company Merck partnered with the U.S. government to conduct a large-scale clinical trial of an immune-based vaccine. They enrolled thousands of HIV-negative volunteers from around the world, gave some of them the would-be vaccine and others a placebo, and monitored the future HIV infection rates in the two cohorts. This sort of clinical trial is one of the steps a drug or vaccine must go through to win Food and Drug Administration approval -- and it's a stage no previous HIV vaccine effort had reached. Hopes soared.

Then, last September, they crashed again. An independent review board was conducting a routine safety check-in on the trial's volunteers when it discovered the vaccine was having no effect whatsoever on HIV transmission rates. In fact, the infection rate among those who took the vaccine was slightly higher than that among those given a placebo. Further, the board found no evidence that the vaccine slowed the virus' progression in the bodies of those who had become infected. Merck closed the trial down.

Vaccine research advocates have worked mightily to keep everyone from turning Merck's failure into a referendum on vaccine research broadly.  "It took 47 years after the polio virus was discovered before a vaccine was developed. Chicken pox took 42 years," said International AIDS Vaccine Initiative chief Seth Berkeley at the time the Merck trial flopped. "History tells us it takes a long time to develop a vaccine, but it also tells us it's the only way to eliminate a plague like AIDS."

Fair enough. But as Fauci offered at this week's meeting, "It was very clear that this was a disappointment." And it's one that has prompted his agency to re-evaluate what kind of research it funds. Currently, a little more than a third of the U.S. AIDS vaccine budget, 38 percent, goes toward trying to develop specific vaccine candidates. In the wake of Merck's disaster, Fauci believes it's time to dial that spending back and, instead, go back to the proverbial drawing board with what we've learned so far. He wants to fund bright, young researchers starting at square one with unexpected ideas.

Which would be great if he could afford it. But after five years of operating without a budget increase, well, good luck with that. Fauci says NIH has lost 3 percent to 4 percent purchasing power each of those five years, adding up to at least a 15 percent deficit today. "And that's what's intensified the real scientific, intellectual challenge."

No surprise, then, that things are getting testy. One advocacy group, the pugnacious AIDS Healthcare Foundation, argued that it's time to ditch vaccine research altogether and put the money into treatment and prevention. AIDS Vaccine Advocacy Coalition returned fire with a sharply worded follow-up decrying the "doom and gloom statements that boarder on the ridiculous" and chastising science reporters for playing up the troubled times.

In the end, though, the whole thing may be a reminder of a larger, uncomfortable truth about AIDS: It's with us for the long haul. Everything about our response to the epidemic -- from "emergency" treatment-subsidy programs that never have enough money to biomedical research that chases big wins -- is predicated on the notion that this is a temporary crisis. That all we have to do is plug a few holes in the public health dam until, one day soon, we find the magic solution that will make AIDS go away. The reality is that we're not a hell of a lot closer to solving HIV's riddles than we were when we discovered it in 1983. And at some point, we're going to have to build a comprehensive public health response rooted in the understanding that this is a generations-long concern.

Correction: The following quote was incorrectly attributed to the AIDS Vaccine Advocacy Coalition: ""It took 47 years after the polio virus was discovered before a vaccine was developed. Chicken pox took 42 years. History tells us it takes a long time to develop a vaccine, but it also tells us it's the only way to eliminate a plague like AIDS."

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