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HIV Vaccine Trial Shows Surprising Promise

By L. K. Regan

The world's largest HIV vaccine trial has produced results—a 31 percent reduction in HIV infections among study participants. This result was both a surprise to many HIV researchers and a sign that the lengthy search for an effective vaccine may be at least beginning to produce results. But with no one yet knowing why the vaccine works, this is only the beginning.

The vaccine trial was conducted in Thailand beginning in 2003. It enrolled 16,402 HIV-negative men and women and was the largest HIV vaccine trial yet conducted. The study was a pioneering joint effort between the U.S. Army, Thailand, the U.S. National Institute of Allergy and Infectious Diseases, Sanofi Pasteur, and Global Solutions for Infectious Diseases (GSID). The purpose of the trial was to test Sanofi's ALVAC vaccine in combination with GSID's AIDSVAX (originally developed by Genentech). Study participants were given either a combination of the two vaccines, or a placebo injection. While unimpressive in flat numerical terms—74 placebo recipients became HIV infected over the course of the study as compared with 51 vaccine subjects—this amounts to a 31 percent reduction in the risk of getting HIV for vaccine recipients.

As NIAID director and AIDS researcher Dr. Anthony Fauci told The New York Times, "I don’t want to use a word like ‘breakthrough,’ but I don’t think there’s any doubt that this is a very important result." Ordinarily researchers are looking for well over 50 percent effectiveness to consider a vaccine legitimate. But HIV vaccine trials have so far yielded little result, meaning that 31 percent effectiveness constitutes a radical leap forward. And it could not have been more unexpected, for a host of reasons. AIDSVAX was the first HIV vaccine ever tested, and it was a proven failure. Likewise, the other vaccine used in the Thailand study, ALVAC, did not seem to stimulate strong immune responses in healthy people. And thus far, combination vaccines had produced little sign of efficacy against HIV. Why the combination of two otherwise ineffective vaccines actually worked is a mystery—and means that the next step in research is not obvious.

Despite being 31 percent effective, the combined vaccine showed some signs of operating differently than a standard vaccine. For instance, researchers expected that vaccinated subjects who became infected despite vaccination would have at least some increased immunity against the virus. But in fact, no such results were found. This may indicate that the vaccines may act on the body's own white blood cells, rather than producing antibodies that counter the virus itself. Such complexities have been a feature of HIV vaccine research. While the researchers do not yet understand how this new vaccine combo might work, they see the new lines of research it offers as a way out of a trap, since traditional vaccine structures have utterly failed with HIV. For instance, in 2007, trials of a Merck vaccine were stopped after it was found that, in addition to not preventing HIV, the vaccine actually increased risk of infection for some men.

Against such a backdrop, the Thailand results are primarily a first step toward new avenues of research into the ways a vaccine might act on this complex virus. As Dr. Fauci told the Times, "For more than 20 years now, vaccine trials have essentially been failures. Now it’s like we were groping down an unlit path, and a door has been opened. We can start asking some very important questions."