NIAID Director Fauci Cancels Planned HIV Vaccine Trial

Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, on Thursday canceled a planned trial of NIH's Vaccine Research Center's HIV vaccine candidate, saying that additional research is needed before the candidate is tested in humans, the New York Times reports.

According to the Times, Fauci's decision to cancel the trial came after several meetings with scientists to discuss a failed Merck vaccine candidate (Altman, New York Times, 7/18). Merck in September 2007 announced it had halted a large-scale clinical trial of its experimental HIV vaccine after the drug failed to prevent HIV infection in participants or prove effective in delaying the progression of the virus to AIDS. The vaccine candidate also might have put some trial participants at an increased risk of HIV.

The VRC candidate, called PAVE-100, is similar to the Merck vaccine in that both stimulate CD4+ T cells against HIV and both contain the cold virus adenovirus-5 (Kaiser Daily HIV/AIDS Report, 3/25). The VRC candidate also contained pieces of HIV strains from around the world to spark immunity (Chase, Wall Street Journal, 7/18).

The PAVE trial aimed to determine whether the vaccine could decrease HIV viral loads in people who received the vaccine but later contracted HIV, according to Fauci. However, Fauci said a smaller trial is needed to determine the vaccine's effect on viral loads before a larger trial is conducted. Announcing the cancellation Thursday, Fauci said researchers have realized they do not know enough about how HIV vaccines and the human immune system interact. He added that smaller studies are needed until scientists understand which immune reactions are most likely to prevent HIV (New York Times, 7/18).

VRC initially planned to enroll 8,500 people in the U.S. and Africa in the trial. In March, the agency scaled back the trial to 2,000 volunteers after the failure of the Merck HIV vaccine candidate in 2007 (Kaiser Daily HIV/AIDS Report, 3/25). Fauci on Thursday called for a "leaner, meaner" study of the vaccine candidate that aims to lower viral loads (Wall Street Journal, 7/18). According to the San Francisco Chronicle, Fauci said he wants to conduct a study that would address "one fundamental question: whether the vaccine works." The study needs to determine as soon as possible whether people who are vaccinated and subsequently contract HIV can control their viral loads better than those who contract the virus but had been given a placebo. According to the Chronicle, Fauci's "scaled-down test proposal will still do that."

At least 30 trial participants over five years will need to contract HIV after receiving the vaccine for a scaled-down trial to be effective, according to James Kublin, director of the HIV Vaccine Trials Network, which would have run the trial. It is unclear how many trial participants will need to enroll for 30 participants to contract HIV, according to the Chronicle (Russell, San Francisco Chronicle, 7/18).

Comments, Reaction
Despite the trial's cancelation, NIAID in a statement said it "believes the vaccine ... is scientifically intriguing and sufficiently different from previously tested HIV vaccines to consider testing it in a smaller, more focused clinical study." Seth Berkley, president of the International AIDS Vaccine Initiative, said researchers "can still learn something from testing the PAVE candidate in humans" but that it is "not necessary to do so in a trial involving thousands, as called for in the PAVE 100 design" (Fox, Reuters, 7/17).

Fauci emphasized that the agency is "not willing to entirely shelve the concept" of the vaccine but that a "less expensive trial, with less people, that's focused on the question of whether the vaccine can lower viral load" is necessary (Lauerman, Bloomberg/Philadelphia Inquirer, 7/18). "Show me that the vaccine works by lowering the amount of HIV in the blood. Then we will move to a larger trial that will document the link with a particular immune response," Fauci said, adding that until then, a "large trial is not justified" (New York Times, 7/18).

Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said that researchers "wanted to see the smallest, most-efficient trial to answer the question" of whether it can decrease viral loads and that "PAVE-100 wasn't seen as small or efficient enough" (Bloomberg/Philadelphia Inquirer, 7/18).

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