Merck’s Canceled HIV Vaccine Might Have Increased Trial Participants’ Risk of Becoming HIV-Positive, Researchers Say
New evidence suggests that Merck's experimental HIV vaccine was ineffective among some trial participants with a pre-existing immunity to a common cold virus and might have increased their susceptibility to HIV infection, researchers reported Wednesday at an HIV Vaccine Trials Network conference in Seattle, the Washington Post reports (Timberg, Washington Post, 11/8). However, the researchers also said that the findings could be a statistical coincidence and that there is insufficient data to determine the full meaning of the findings, the New York Times reports (Altman/Pollack, New York Times, 11/8).
Merck in September announced that it had ended its Phase II trial, which began in late 2004 and involved 3,000 HIV-negative volunteers, after its experimental vaccine failed to prevent HIV infection in participants or prove effective in delaying the progression of the virus to AIDS. The trial was stopped by the Data and Safety Monitoring Board, an independent overseer.
Some researchers have theorized that because HIV-positive people who have stronger CD4+ T-cell responses tend to fight the virus better, a vaccine that simulated a T-cell response might be able to control HIV/AIDS. The Merck vaccine was made from a weakened version of a common cold virus that served as a mode for providing three synthetically produced genes from HIV, known as gag, pol and nef. Researchers late last month asked more than 3,000 people who participated in the trial to return to study sites for tests and additional follow-up regarding a possible increased risk of HIV (Kaiser Daily HIV/AIDS Report, 10/29).
According to the Times, conference attendees are debating whether the trial investigators should continue to observe the participants without telling them whether they received the vaccine or a placebo (New York Times, 11/8). Researchers in South Africa who were testing the same vaccine have told the 801 participants in the separate trial if they received the vaccine. A recommendation on whether to tell the 3,000 people enrolled in the study in the U.S. and Latin America will be made in about 10 days, Keith Gottesdiener, a Merck vice president, said (Washington Post, 11/8).
A preliminary analysis of the trial data released in September that examined about half of the participants in the trial indicated that those receiving the vaccine were becoming HIV-positive at about the same rate as those receiving a placebo, the Times reports. There were 24 HIV infections among those vaccinated, compared with 21 among those who received a placebo. However, a new analysis of all the trial participants found that there were 49 HIV infections in the vaccinated group, compared with 33 in the placebo group.
In addition, researchers found that increased susceptibility to HIV infection among people who received the vaccine was primarily among a group of people who had a pre-existing immunity to the common cold virus adenovirus type 5. The virus was modified and used in the vaccine, the Times reports. Among 778 male volunteers who had a high level of pre-existing immunity to adenovirus, 21 of those receiving the vaccine became HIV-positive, compared with nine who received a placebo. The difference between the groups with low levels of adenovirus immunity was not statistically significant -- 28 HIV infections among the vaccine recipients, compared with 24 in the placebo group, the researchers reported (New York Times, 11/8).
Researchers said possible reasons for the findings included behavioral factors unrelated to the biology of the vaccine, differences in circumcision rates among the participants, variations in the strain of HIV that infected participants or that the results occurred by chance, the Wall Street Journal reports (Rubenstein/Schoofs, Wall Street Journal, 11/8).
"The data are disappointing and puzzling, but we don't have definitive answers" to explain the results, Lawrence Corey of the Fred Hutchinson Cancer Research Center and leader of the study, said (Russell, San Francisco Chronicle, 11/8). "Until we answer some of these questions, we're in a bit of a holding pattern," Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said (Washington Post, 11/8).
"In my mind this doesn't damn anything. It tells you [that] you need to be very careful with every aspect" of vaccine design and testing, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said (Johnson, AP/Seattle Post-Intelligencer, 11/7). "We must regroup and recommit ourselves to developing an HIV vaccine and other new prevention weapons while providing proven HIV prevention tools to those who need them," he added (NIAID release, 11/7).