Merck's Vaccine Might Have Increased Trial Participants' Risk Of Becoming HIV-Positive

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New evidence suggests that Merck'sexperimental HIV vaccine was ineffective among some trial participantswith a pre-existing immunity to a common cold virus and might haveincreased their susceptibility to HIV infection, researchers reportedWednesday 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 astatistical coincidence and that there is insufficient data todetermine the full meaning of the findings, the New York Times reports (Altman/Pollack, New York Times, 11/8).

Merckin September announced that it had ended its Phase II trial, whichbegan in late 2004 and involved 3,000 HIV-negative volunteers, afterits experimental vaccine failed to prevent HIV infection inparticipants or prove effective in delaying the progression of thevirus to AIDS. The trial was stopped by the Data and Safety MonitoringBoard, an independent overseer.

Some researchers havetheorized that because HIV-positive people who have stronger CD4+T-cell responses tend to fight the virus better, a vaccine thatsimulated a T-cell response might be able to control HIV/AIDS. TheMerck vaccine was made from a weakened version of a common cold virusthat served as a mode for providing three synthetically produced genesfrom HIV, known as gag, pol and nef. Researchers late last month askedmore than 3,000 people who participated in the trial to return to studysites for tests and additional follow-up regarding a possible increasedrisk of HIV (Kaiser Daily HIV/AIDS Report, 10/29).

According to the Times, conferenceattendees are debating whether the trial investigators should continueto observe the participants without telling them whether they receivedthe vaccine or a placebo (New York Times, 11/8).Researchers in South Africa who were testing the same vaccine have toldthe 801 participants in the separate trial if they received thevaccine. A recommendation on whether to tell the 3,000 people enrolledin the study in the U.S. and Latin America will be made in about 10days, Keith Gottesdiener, a Merck vice president, said (Washington Post, 11/8).

New Data

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A preliminary analysis of the trial data released in September thatexamined about half of the participants in the trial indicated thatthose receiving the vaccine were becoming HIV-positive at about thesame rate as those receiving a placebo, the Timesreports. There were 24 HIV infections among those vaccinated, comparedwith 21 among those who received a placebo. However, a new analysis ofall the trial participants found that there were 49 HIV infections inthe vaccinated group, compared with 33 in the placebo group.

Inaddition, researchers found that increased susceptibility to HIVinfection among people who received the vaccine was primarily among agroup of people who had a pre-existing immunity to the common coldvirus adenovirus type 5. The virus was modified and used in thevaccine, the Times reports. Among 778 male volunteers whohad a high level of pre-existing immunity to adenovirus, 21 of thosereceiving the vaccine became HIV-positive, compared with nine whoreceived a placebo. The difference between the groups with low levelsof adenovirus immunity was not statistically significant -- 28 HIVinfections among the vaccine recipients, compared with 24 in theplacebo group, the researchers reported (New York Times, 11/8).

Researcherssaid possible reasons for the findings included behavioral factorsunrelated to the biology of the vaccine, differences in circumcisionrates among the participants, variations in the strain of HIV thatinfected participants or that the results occurred by chance, the Wall Street Journal reports (Rubenstein/Schoofs, Wall Street Journal, 11/8).

Reaction

"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 aholding pattern," Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, said (Washington Post, 11/8).

"Inmy mind this doesn't damn anything. It tells you [that] you need to bevery careful with every aspect" of vaccine design and testing, AnthonyFauci, 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 HIVvaccine and other new prevention weapons while providing proven HIVprevention tools to those who need them," he added (NIAID release, 11/7).

Reprinted with permission from kaisernetwork.org. You can view theentire Kaiser DailyHIV/AIDS Report, search the archives, and sign up for email delivery at kaisernetwork.org/email . The Kaiser Daily HIV/AIDS Report ispublished for kaisernetwork.org, a free service of The Henry J. Kaiser FamilyFoundation.

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