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The results of the world's first phase 3 HIV vaccine efficacy trial are reported in the March 1, 2005 issue of The Journal Infectious Diseases, now available online. Although the vaccine was ineffective in preventing HIV infection, the trial represents a landmark in the fight against HIV and offers the scientific community a foundation on which to build future trials.
The multi-centered trial, conducted in the United States and the Netherlands and completed in 2003, is described in two papers by the rgp120 HIV Vaccine Study Group, and Peter B. Gilbert and colleagues, which address the vaccine efficacy results and the immunologic responses of the study participants.
The vaccine, produced by VaxGen, was a recombinant construct of the HIV envelope glycoprotein, similar to the type of vaccine used to develop a vaccine for hepatitis B. The vaccine was tested in a double-blind, randomized study of healthy participants who did not use intravenous drugs. The volunteers were men who have sex with men or women at high risk for heterosexual transmission. The vaccine and placebo were given by injection seven times over 30 months and the participants were assessed for risk. At each visit the participants were tested for HIV infection, and for those who were positive, HIV-1 plasma RNA load and CD4 cell counts were monitored on a regular basis for 24 months after the initial diagnosis.
Of the 5,417 volunteers who were enrolled, 368 became infected during the study. The vaccine was found not to be effective in preventing HIV infection; infection rates among those who were given the vaccine and those who were given placebo were 6.7 percent and 7.0 percent, respectively. Of those who became infected during the study, pre-treatment viral loads were similar in the placebo and vaccine groups over their follow-up visits.
During analysis of various subgroups of the study population, a higher, though statistically insignificant, vaccine efficacy was found in the high-risk and the non-white groups. The authors suggested two plausible explanations, one for each group. Those with high-risk behavior may have been exposed frequently to HIV and a primed immune response, probably cellular or humoral, could have worked with the vaccine and caused a greater ability to resist the virus. For the non-white group, the authors suggest that biological differences in immune response or genetic markers of resistance to infection could have made the vaccine more effective.
Also examined in the trial were the immune responses to the vaccine. The vaccine was able to generate antibody responses in virtually all participants, and, in general, those with a higher response had a lower rate of infection than the placebo group. In an editorial accompanying the two papers, Barney Graham and John Mascola of the Vaccine Research Center of the National Institutes for Health commented that more research is needed to be sure whether a high vaccine antibody response is related to a lower incidence of HIV infection. Citing the possible slight vaccine efficacy for non-white and high-risk participants of the trial, they urged that future vaccines be studied in a wide range of racial, ethnic, and diverse risk-level groups. They concluded that the landmark study will inform future studies, and an HIV vaccine will be found only through robust public and private investment as well as a well-informed public and scientific community.
Source: Infectious Diseases Society of America (IDSA)