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Further Analysis of STEP AIDS Vaccine Trial Reaffirms Earlier Trend

February 05, 2008

Further analysis of STEP AIDS vaccine trial data points to pre-existing Ad5 immunity and lack of circumcision as factors in heightened vulnerability to HIV infection

February 5, 2008 – A new analysis of the data from the late-stage AIDS vaccine trial known as the STEP study reinforces an earlier analysis from the trial, which suggested that pre-existing immunity to adenovirus serotype 5 (Ad5), used as the vector in the vaccine candidate, may have increased the susceptibility of trial volunteers to HIV infection. The analysis further found that male vaccinees who were uncircumcised may also have been especially vulnerable to HIV infection.

This new analysis, presented at the annual Conference on Retroviruses and Opportunistic Infections in Boston by Michael Robertson from Merck & Co., manufacturers of the vaccine candidate, and Susan Buchbinder of the University of California, San Francisco and the principal investigator of the trial, is a more thorough statistical examination of the STEP data. Vaccinations in the STEP trial were discontinued on September 21, 2007, when the trial’s Data Safety and Monitoring Board concluded the candidate was not efficacious. An initial data analysis presented on November 7 that focused on the male volunteers in the trial suggested that those who received the vaccine, which cannot cause HIV infection, might have an increased susceptibility to acquiring HIV. As of November, 49 cases of HIV infection were seen among the male volunteers who received vaccine in the trial, versus 33 among those who received placebo. The difference in the number of cases was more pronounced among volunteers with high pre-existing immunity to Ad5 and among volunteers who were not circumcised.

The recent analysis is an attempt to identify risk factors for HIV infection that might explain the higher numbers of HIV infection among recipients of vaccine as opposed to placebo. Called a multivariate regression analysis, it aims to determine the contribution of pre-existing Ad5 immunity and circumcision status to the increased susceptibility to HIV infection after adjusting for potential confounding factors such as age, race, geographical location and sexual history.

Additional multivariate analyses are planned when data have been gathered on the volunteers’ herpes simplex virus-2 status, immunological genetics, and sexual network clustering.

The precise biological mechanism behind the apparent increased risk of HIV infection remains unknown, and laboratory studies are ongoing to investigate.

About IAVI The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Founded in 1996 and operational in 24 countries, IAVI and its network of collaborators research and develop vaccine candidates.  IAVI's financial and in-kind supporters include the Alfred P. Sloan Foundation, the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, The John D. Evans Foundation, The New York Community Trust, the James B. Pendleton Charitable Trust, The Rockefeller Foundation, The Starr Foundation, The William and Flora Hewlett Foundation; the Governments of Canada, Denmark, Ireland, The Netherlands, Norway, Spain, Sweden, the United Kingdom, and the United States, the Basque Autonomous Government as well as the European Union; multilateral organizations such as The World Bank; corporate donors including BD (Becton, Dickinson & Co.), Bristol-Myers Squibb, Continental Airlines, Google Inc., Henry Schein, Inc., Merck & Co., Inc. and Pfizer Inc; leading AIDS charities such as Broadway Cares/Equity Fights AIDS and Until There's A Cure Foundation; other private donors such as The Haas Trusts; and many generous individuals from around the world.  For more information, see www.iavi.org.