Clinical Alert: Immunizations Are Discontinued in Two HIV Vaccine Trials

An independent Data and Safety Monitoring Board (DSMB) met this week to review interim data from a large, international HIV vaccine clinical trial known as the STEP study — also referred to as the HVTN 502 or Merck V520-023 study. The clinical trial, which began enrolling volunteers in December 2004, is co-sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and the pharmaceutical company Merck & Co. Inc., which also developed and supplied the candidate vaccine. Based on a review of interim data, the DSMB concluded that the vaccine cannot be shown in this trial to prevent HIV infection or affect the course of the disease in those who become infected with HIV (the vaccine itself cannot cause HIV infection because it contains only synthetically produced snippets of viral material). Therefore, Merck and NIAID instructed all study sites to cease administering the investigational vaccine but continue scheduled follow-up visits with all volunteers until the data can be more thoroughly evaluated and a course of action is developed.

The STEP study, which enrolled 3,000 participants, was conducted by the NIAID-funded HIV Vaccine Trials Network (HVTN) and Merck. Volunteers were enrolled at sites in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States. The Phase IIb "test-of-concept" study was designed to test Merck’s candidate HIV vaccine, the MRKAd5 trivalent vaccine, which aimed to stimulate production of immune system T cells that can kill HIV-infected cells. The goal of the study was to determine if the vaccine could prevent HIV infection, reduce the amount of HIV in those who do become infected, or both.

Based on its first evaluation of interim efficacy data, the DSMB found 24 cases of HIV infection among the 741 volunteers who received at least one dose of the investigational vaccine compared with 21 cases of HIV infection among the 762 volunteers who were vaccinated with placebo. In volunteers who received at least two vaccinations, the DSMB found 19 cases of HIV infection among the 672 volunteers who received the investigational vaccine and 11 instances of HIV infection among the 691 volunteers who received the placebo. The trial partners will fully evaluate the trial data, provide additional instructions to the STEP trial sites, and provide a detailed scientific analysis of the study results in the near future.

The same Merck candidate HIV vaccine is also being tested in South Africa by the HVTN and the South African AIDS Vaccine Initiative in a separate NIAID-sponsored clinical trial known as HVTN 503 or the “Phambili” study. This study was initiated in February 2007 and has enrolled 799 individuals. Immunizations and enrollment in the Phambili study have now been paused. This allows the independent DSMB that oversees the Phambili trial to review all available HVTN 503 and STEP interim findings to determine next steps. In contrast to the STEP study where the interim analysis was almost exclusively based on results in volunteers who were men who have sex with men, the Phambili study has primarily enrolled heterosexuals at high risk for HIV.

The study investigators at each site for both the STEP (HVTN 502/ Merck V520-023) and Phambili (HVTN 503) vaccine trials have been informed of the decision to cease immunizations and are contacting study volunteers to inform them of the developments.

For additional information about the HVTN 502 and HVTN 503 trials, see http://www3.niaid.nih.gov/news/QA/step_qa.htm.

Media inquiries can be directed to the NIAID News and Public Information Branch at 301-402-1663, niaidnews@niaid.nih.gov.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov

Last reviewed: 24 September 2007
Last updated: 24 September 2007
First published: 24 September 2007
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