The STEP Study and Phambili Trial were clinical trials which both tested the efficacy of a recombinant adenovirus 5 vector HIV vaccine. STEP was the second HIV vaccine efficacy trial ever conducted. Vaccination in both trials stopped before the trials were scheduled to finish, when the data safety monitoring board reviewed data from the STEP study and found that the vaccine was not preventing HIV infection.
In the Americas, STEP was also known as "HVTN 502", "Merck V520 Protocol 023", "Merck V520-023", and the "MRK Ad5 gag/pol/nef vaccine". STEP is not an acronym.
In Africa, the trial was called the "Phambili trial" or "HVTN 503".
Merck & Co. and the HIV Vaccine Trials Network (HVTN) were the study organizers. The study was co-sponsored by Merck, NIAID, and the HVTN. The "STEP Study Oversight Committee" was a group with representatives from these three organizations. In South Africa the trial was overseen by the South African AIDS Vaccine Initiative.
Candidates for enrollment into the study were men and women identified at high risk candidates for HIV infection but who were currently HIV-negative. It began in 2005 and halted the enrollment of new participants in September 2007 because of potential study-related risk to participants.
The study involved giving participants three vaccinations of adenovirus synthetically modified to contain gag, pol, and nef proteins from HIV. The replication-deficient adenovirus vector carried these HIV-1 genes into the cell. It was hoped that this delivery system would induce a cell-mediated immune response to the modified adenovirus which would both decrease infection and viral set point. Since researchers created synthetic portions of the HIV genome to be ligated into the adenovirus vector, there was no risk of contracting HIV from the vaccine.
On September 21, 2007 sponsors of the STEP study announced that further vaccination would cease and that vaccination in the Phambili Trial would be paused pending review. On October 23, 2007 the sponsors announced that the Phambili Trial would stop further immunizations.
49 of the 914 men in the vaccine group and 33 men of 922 in the placebo group had tested HIV-positive. The protocol expected that the group which had received the vaccine would have a lower or equal infection rate as compared to the control group, but this was not seen. In fact, certain groups of the vaccine recipients were seen to have higher risk of HIV infection as compared to the placebo group. Merck closed the study because the vaccine was ineffective but clear evidence that the vaccine was detrimental has not been found. By November 2007 all participants were unblinded when researchers informed them whether they had received the vaccine or placebo.
While almost everyone enrolled in the STEP study had received the full course of the vaccine when the vaccination cessation was announced, no one in Phambili, the African trial, had been entirely vaccinated.
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