The STEP Study or Phambili Trial was a clinical trial which tested the efficacy of an HIV vaccine. Vaccination in the study ended suddenly and before it was scheduled to finish when pre-determined endpoints happened and indicated that the vaccine being tested certainly was not an effective tool for preventing infection with HIV.
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Other names
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.
The branch of the study which was conducted in Africa was called the "Phambili Trial" or "HVTN 503".
Study organizers
Merck & Co. and the HIV Vaccine Trials Network (HVTN) were the study organizers. The study was co-sponsored by Merck, NIAID, and the HVTN. There was also a "STEP Study Oversight Committee" which was a group with representatives from the above three organizations.
In South Africa the trial was overseen by the South African AIDS Vaccine Initiative.
Background
STEP was the second HIV vaccine efficacy trial ever conducted.
Design
Candidates for enrollment into the study were men and women identified as 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.
Cessation
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 this African trial had been entirely vaccinated.
Response
Alan Aderem of Seattle Biomed stated that "the experimental inoculation... actually increased the chances that some people would later acquire HIV."
In May 2012 The New York Times reported that a study confirmed that the vaccine given to volunteers in the STEP Study made them more likely, not less, to become infected with HIV.