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.
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".
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.
STEP was the second HIV vaccine efficacy trial ever conducted.
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.
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.
- Edwin J. Bernard (9 February 2007). "HIV & AIDS Information :: Largest ever African HIV vaccine trial opens in South Africa". aidsmap.com. aidsmap. Retrieved 24 June 2011.
- Blake, Mary (13 November 2007). "STEP Study Volunteers to be Informed Whether They Received Vaccine or Placebo". hvtn.org. HIV Vaccine Trials Network. Retrieved 24 June 2011.
- "Press release". saavi.org.za. 23 October 2007. Retrieved 24 June 2011.
- Überla, Klaus (29 August 2008). "PLoS Pathogens: HIV Vaccine Development in the Aftermath of the STEP Study: Re-Focus on Occult HIV Infection?". plospathogens.org. Public Library of Science. Retrieved 24 June 2011.
- "Information Regarding Trials using the MRK Ad5 gag/pol/nef Vaccine". HVTN Press Release. 2007-12-21. Retrieved 2008-10-29.
- "Statement: An Update Regarding the HVTN 502 and HVTN 503 HIV Vaccine Trials". niaid.nih.gov. 23 October 2007. Retrieved 24 June 2011.
- "Phambili HIV Vaccine Trial Stopped". iavi.org. International AIDS Vaccine Initiative. 23 October 2007. Retrieved 24 June 2011.
- Song, Kyung M.; Ostrom, Carol M. (2007-11-08). "Failure of AIDS vaccine punctures soaring hopes". Seattle Times. Retrieved 2008-10-29.
- "STEP Study Volunteers to be Informed Whether They Received Vaccine or Placebo" (PDF). Merck Pharmaceuticals. 2007-11-13. Archived from the original (PDF) on August 27, 2008. Retrieved 2008-10-29.
- Alan Aderem (2011). "Fast Track to Vaccines: How Systems Biology Speeds Drug Development". Scientific American (25 April 2011): 66.
- McNeil Jr., Donald (18 May 2012). "Trial Vaccine Made Some More Vulnerable to H.I.V., Study Confirms". The New York Times. New York: NYTC. ISSN 0362-4331. Retrieved 25 May 2012.