The HVTN’s Step study, a large phase IIb trial to test the efficacy of a Merck adenovirus 5 (Ad5)-based HIV vaccine, was halted in 2007 when mid-trial analyses showed that the vaccine had no effect in preventing HIV infection. Additionally, the vaccine increased the chances of HIV infection in uncircumcised men who had previously been exposed to Ad5. The Step study was conducted primarily in North and South America, where clade B is the prevalent type of HIV, and enrolled mainly homosexual men. The HVTN Phambili (the Zulu word for “forward”) study, led by HVTN co-principal investigator Dr. Glenda Gray, tested for efficacy of the same Merck Ad5 vaccine in South Africa, where HIV infection is much more common and the predominant virus is subtype C, and enrolled mainly heterosexual men and women. Like the Step study, the Phambili study showed no protective effect of the vaccine against HIV infection.
The Phambili study was also halted in 2007 when the intermediate results of the Step study became available; only 801 of the scheduled 3000 volunteers had been enrolled in Phambili at that time, so the power of the study to draw conclusions is limited. Unlike the Step study, the Phambili study did not show any increase in HIV acquisition in uncircumcised Ad5-exposed men who had received the vaccine. Interestingly, the researchers also found that while the vaccine did not prevent infection in any sub-population of the study volunteers, vaccinated women who became infected with HIV had lower viral loads and slower CD4+ T cell decline than women who received the placebo, suggesting that men and women may have different responses to future candidate HIV vaccines.
Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, Mlisana K, Metch B, de Bruyn G, Latka MH, Roux S, Mathebula M, Naicker N, Ducar C, Carter DK, Puren A, Eaton N, McElrath MJ, Robertson M, Corey L, Kublin JG; HVTN 503/Phambili study team. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 2011 Jul;11(7):507-15.