Gray GE, Bekker LG, Laher F, et al. - Reports describe a modest efficacy of a canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) in decreasing infection in Thailand, and a phase 1–2a trial of an analogous regimen using HIV-1 subtype C virus indicated potent humoral and cellular responses in South Africa, so researchers here sought to assess efficacy data and additional safety data for this regimen in a larger population in South Africa. A total of 5,404 adults without HIV-1 infection were assigned to receive the vaccine (2,704 participants) or placebo (2,700 participants) in this phase 2b–3 trial.  During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group. Outcomes do not support the effectiveness of the ALVAC–gp120 regimen in preventing HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.