Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults

BACKGROUND : A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS : In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS : In January 2020, prespecified criteria for non-efficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS : The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.Supported by grants (HHSN272201300033C and HHSN272201600012C) to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline [GSK] Biologicals) by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C; by the Bill and Melinda Gates Foundation Global Health Grant (OPP1017604) and NIAID for the manufacture and release of the gp120 clinical grade material; and by U.S. Public Health Service Grants — UM1 AI068614 to the HIV Vaccine Trials Network (HVTN), UM1 AI068635 to the HVTN Statistical and Data Management Center, and UM1 AI068618 to the HVTN Laboratory Center — from the NIAID. GSK Biologicals contributed financially to the provision of preexposure prophylaxis to trial participants. The South African Medical Research Council supported its affiliated research sites.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH