Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults

N Engl J Med. 2021 Mar 25;384(12):1089-1100. doi: 10.1056/NEJMoa2031499.


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 nonefficacy 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 follow-up, 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. (HVTN 702 number, NCT02968849.).

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines* / immunology
  • Adjuvants, Immunologic*
  • Adolescent
  • Adult
  • Canarypox virus
  • Double-Blind Method
  • Female
  • Genetic Vectors
  • HIV Infections / prevention & control*
  • HIV-1* / genetics
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Male
  • Polysorbates*
  • South Africa
  • Squalene*
  • Treatment Failure
  • Young Adult


  • AIDS Vaccines
  • Adjuvants, Immunologic
  • MF59 oil emulsion
  • Polysorbates
  • Squalene

Associated data