Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults
Gray, Glenda E.; Bekker, Linda‑Gail; Laher, Fatima; Malahleha, Mookho; Allen, Mary; Moodie, Zoe; Grunenberg, Nicole; Huang, Yunda; Grove, Doug; Prigmore, Brittany; Kee, Jia J.; Benkeser, David; Hural, John; Innes, Craig; Lazarus, Erica; Meintjes, Graeme; Naicker, Nivashnee; Kalonji, Dishiki; Nchabeleng, Maphoshane; Sebe, Modulakgotla; Singh, Nishanta; Kotze, Philip; Kassim, Sheetal; Dubula, Thozama; Naicker, Vimla; Brumskine, William; Ncayiya, Cleon N.; Ward, Amy M.; Garrett, Nigel; Kistnasami, Girisha; Gaffoor, Zakir; Selepe, Pearl; Makhoba, Philisiwe B.; Mathebula, Matsontso P.; Mda, Pamela; Adonis, Tania; Mapetla, Katlego S.; Modibedi, Bontle; Philip, Tricia; Kobane, Gladys; Bentley, Carter; Ramirez, Shelly; Takuva, Simbarashe G.; Jones, Megan; Sikhosana, Mpho; Atujuna, Millicent; Andrasik, Michele; Hejazi, Nima S.; Puren, Adrian; Wiesner, Lubbe; Phogat, Sanjay; Granados, Carlos Diaz; Koutsoukos, Marguerite; Van Der Meeren, Olivier; Barnett, Susan W.; Kanesa‑Thasan, Niranjan; Kublin, James G.; McElrath, Juliana; Gilbert, Peter B.; Janes, Holly; Corey, Lawrence
Date:
2021-03-25
Abstract:
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.
