1. Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults
- Author
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Philip Kotze, Fatima Laher, Mary Allen, Peter B. Gilbert, Jia J. Kee, Dishiki Jenny Kalonji, Carter Bentley, Susan W. Barnett, Tricia Philip, Craig Innes, Adrian Puren, Holly Janes, Millicent Atujuna, Nivashnee Naicker, M. Juliana McElrath, Philisiwe B. Makhoba, Gladys Kobane, Girisha Kistnasami, Katlego S. Mapetla, Zakir Gaffoor, Cleon N. Ncayiya, Sanjay Phogat, Vimla Naicker, Simbarashe Takuva, James G. Kublin, Linda-Gail Bekker, Nima S. Hejazi, David Benkeser, Niranjan Kanesa-thasan, Modulakgotla Sebe, Olivier Van Der Meeren, Yunda Huang, Bontle Modibedi, Pamela Mda, Mookho Malahleha, Mpho Sikhosana, Matsontso Mathebula, Pearl Selepe, Amy Ward, Lawrence Corey, Megan Jones, John Hural, Tania Adonis, Sheetal Kassim, Carlos Diaz Granados, Nicole Grunenberg, Shelly Ramirez, Doug Grove, Maphoshane Nchabeleng, Brittany Prigmore, Graeme Meintjes, Erica Lazarus, William Brumskine, Lubbe Wiesner, Nigel Garrett, Marguerite Koutsoukos, Thozama Dubula, Zoe Moodie, Glenda Gray, Nishanta Singh, and Michele P. Andrasik
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Adult ,Male ,Squalene ,medicine.medical_specialty ,Adolescent ,Population ,Genetic Vectors ,Immunization, Secondary ,Polysorbates ,HIV Infections ,030204 cardiovascular system & hematology ,Canarypox virus ,law.invention ,03 medical and health sciences ,South Africa ,Young Adult ,0302 clinical medicine ,Immunogenicity, Vaccine ,Randomized controlled trial ,Adjuvants, Immunologic ,Double-Blind Method ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Treatment Failure ,HIV vaccine ,education ,AIDS Vaccines ,education.field_of_study ,business.industry ,General Medicine ,Interim analysis ,Vaccine efficacy ,Vaccination ,Regimen ,AIDSVAX ,HIV-1 ,Female ,business - 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 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 ClinicalTrials.gov number, NCT02968849.).
- Published
- 2021