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

N Engl J Med

From the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (G.E.G., Z.M., N. Grunenberg, Y.H., D.G., B.P., J.J.K., J.H., C.B., S.R., S.T., M.J., M. Sikhosana, M. Andrasik, J.G.K., M.J.M., P.B.G., H.J., L.C.), Seattle; the Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand (G.E.G., F.L., E.L., B.M., T.P., S.T.), the National Institute for Communicable Diseases, National Health Laboratory Service (A.P.), and Aurum Institute (C.I., M. Sebe, W.B., P.S., T.A., G. Kobane), Johannesburg, Desmond Tutu HIV Centre (L.-G.B., S.K., C.N.N., M. Atujuna), the Department of Medicine, Wellcome Centre for Infectious Diseases Research in Africa, and Institute of Infectious Disease and Molecular Medicine (G.M., A.M.W.), and the Division of Clinical Pharmacology, Department of Medicine (L.W.), University of Cape Town, Cape Town, Setshaba Research Centre, Soshanguve (M.M., K.S.M.), Mecru Clinical Research Unit, Sefako Mkgatho Health Sciences University, Ga-Rankuwa (M.N., M.P.M.), Nelson Mandela Academic Clinical Research Unit and Department of Internal Medicine and Pharmacology, Walter Sisulu University, Mthatha (T.D., P.M.), the School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria (S.T.), the South African Medical Research Council (G.E.G., D.K., N.S., V.N., G. Kistnasami, Z.G.) and the Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal (N.N., N. Garrett), Durban, and Qhakaza Mbokodo Research Clinic, Ladysmith (P.K., P.B.M.) - all in South Africa; the Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (M. Allen), and GlaxoSmithKline Vaccines, Rockville (N.K.-T.) - both in Maryland; the Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta (D.B.); GSK Vaccines, Cambridge, MA (S.W.B.); Sanofi Pasteur, Swiftwater, PA (S.P., C.D.G.); GlaxoSmithKline, Siena, Italy (S.P.); GlaxoSmithKline, Wavre (M.K.), and GlaxoSmithKline, Rixensart (O.V.D.M.) - both in Belgium; and the Graduate Group in Biostatistics and the Center for Computational Biology, University of California, Berkeley (N.S.H.).

Published: March 2021

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.).

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888373	PMC
http://dx.doi.org/10.1056/NEJMoa2031499	DOI Listing

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