• Lawrence Corey, Peter B Gilbert, Michal Juraska, David C Montefiori, Lynn Morris, Shelly T Karuna, Srilatha Edupuganti, Nyaradzo M Mgodi, Allan C deCamp, Erika Rudnicki, Yunda Huang, Pedro Gonzales, Robinson Cabello, Catherine Orrell, Javier R Lama, Fatima Laher, Erica M Lazarus, Jorge Sanchez, Ian Frank, Juan Hinojosa, Magdalena E Sobieszczyk, Kyle E Marshall, Pamela G Mukwekwerere, Joseph Makhema, Lindsey R Baden, James I Mullins, Carolyn Williamson, John Hural, M Juliana McElrath, Carter Bentley, Simbarashe Takuva, Margarita M Gomez Lorenzo, David N Burns, Nicole Espy, April K Randhawa, Nidhi Kochar, Estelle Piwowar-Manning, Deborah J Donnell, Nirupama Sista, Philip Andrew, James G Kublin, Glenda Gray, Julie E Ledgerwood, John R Mascola, Myron S Cohen, and HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams.
• From the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (L.C., P.B.G., M.J., S.T.K., A.C.C., E.R., Y.H., K.E.M., J. Hural, M.J.M.E., C.B., S.T., N.E., A.K.R., N.K., D.J.D., J.G.K., G.G.), and the Departments of Global Health, Microbiology, and Medicine, University of Washington (J.I.M.), Seattle; the Department of Surgery and Duke Human Vaccine Institute, Duke University Medical Center (D.C.M.), and FHI 360 (N.S., P.A.), Durham, and the Institute for Global Health and Infectious Disease, University of North Carolina, Chapel Hill (M.S.C.) - both in North Carolina; the National Institute for Communicable Diseases of the National Health Laboratory Service (L.M.) and the Antibody Immunity Research Unit, Faculty of Health Sciences (L.M.), and the Perinatal HIV Research Unit, Faculty of Health Sciences (F.L., E.M.L., S.T.), University of the Witwatersrand, Johannesburg, the Desmond Tutu HIV Centre, Department of Medicine and Institute of Infectious Disease and Molecular Medicine (C.O.), and the Division of Medical Virology (C.W.), University of Cape Town, Cape Town, the School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria (S.T.), and the South African Medical Research Council, Tygerberg (G.G.) - all in South Africa; the Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta (S.E.); the University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe (N.M.M., P.G.M.); Servicio de Enfermedades Infecciosas y Tropicales, Hospital Nacional Dos de Mayo (P.G.), Asociación Civil Via Libre (R.C.), Asociación Civil Impacta Salud y Educación (J.R.L.), and Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales, Universidad Nacional Mayor de San Marcos (J.S.), Lima, and Association Civil Selva Amazónica, Clinical Research Site, Iquitos (J. Hinojosa) - both in Peru; the Infectious Diseases Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia (I.F.); the Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York (M.E.S.); Botswana Harvard AIDS Institute, Gaborone, Botswana (J.M.); Brigham and Women's Hospital, Harvard Medical School, Boston (L.R.B.); and the Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Rockville (M.M.G.L.), the Prevention Sciences Program, Division of AIDS (D.N.B.), and the Vaccine Research Center (J.E.L., J.R.M.), National Institute of Allergy and Infectious Diseases, NIH, Bethesda, and Johns Hopkins University School of Medicine, Baltimore (E.P.-M.) - all in Maryland.
• N. Engl. J. Med. 2021 Mar 18; 384 (11): 100310141003-1014.

BackgroundWhether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.MethodsWe enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay.ResultsAdverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates.ConclusionsVRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).Copyright © 2021 Massachusetts Medical Society.

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