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Published on: June 23, 2011
Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition
Lawrence Corey1, Peter B Gilbert1, Michal Juraska1
1From 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.
Broadly neutralizing antibody (bnAb) VRC01 did not prevent overall human immunodeficiency virus type 1 (HIV-1) acquisition compared to placebo. However, it demonstrated proof-of-concept for bnAb efficacy against sensitive HIV-1 isolates.
Area of Science:
- Clinical Virology
- Immunology
- Infectious Disease Prevention
Background:
- The efficacy of broadly neutralizing antibodies (bnAbs) in preventing human immunodeficiency virus type 1 (HIV-1) acquisition remains uncertain.
- This study investigated the preventive potential of the bnAb VRC01 against HIV-1 infection.
Purpose of the Study:
- To evaluate the efficacy of VRC01, a broadly neutralizing antibody, in preventing HIV-1 acquisition.
- To assess the safety and effectiveness of different VRC01 dosages in at-risk populations.
Main Methods:
- Two randomized, placebo-controlled trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) enrolled at-risk individuals.
- Participants received intravenous infusions of VRC01 (10 or 30 mg/kg) or placebo every 8 weeks for 10 infusions.
- HIV-1 testing was conducted every 4 weeks, and the VRC01 inhibitory concentration (IC80) of isolates was measured.
Main Results:
- Adverse events were comparable across treatment and placebo groups in both trials.
- VRC01 did not significantly reduce overall HIV-1 incidence compared to placebo in either trial.
- However, VRC01 showed a significant 75.4% prevention efficacy against VRC01-sensitive HIV-1 isolates.
Conclusions:
- VRC01 administration did not provide statistically significant protection against overall HIV-1 acquisition.
- The study provides proof-of-concept that bnAb prophylaxis can be effective, particularly against susceptible HIV-1 strains.
- Further research into bnAbs targeting specific viral strains is warranted for effective HIV-1 prevention strategies.

