Extended in vivo activity of VRC01 HIV-1 prophylaxis entails initial protective efficacy and subsequent breakthrough infections

The two parallel antibody-mediated prevention (AMP) efficacy trials evaluated whether intravenous infusion of the anti-CD4 binding site broadly neutralizing antibody VRC01 prevents HIV-1 acquisition. Here, we analyzed HIV-1 acquisition in AMP through the week 104 final study visit. Against viruses considered highly sensitive to VRC01 [80% inhibitory concentration (IC 80 ) < 1 microgram/milliliter], VRC01 prophylaxis maintained cumulative prevention efficacy of 66.3% (95% confidence interval: 32.4, 83.2%), suggesting that the antibody successfully blocked or cleared these infections. In the post–week 80 period (after the final dose at week 72), HIV diagnosis and resistance to VRC01 were more frequent and greater in the VRC01 groups versus placebo. For instance, more HIV diagnoses with viruses considered moderately sensitive or resistant to VRC01 (IC 80 ≥ 5 microgram/milliliter) were made in the VRC01 groups compared with placebo groups (11 versus 1). Plausibly, as in vivo VRC01 concentration waned, suppressed viruses—often evolving greater resistance because of selective pressure—emerged as detectable infections. Our findings suggest that, whereas single antibodies can block sensitive strains, multiple antibodies are likely required to prevent both viral escape and breakthrough infections.

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Publication Details

Journal
Science Translational Medicine
Published
2026-11-04
DOI
https://doi.org/10.1126/scitranslmed.aec3480
Primary Topic
HIV Research and Treatment
Type
article
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article

Extended in vivo activity of VRC01 HIV-1 prophylaxis entails initial protective efficacy and subsequent breakthrough infections

Javier R. Lama, Kelly E. Seaton, David C. Montefiori, Nyaradzo Mavis Mgodi et al.
Science Translational Medicine
HIV Research and Treatment
article

Extended in vivo activity of VRC01 HIV-1 prophylaxis entails initial protective efficacy and subsequent breakthrough infections

Javier R. Lama, Kelly E. Seaton, David C. Montefiori, Nyaradzo Mavis Mgodi, Michal Juraska, Yunda Huang, Glenda Gray, Srilatha Edupuganti, Myron S. Cohen, Li Li, James G. Kublin, James I. Mullins, Estelle Piwowar‐Manning, Allan C. deCamp, Nidhi K. Kochar, Catherine Orrell, Craig A. Magaret, Georgia D. Tomaras, April Kaur Randhawa, Lynn Morris, Simbarashe G. Takuva, Carolyn E. Williamson, Nirupama Sista, Dan H. Barouch, Fatima Laher, Joseph M. Makhema, Pamela Grace Mukwekwerere, Lawrence Corey, Shelly Karuna, Deborah J Donnell, Ian Frank, Morgane Rolland, Pedro Gonzáles, Erica Maxine Lazarus, M. Juliana McElrath, Peter B. Gilbert, Lindsay Nicole Carpp, Elena E. Giorgi, Magdalena E. Sobieszczyk, P. Andrew, Kevin Gillespie, Hongjun Bai, Lindsey Robert Baden, Jorge Sánchez, Brian D. Williamson, John Hural, Juan Hinojosa, Robinson L. Cabello, Lily Zhang, Beatrix Haddock
article en

Abstract

The two parallel antibody-mediated prevention (AMP) efficacy trials evaluated whether intravenous infusion of the anti-CD4 binding site broadly neutralizing antibody VRC01 prevents HIV-1 acquisition. Here, we analyzed HIV-1 acquisition in AMP through the week 104 final study visit. Against viruses considered highly sensitive to VRC01 [80% inhibitory concentration (IC 80 ) < 1 microgram/milliliter], VRC01 prophylaxis maintained cumulative prevention efficacy of 66.3% (95% confidence interval: 32.4, 83.2%), suggesting that the antibody successfully blocked or cleared these infections. In the post–week 80 period (after the final dose at week 72), HIV diagnosis and resistance to VRC01 were more frequent and greater in the VRC01 groups versus placebo. For instance, more HIV diagnoses with viruses considered moderately sensitive or resistant to VRC01 (IC 80 ≥ 5 microgram/milliliter) were made in the VRC01 groups compared with placebo groups (11 versus 1). Plausibly, as in vivo VRC01 concentration waned, suppressed viruses—often evolving greater resistance because of selective pressure—emerged as detectable infections. Our findings suggest that, whereas single antibodies can block sensitive strains, multiple antibodies are likely required to prevent both viral escape and breakthrough infections.

Science Translational MedicineVol. 18(874)
National Health Laboratory Service (ZA), South African Medical Research Council (ZA), Henry M. Jackson Foundation (US), Brigham and Women's Hospital (US), Family Health International 360 (US), Beth Israel Deaconess Medical Center (US), University of North Carolina Health Care (US), Harvard University (US), Johns Hopkins University (US), Kaiser Permanente Washington Health Research Institute (US), Emory University (US), University of Zimbabwe (ZW), University of Cape Town (ZA), Duke University (US), National University of San Marcos (PE), University of the Witwatersrand (ZA), University of Washington (US), Asociación Civil Impacta Salud y Educación (PE), Columbia University Irving Medical Center (US), Centre for the AIDS Programme of Research in South Africa (ZA), Fred Hutch Cancer Center (US), Via Libre (PE), Duke Medical Center (US), Perinatal HIV Research Unit (ZA), Institute of Infectious Disease and Molecular Medicine (ZA), University of Pretoria (ZA), University of Pennsylvania (US), Walter Reed Army Institute of Research (US), University of KwaZulu-Natal (ZA)
Openalex Percentile: Top 17%
HIV Research and Treatment
DOISourceOpenAlex
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