Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

Abstract In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.

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Publication Details

Journal
Nature Communications
Published
2026-04-03
DOI
https://doi.org/10.1038/s41467-026-70888-0
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

Nyaradzo Mgodi, James P. Ludwig, Michal Juraska, Lennie Chen et al.
Nature Communications
HIV Research and Treatment
article

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

Nyaradzo Mgodi, James P. Ludwig, Michal Juraska, Lennie Chen, Maurine D. Miner, Anna Yssel, Bronwen E. Lambson, Roger E. Bumgarner, Srilatha Edupuganti, Raabya Rossenkhan, Nonkululeko Ndabambi, Paula Marantz Cohen, Talita York, Dylan H. Westfall, Paul T. Edlefsen, Craig A. Magaret, David Matten, Lynn Morris, B. Murrell, Chivonne Moodley, Carolyn E. Williamson, Nicolas Beaume, Alec P. Pankow, Shelly Karuna, Bryan T. Mayer, Morgane Rolland, Ruwayhida Thebus, Haajira Kaldine, Elena E. Giorgi, Daniel B. Reeves, Hongjun Bai, Asanda Gwashu-Nyangiwe, Cindy Molitor, Sinethemba Bhebhe, Lawrence Corey, Penny L. Moore, Wenjie Deng, Myron S. Cohen, Allan C. deCamp, Hong Zhao, Nonhlanhla N. Mkhize, Tanmoy Bhattacharya, Lily Zhang, Peter B. Gilbert, David C Montefiori, John A. Hural, M. Juliana McElrath, James I. Mullins
article en

Abstract

Abstract In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.

Nature Communications
National Health Laboratory Service (ZA), South African Medical Research Council (ZA), University of North Carolina at Chapel Hill (US), Henry M. Jackson Foundation (US), Los Alamos National Laboratory (US), Emory University (US), University of Zimbabwe (ZW), University of Cape Town (ZA), University of the Witwatersrand (ZA), University of Washington (US), Centre for the AIDS Programme of Research in South Africa (ZA), Karolinska Institutet (SE), Fred Hutch Cancer Center (US), Duke Medical Center (US), Walter Reed Army Institute of Research (US), University of KwaZulu-Natal (ZA), Icahn School of Medicine at Mount Sinai (US)
Bill and Melinda Gates Foundation, Vetenskapsrådet, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 28%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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