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High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials

Author

Listed:
  • Daniel B. Reeves

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Bryan T. Mayer

    (Fred Hutchinson Cancer Center)

  • Allan C. deCamp

    (Fred Hutchinson Cancer Center)

  • Yunda Huang

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Bo Zhang

    (Fred Hutchinson Cancer Center)

  • Lindsay N. Carpp

    (Fred Hutchinson Cancer Center)

  • Craig A. Magaret

    (Fred Hutchinson Cancer Center)

  • Michal Juraska

    (Fred Hutchinson Cancer Center)

  • Peter B. Gilbert

    (Fred Hutchinson Cancer Center
    Fred Hutchinson Cancer Center
    University of Washington)

  • David C. Montefiori

    (Duke University Medical Center)

  • Katharine J. Bar

    (University of Pennsylvania)

  • E. Fabian Cardozo-Ojeda

    (Fred Hutchinson Cancer Center)

  • Joshua T. Schiffer

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Raabya Rossenkhan

    (Fred Hutchinson Cancer Center)

  • Paul Edlefsen

    (Fred Hutchinson Cancer Center)

  • Lynn Morris

    (National Health Laboratory Service
    University of the Witwatersrand
    University of KwaZulu-Natal)

  • Nonhlanhla N. Mkhize

    (National Health Laboratory Service
    University of the Witwatersrand)

  • Carolyn Williamson

    (University of Cape Town and National Health Laboratory Service)

  • James I. Mullins

    (University of Washington
    University of Washington
    University of Washington)

  • Kelly E. Seaton

    (Duke University
    Duke University)

  • Georgia D. Tomaras

    (Duke University
    Duke University)

  • Philip Andrew

    (Family Health International)

  • Nyaradzo Mgodi

    (University of Zimbabwe College of Health Sciences)

  • Julie E. Ledgerwood

    (National Institutes of Health)

  • Myron S. Cohen

    (The University of North Carolina at Chapel Hill)

  • Lawrence Corey

    (Fred Hutchinson Cancer Center
    University of Washington)

  • Logashvari Naidoo

    (South African Medical Research Council, HPRU)

  • Catherine Orrell

    (University of Cape Town)

  • Paul A. Goepfert

    (University of Alabama at Birmingham)

  • Martin Casapia

    (Universidad Nacional de la Amazonia Peru)

  • Magdalena E. Sobieszczyk

    (New York-Presbyterian/Columbia University Irving Medical Center)

  • Shelly T. Karuna

    (Fred Hutchinson Cancer Center
    GreenLight Biosciences)

  • Srilatha Edupuganti

    (Emory University School of Medicine)

Abstract

The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300–1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.

Suggested Citation

  • Daniel B. Reeves & Bryan T. Mayer & Allan C. deCamp & Yunda Huang & Bo Zhang & Lindsay N. Carpp & Craig A. Magaret & Michal Juraska & Peter B. Gilbert & David C. Montefiori & Katharine J. Bar & E. Fab, 2023. "High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43384-y
    DOI: 10.1038/s41467-023-43384-y
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    References listed on IDEAS

    as
    1. Yoshiaki Nishimura & Rajeev Gautam & Tae-Wook Chun & Reza Sadjadpour & Kathryn E. Foulds & Masashi Shingai & Florian Klein & Anna Gazumyan & Jovana Golijanin & Mitzi Donaldson & Olivia K. Donau & Rona, 2017. "Early antibody therapy can induce long-lasting immunity to SHIV," Nature, Nature, vol. 543(7646), pages 559-563, March.
    2. Bryan T Mayer & Allan C deCamp & Yunda Huang & Joshua T Schiffer & Raphael Gottardo & Peter B Gilbert & Daniel B Reeves, 2022. "Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention," PLOS Computational Biology, Public Library of Science, vol. 18(4), pages 1-20, April.
    3. James B. Whitney & Alison L. Hill & Srisowmya Sanisetty & Pablo Penaloza-MacMaster & Jinyan Liu & Mayuri Shetty & Lily Parenteau & Crystal Cabral & Jennifer Shields & Stephen Blackmore & Jeffrey Y. Sm, 2014. "Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys," Nature, Nature, vol. 512(7512), pages 74-77, August.
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