Nature Communications (Dec 2023)
High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials
- 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. Fabian Cardozo-Ojeda,
- Joshua T. Schiffer,
- Raabya Rossenkhan,
- Paul Edlefsen,
- Lynn Morris,
- Nonhlanhla N. Mkhize,
- Carolyn Williamson,
- James I. Mullins,
- Kelly E. Seaton,
- Georgia D. Tomaras,
- Philip Andrew,
- Nyaradzo Mgodi,
- Julie E. Ledgerwood,
- Myron S. Cohen,
- Lawrence Corey,
- Logashvari Naidoo,
- Catherine Orrell,
- Paul A. Goepfert,
- Martin Casapia,
- Magdalena E. Sobieszczyk,
- Shelly T. Karuna,
- Srilatha Edupuganti
Affiliations
- Daniel B. Reeves
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Bryan T. Mayer
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Allan C. deCamp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Yunda Huang
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Bo Zhang
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lindsay N. Carpp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Craig A. Magaret
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Michal Juraska
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Peter B. Gilbert
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- David C. Montefiori
- Department of Surgery, Duke University Medical Center
- Katharine J. Bar
- Perelman School of Medicine, University of Pennsylvania
- E. Fabian Cardozo-Ojeda
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Joshua T. Schiffer
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Raabya Rossenkhan
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Paul Edlefsen
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lynn Morris
- National Institute for Communicable Diseases, National Health Laboratory Service
- Nonhlanhla N. Mkhize
- National Institute for Communicable Diseases, National Health Laboratory Service
- Carolyn Williamson
- Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service
- James I. Mullins
- Department of Global Health, University of Washington
- Kelly E. Seaton
- Center for Human Systems Immunology, Duke University
- Georgia D. Tomaras
- Center for Human Systems Immunology, Duke University
- Philip Andrew
- Family Health International
- Nyaradzo Mgodi
- Clinical Trials Research Centre, University of Zimbabwe College of Health Sciences
- Julie E. Ledgerwood
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Myron S. Cohen
- Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill
- Lawrence Corey
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Logashvari Naidoo
- South African Medical Research Council, HPRU
- Catherine Orrell
- Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town
- Paul A. Goepfert
- Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham
- Martin Casapia
- Facultad de Medicina Humana, Universidad Nacional de la Amazonia Peru
- Magdalena E. Sobieszczyk
- Division of Infectious Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, New York-Presbyterian/Columbia University Irving Medical Center
- Shelly T. Karuna
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Srilatha Edupuganti
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-023-43384-y
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 15
Abstract
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.
