Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials
Nature Communications, Volume 14, No. 1, Article 8299, Year 2023
Notification
URL copied to clipboard!
Description
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. © 2023, The Author(s).
Authors & Co-Authors
Reeves, Daniel B.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Mayer, Bryan T.
United States, Seattle
Fred Hutchinson Cancer Center
DeCamp, Allan C.
United States, Seattle
Fred Hutchinson Cancer Center
Huang, Yunda
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Carpp, Lindsay Nicole
United States, Seattle
Fred Hutchinson Cancer Center
Magaret, Craig A.
United States, Seattle
Fred Hutchinson Cancer Center
Juraska, Michal
United States, Seattle
Fred Hutchinson Cancer Center
Gilbert, Peter B.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Montefiori, David Charles
United States, Durham
Duke University Medical Center
Bar, Katharine J.
United States, Philadelphia
University of Pennsylvania
Schiffer, Joshua T.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Rossenkhan, Raabya
United States, Seattle
Fred Hutchinson Cancer Center
Edlefsen, Paul T.
United States, Seattle
Fred Hutchinson Cancer Center
Morris, Lynn
South Africa, Johannesburg
National Health Laboratory Service
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Mkhize, Nonhlanhla N.
South Africa, Johannesburg
National Health Laboratory Service
South Africa, Johannesburg
University of the Witwatersrand
Williamson, Carolyn
South Africa, Johannesburg
National Health Laboratory Service
Mullins, James I.
United States, Seattle
University of Washington
Seaton, Kelly E.
United States, Durham
Duke University
Tomaras, Georgia D.
United States, Durham
Duke University
Andrew, Philip
United States, Durham
Fhi 360
Mgodi, Nyaradzo Mavis
Zimbabwe, Harare
University of Zimbabwe
Ledgerwood, Julie E.
United States, Bethesda
National Institutes of Health Nih
Cohen, Myron S.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Corey, Lawrence
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Naidoo, Logashvari
South Africa, Tygerberg
South African Medical Research Council
Orrell, Catherine J.
South Africa, Cape Town
Desmond Tutu Health Foundation
Goepfert, Paul A.
United States, Birmingham
The University of Alabama at Birmingham
Casapia, Martin
Peru, Iquitos
Universidad Nacional de la Amazonia Peruana
Sobieszczyk, Magdalena E.
United States, New York
Columbia University Irving Medical Center
Karuna, Shelly T.
United States, Seattle
Fred Hutchinson Cancer Center
Edupuganti, Srilatha
United States, Atlanta
Emory University School of Medicine
Statistics
Citations: 1
Authors: 31
Affiliations: 18
Identifiers
Doi:
10.1038/s41467-023-43384-y
ISSN:
20411723
Research Areas
Infectious Diseases