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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01
Nature Communications, Volume 14, No. 1, Article 7813, Year 2023
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Description
Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.gov #NCT02716675), we conduct a post-hoc analysis and find that VRC01 clearance is 0.08 L/day faster (p = 0.005), and dose-normalized area-under-the-curve of VRC01 serum concentration over-time is 0.29 day/mL lower (p < 0.001) in PrEP users (n = 24) vs. non-PrEP users (n = 24). Consequently, PrEP users are predicted to have 14% lower VRC01 neutralization-mediated prevention efficacy against circulating HIV-1 strains. VRC01 clearance is positively associated (r = 0.33, p = 0.03) with levels of serum intestinal Fatty Acid Binding protein (I-FABP), a marker of epithelial intestinal permeability, which is elevated upon starting PrEP (p = 0.04) and after months of self-reported use (p = 0.001). These findings have implications for the evaluation of future HIV-1 mAbs and postulate a potential mechanism for mAb clearance in the context of PrEP. © 2023, The Author(s).
Authors & Co-Authors
Huang, Yunda
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Zhang, Lily
United States, Seattle
Fred Hutchinson Cancer Center
Karuna, Shelly T.
United States, Seattle
Fred Hutchinson Cancer Center
Andrew, Philip
United States, Durham
Fhi 360
Juraska, Michal
United States, Seattle
Fred Hutchinson Cancer Center
Weiner, Joshua A.
United States, Hanover
Dartmouth College
Angier, Heather E.
United States, Seattle
Fred Hutchinson Cancer Center
Swann, Edith M.
United States, Bethesda
National Institutes of Health Nih
Edupuganti, Srilatha
United States, Atlanta
Emory University School of Medicine
Mgodi, Nyaradzo Mavis
Zimbabwe, Harare
University of Zimbabwe
Ackerman, Margaret E.
United States, Hanover
Dartmouth College
Donnell, Deborah J.
United States, Seattle
Fred Hutchinson Cancer Center
Gama, Lúcio
United States, Bethesda
National Institutes of Health Nih
Anderson, Peter L.
United States, Aurora
University of Colorado Anschutz Medical Campus
Koup, Richard A.
United States, Bethesda
National Institutes of Health Nih
Hural, John A.
United States, Seattle
Fred Hutchinson Cancer Center
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
McElrath, Margaret Juliana
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Gilbert, Peter B.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Lemos, Maria P.
United States, Seattle
Fred Hutchinson Cancer Center
Statistics
Authors: 21
Affiliations: 9
Identifiers
Doi:
10.1038/s41467-023-43399-5
ISSN:
20411723
Research Areas
Health System And Policy
Infectious Diseases
Participants Gender
Male