Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01

• Type of Material: Article
• Authors: Yunda Huang, Fred Hutchinson Cancer Center; Lily Zhang, Fred Hutchinson Cancer Center; Shelly Karuna, Fred Hutchinson Cancer Center; Philip Andrew, Family Health International; Michal Juraska, Fred Hutchinson Cancer Center; Joshua A. Weiner, Dartmouth College; Heather Angier, Fred Hutchinson Cancer Center; Evgenii Morgan, Fred Hutchinson Cancer Center; Yasmin Azzam, Fred Hutchinson Cancer Center; Edith Swann, National Institutes of Health; Sri Edupuganti, Emory University; Nyaradzo M. Mgodi, University of Zimbabwe; Margaret E. Ackerman, Dartmouth College; Deborah Donnell, Fred Hutchinson Cancer Center; Lucio Gama, National Institutes of Health; Peter L. Anderson, University of Colorado; John Hural, Fred Hutchinson Cancer Center; Myron S. Cohen, University of North Carolina; Lawrence Corey, Fred Hutchinson Cancer Center; Richard A. Koup, National Institutes of Health; M. Juliana McElrath, Fred Hutchinson Cancer Center; Peter B. Gilbert, Fred Hutchinson Cancer Center; Maria P. Lemos, Fred Hutchinson Cancer Center
• Language: English
• Date: 2023-11-28
• Publisher: Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41467-023-43399-5
• Title of Journal or Parent Work: Nature Communications
• Volume: 14
• Start Page: 7813
• Grant/Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) U.S. Public Health Service Grants UM1 AI068614 [LOC: HIV Vaccine Trials Network] to L.C., UM1 AI068619 [LOC: HIV Prevention Trials Network] to M.S.C, UM1 AI068635 [HVTN SDMC] to P.B.G and Y.H., UM1 AI068617 [HPTN SDMC] to D.D., and UM1 AI068618 [HVTN Laboratory Center] to M.J.M.
• Keywords: Medical research; Antibodies; HIV infection
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

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.