Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials

• Type of Material: Article
• Authors: Yunda Huang, Fred Hutchinson Cancer Research Center; Logashvari Naidoo, South African Medical Research Council; Lily Zhang, Fred Hutchinson Cancer Research Center; Lindsay N. Carpp, Fred Hutchinson Cancer Research Center; Erika Rudnicki, Fred Hutchinson Cancer Research Center; April Randhawa, Fred Hutchinson Cancer Research Center; Pedro Gonzales, Asociacion Civil Impacta Salud & Educacion; Adrian McDermott, NIAID; Jullie Ledgerwood, NIAID; Margarita M. Gomez Lorenzo, NIAID; David Burns, NIAID; Allan DeCamp, Fred Hutchinson Cancer Research Center; Michal Juraska, Fred Hutchinson Cancer Research Center; John Mascola, NIAID; Srilatha Edupuganti, Emory University; Nyaradzo Mgodi, University of Zimbabwe; Myron Cohen, University of North Carolina; Lawrence Corey, University of Washington; Philip Andrew, Family Health International 360; Shelly Karuna, Fred Hutchinson Cancer Research Center; Peter B. Gilbert, Fred Hutchinson Cancer Research Center; Kathryn Mngadi, Centre for the AIDS Programme of Research in South Africa; Erica Lazarus, University of Witwatersrand
• Language: English
• Date: 2021-01-23
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Published by Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ebiom.2020.103203
• Title of Journal or Parent Work: eBioMedicine
• Volume: 64
• Start Page: 103203
• End Page: 103203
• Grant/Funding Information: We thank the HVTN 703/HPTN 081 and HVTN 704/HPTN 085 trial teams and participants. 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] and UM1AI068619 [LOC: HIV Prevention Trials Network], UM1 AI068635 [HVTN SDMC FHCRC] and UM1AI068617 [HPTN SDMC], UM1 AI068618 [HVTN Laboratory centre FHCRC] and UM1AI068613 [HPTN Laboratory centre].; UM1 AI068635 [HVTN SDMC FHCRC] and UM1AI068617 [HPTN SDMC], UM1 AI068618 [HVTN Laboratory centre FHCRC] and UM1AI068613 [HPTN Laboratory centre].; 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] and UM1AI068619 [LOC: HIV Prevention Trials Network],
• Keywords: Life Sciences & Biomedicine; Protection; Broadly neutralising antibodies; VRC01; Antibody mediated prevention trials; HIV-1; Research & Experimental Medicine; Population pharmacokinetics; Monoclonal antibody; Safety; Science & Technology; General & Internal Medicine; Diversity; Medicine, Research & Experimental; Medicine, General & Internal
• Research Categories: Health Sciences, Public Health; Biology, Biostatistics; Health Sciences, Immunology; Health Sciences, Health Care Management

Abstract

The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise pharmacokinetics and predict HIV-1 neutralisation coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralisation coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralisation coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralisation correlate with HIV incidence.