학술논문
Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials
Document Type
article
Author
Yunda Huang; Logashvari Naidoo; Lily Zhang; Lindsay N. Carpp; Erika Rudnicki; April Randhawa; Pedro Gonzales; Adrian McDermott; Julie Ledgerwood; Margarita M.Gomez Lorenzo; David Burns; Allan DeCamp; Michal Juraska; John Mascola; Srilatha Edupuganti; Nyaradzo Mgodi; Myron Cohen; Lawrence Corey; Philip Andrew; Shelly Karuna; Peter B. Gilbert; Kathryn Mngadi; Erica Lazarus
Source
EBioMedicine, Vol 64, Iss , Pp 103203- (2021)
Subject
Language
English
ISSN
2352-3964
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.