Title
Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials
Date Issued
01 February 2021
Access level
open access
Resource Type
journal article
Author(s)
Huang Y.
Naidoo L.
Zhang L.
Carpp L.N.
Rudnicki E.
Randhawa A.
McDermott A.
Ledgerwood J.
Lorenzo M.M.G.
Burns D.
DeCamp A.
Juraska M.
Mascola J.
Edupuganti S.
Mgodi N.
Cohen M.
Corey L.
Andrew P.
Karuna S.
Gilbert P.B.
Mngadi K.
Lazarus E.
Publisher(s)
Elsevier B.V.
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.
Volume
64
Language
English
OCDE Knowledge area
Farmacología, Farmacia
Subjects
Scopus EID
2-s2.0-85099713682
PubMed ID
Source
EBioMedicine
ISSN of the container
2352-3964
Sponsor(s)
National Institute of Allergy and Infectious Diseases UM1AI068614
Sources of information:
Directorio de Producción Científica
Scopus