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

Autor: John R. Mascola, Lily Zhang, Logashvari Naidoo, Erica Lazarus, David P. Burns, Myron S. Cohen, Michal Juraska, Yunda Huang, Lindsay N. Carpp, Kathryn Therese. Mngadi, Pedro Gonzales, April K. Randhawa, Julie E. Ledgerwood, Margarita M. Gomez Lorenzo, Allan C. deCamp, Nyaradzo Mgodi, Erika Rudnicki, Srilatha Edupuganti, Adrian B. McDermott, Shelly Karuna, Peter B. Gilbert, Philip Andrew, Lawrence Corey
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
Anti-HIV Agents
Human immunodeficiency virus (HIV)
Physiology
lcsh:Medicine
HIV Infections
HIV Antibodies
medicine.disease_cause
General Biochemistry
Genetics and Molecular Biology
Neutralization
VRC01
Young Adult
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Neutralization Tests
Broadly neutralising antibodies
medicine
Humans
Population pharmacokinetics
Antibody mediated prevention trials
Volume of distribution
lcsh:R5-920
biology
business.industry
lcsh:R
Hiv incidence
Antibodies
Monoclonal
General Medicine
Middle Aged
Antibodies
Neutralizing
Treatment Outcome
030104 developmental biology
030220 oncology & carcinogenesis
Cohort
Mixed effects
biology.protein
HIV-1
Female
Drug Monitoring
Antibody
business
lcsh:Medicine (General)
Broadly Neutralizing Antibodies
Research Paper
Zdroj: EBioMedicine, Vol 64, Iss, Pp 103203-(2021)
EBioMedicine
ISSN: 2352-3964
Popis: 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.
Databáze: OpenAIRE
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