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

EBioMedicine. 2021 Feb;64:103203. doi: 10.1016/j.ebiom.2020.103203. Epub 2021 Jan 23.

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.

Keywords: Antibody mediated prevention trials; Broadly neutralising antibodies; HIV-1; Population pharmacokinetics; VRC01.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacokinetics*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Neutralizing / pharmacology*
  • Broadly Neutralizing Antibodies / pharmacology
  • Broadly Neutralizing Antibodies / therapeutic use
  • Drug Monitoring
  • Female
  • HIV Antibodies / pharmacology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Humans
  • Male
  • Middle Aged
  • Neutralization Tests
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-HIV Agents
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • HIV Antibodies