Title: Pharmacokinetics Simulations for Studying Correlates of Prevention Efficacy of Passive HIV-1 Antibody Prophylaxis in the Antibody Mediated Prevention (AMP) Study,
Abstract: A key objective in two phase 2b AMP clinical trials of VRC01 is to evaluate
whether drug concentration over time, as estimated by non-linear mixed effects
pharmacokinetics (PK) models, is associated with HIV infection rate. We
conducted a simulation study of marker sampling designs, and evaluated the
effect of study adherence and sub-cohort sample size on PK model estimates in
multiple-dose studies. With m=120, even under low adherence (about half of
study visits missing per participant), reasonably unbiased and consistent
estimates of most fixed and random effect terms were obtained. Coarsened marker
sampling schedules were also studied.