Antiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and Humans

Abstract

Adequate antiretroviral (ARV) concentrations in lymphoid tissues are critical for optimal antiretroviral therapy (ART). While the spleen contains 25% of the body’s lymphocytes, there are minimal data on ARV penetration in this organ. This study quantified total and protein-unbound splenic ARV concentrations and determined whether drug transporters, sex, or infection status were modifiers of these concentrations in animal models and humans. Two humanized mice models (hu-HSC-Rag [ n  = 36; 18 HIV-positive (HIV + ) and 18 HIV-negative (HIV − )] and bone marrow-liver-thymus [ n  = 13; 7 HIV + and 6 HIV − ]) and one nonhuman primate (NHP) model (rhesus macaque [ n  = 18; 10 SHIV + and 8 SHIV − ]) were dosed to steady state with ARV combinations.