HIV pre-exposure prophylaxis: Mucosal tissue drug distribution of RT inhibitor Tenofovir and entry inhibitor Maraviroc in a humanized mouse model

•First study in a hu-mouse model to determine pharmacokinetics of anti-HIV drugs in mucosal tissues.•In vivo analysis of anti-HIV drugs used for HIV pre-exposure prophylaxis.•Tenofovir and maraviroc showed higher levels of accumulation in mucosal tissues versus plasma.•Hu-mice are more appropriate for ARV drug PK analysis for HIV PrEP studies than non-hu mice.•Data from hu-mice PK studies will complement those from non-human primates.

Pre-exposure prophylaxis (PrEP) strategies utilizing anti-retroviral drugs show considerable promise for HIV prevention. However there is insufficient pharmacokinetic (PK) data on drug concentrations required for protection at the relevant mucosal tissues where the infection is initiated. Here we evaluated the utility of a humanized mouse model to derive PK data on two leading drugs, the RT inhibitor Tenofovir (TFV) and CCR5 inhibitor Maraviroc (MVC). Following oral dosing, both the drugs and the intracellular active TFV-diphosphate could be detected in vaginal, rectal and intestinal tissues. The drug exposures (AUC24 h) were found to be higher in vaginal tissue compared to plasma with even higher levels detected in rectal and intestinal tissues. The overall trends of drug concentrations seen in humanized mice reflect those seen in the human thus establishing the utility of this model complementing the present non-human primate (NHP) models for future pre-clinical evaluations of promising HIV PrEP drug candidates.