The male genital tract is a potential site of viral persistence. Therefore, adequate concentrations of antiretrovirals are required to eliminate HIV replication in the genital tract. Despite higher zidovudine (ZDV) and lamivudine (3TC) concentrations in seminal plasma (SP) compared to blood plasma (BP) (SP:BP concentration ratios of 2.3 and 6.7, respectively), we have previously described lower relative intracellular concentrations of their active metabolites, zidovudine triphosphate (ZDV-TP) and lamivudine triphosphate (3TC-TP), in seminal mononuclear cells (SMCs) compared to peripheral blood mononuclear cells (PBMCs) (SMC:PBMC concentration ratios of 0.36 and 1.0, respectively). Here, we use population PK modelling-based methods to simultaneously describe parent and intracellular metabolite PK in blood, semen, and PBMCs and SMCs. From this model, time to steady-state in each matrix was estimated, and indicates that the PK of 3TC-TP and ZDV-TP in PBMC are different compared to SMC, and different between the two triphosphates.

 

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