Specimen Processing Impacts Tissue Tenofovir PK Measurements.

Antiretroviral drug concentrations at sites of HIV exposure are important drivers that influence the development HIV pre-exposure chemoprophylaxis strategies and regimens. We assessed the effect of collection method - in the presence or absence of tissue culture media - on tenofovir (TFV) and tenofovir diphosphate (TFV-DP) concentrations in colonic biopsies. We find significant baseline inter-biopsy variation in TFV (38% CV) and TFV-DP (33% CV) concentrations. Incubation in media leads to a fluid absorption-driven 2-fold increase in tissue weight with a concomitant 75% decrease in weight-adjusted tissue TFV concentrations over 120 min. In contrast, adjusted TFV-DP concentrations decrease by only 25% over the same period, with this difference not achieving statistical significance. While colonic biopsies should be collected in the absence of media for accurate TFV concentrations, the presence of media does not significantly impact TFV-DP-dependent pharmacokinetic or pharmacodynamic assays. Appropriate assessment of tissue drug concentrations should account for biopsy collection method and drug mechanism of action.