PrEP at the site of action in cisgender and transgender women: A pharmacology study of blood and rectal CD4 ⁺ lymphocytes

BACKGROUND: Female sex hormones used in feminizing hormone therapy (FHT) may influence activation and persistence of HIV pre-exposure prophylaxis (PrEP) medications. The clinical relevance of this interaction remains unclear, particularly for transgender and cisgender women (TGW and CGW). To address this gap, we examined drug metabolites in HIV susceptible cells isolated from blood and rectal tissues of TGW and CGW. MATERIALS AND METHODS: cells were isolated and analysed for intracellular triphosphorylated nucleotides (TFVdp and FTCtp) and total nucleotide pools (pTFV and pFTC) using HPLC-MS/MS. Serum hormone concentrations were quantified via enzyme immunoassay. RESULTS AND CONCLUSION: cells compared to TDF (p = .008). These findings suggest that neither endogenous hormonal fluctuations in CGW nor exogenous FHT in TGW adversely impact intracellular PrEP pharmacology in key HIV target cells.