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

Authors

• Elizabeth Hastie, University of California San Diego, San Diego, California, USA.
• Megha Srivasta, University of California San Diego, San Diego, California, USA.
• Edward R. Cachay, Mayo Clinic, Rochester, Minnesota, USA.
• Leah Burke, University of California San Diego, San Diego, California, USA.
• Sara Gianella, University of California San Diego, San Diego, California, USA.
• Stephen Rawlings, Maine Medical Center, Portland, Maine, USA.

Document Type

Article

Publication Date

5-7-2026

Journal Title

British journal of clinical pharmacology

Abstract

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: We enrolled 23 TGW, 13 on FHT and 10 CGW. Participants received five directly observed daily PrEP doses: emtricitabine 200 mg with either tenofovir disoproxil fumarate 300 mg (FTC/TDF) or tenofovir alafenamide 25 mg (FTC/TAF). Blood and rectal tissue samples were obtained. Mononuclear and CD4 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: Total nucleotide pools (pTFV and pFTC) correlated with active metabolites (TFVdp and FTCtp) in blood and rectal CD4 cells (r > 0.75, p <  .001). No significant differences in pTFV or pFTC concentrations were observed between high and low oestradiol groups in either CGW or TGW (p > .1). No correlation was observed between serum oestradiol concentrations and nucleotide concentrations. TAF resulted in 6.8-fold higher median pTFV concentrations in blood CD4 cells (p <  .001) but eightfold lower median pTFV concentrations in rectal CD4 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.

Recommended Citation

Hastie, Elizabeth; Srivasta, Megha; Cachay, Edward R.; Burke, Leah; Gianella, Sara; and Rawlings, Stephen, "PrEP at the site of action in cisgender and transgender women: A pharmacology study of blood and rectal CD4 lymphocytes" (2026). MaineHealth Maine Medical Center. 4506.
https://knowledgeconnection.mainehealth.org/mmc/4506