The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir (TFV) disoporoxil fumarate (TDF) pharmacokinetics (PK) among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV, 15–24 years of age, receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received 1 month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2–3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW [geometric mean ratio (GMR); confidence interval (95% CI): 1.06 (0.89–1.28)], whereas FTC plasma exposures were 21% higher in TM versus TW (95% CI: 1.07–1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM versus TW after controlling for creatinine clearance (CrCl), but FTC-TP in PBMC remained 46% (95% CI: 1.15–1.86) higher in TM versus TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies, suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons. Registered at ClinicalTrials.gov (NCT03652623)

中文翻译：

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恩曲他滨/富马酸替诺福韦二吡呋酯在接受性别肯定激素的跨性别青少年和未感染 HIV 的年轻人中的药代动力学


跨性别群体对 HIV 暴露前预防 (PrEP) 和性别确认激素之间的药物相互作用表示担忧。在这项研究中，我们评估了恩曲他滨（F，FTC）/替诺福韦（TFV）富马酸二吡呋酯（TDF）在接受性别肯定激素治疗（GAHT）的青少年和年轻跨性别者中的药代动力学（PK）。这是一项前瞻性观察性研究，对象为未感染 HIV 的跨性别女性 (TW) 和男性 (TM)，年龄为 15-24 岁，接受 GAHT（雌二醇加/不加螺内酯或睾酮）。参与者接受了为期 1 个月的每日直接观察 F/TDF。每周采集血浆 TFV 和 FTC 方便血样，以及外周血单核细胞 (PBMC) 和干血斑 (DBS) 中的细胞内 TFV-二磷酸 (TFV-DP) 和 FTC-三磷酸 (FTC-TP)。 F/TDF 给药 2-3 周后，进行密集 PK 采样。使用非房室方法估计 PK 参数。对 TM 和 TW 之间的数据以及顺性别成年人的历史数据进行对数转换和比较。 TM 和 TW 之间的血浆 TFV 暴露相似 [几何平均比 (GMR)；置信区间 (95% CI): 1.06 (0.89–1.28)]，而 TM 与 TW 相比，FTC 血浆暴露量高 21% (95% CI: 1.07–1.38)。在控制肌酐清除率 (CrCl) 后，TM 与 TW 之间的 PBMC 和 DBS 中的 TFV-DP 以及 DBS 中的 FTC-TP 没有差异，但 TM 中 PBMC 中的 FTC-TP 仍高 46% (95% CI: 1.15–1.86)与 TW 相比。根据历史研究，所有 PK 暴露均在预期范围内。 与 TW 相比，TM 的 FTC 暴露量较高，但两种药物的总体血浆和细胞内暴露量均在历史研究范围内，表明在青少年和年轻的跨性别者中将保留高 PrEP 功效。在临床试验中注册。政府 (NCT03652623)