Transgender persons have an increased vulnerability to HIV infection yet have not been well-represented in past clinical trials for pre-exposure prophylaxis (PrEP). Because of this, there are few data available to understand whether gender-affirming hormone concentrations are influenced by PrEP agents in transgender men (TM) and transgender women (TW). The objective of this study was to compare gender-affirming hormone concentrations with versus without emtricitabine (F, FTC)–tenofovir disoproxil fumarate (TDF). TM and TW without HIV, aged 15–24 years, were enrolled for 1 month of directly observed daily F/TDF. Participants were required to be receiving a stable hormone dose (estradiol or testosterone) for at least 1 month or three consecutive doses, whichever was longer, before enrollment and willing to continue the same dose. Intensive pharmacokinetic (PK) sampling for gender-affirming hormones was collected before and 2–3 weeks after daily F/TDF. Serum estradiol and total testosterone were determined by liquid chromatography–tandem mass spectrometry; free testosterone by equilibrium dialysis. Maximum concentrations (C_max) and area under the curve (AUC_last) were log-transformed and compared between baseline and on F/TDF using geometric mean ratios (GMRs) with 95% confidence intervals (CIs). Twenty-five TW and 24 TM were enrolled (median age: 20 and 21 years, respectively). In TW, estradiol C_max (GMR [95% CI]: 0.85 [0.65–1.11]) and AUC_last (GMR [95% CI]: 0.87 [0.73–1.03]) were comparable on F/TDF versus baseline. In TM, similar comparability was observed for PrEP versus baseline including total testosterone C_max (GMR [95% CI]: 0.91 [0.80–1.03]) and AUC_last (GMR [95% CI]: 0.91 [0.81–1.04]) and free testosterone C_max (GMR [95% CI]: 0.89 [0.74–1.07]) and AUC_last (GMR [95% CI]: 0.88 [0.74–1.03]). Estradiol and testosterone exposures in young TW and TM did not significantly differ on F/TDF versus baseline. These findings should reassure patients and providers that F/TDF can be used as PrEP without concern for altering gender-affirming hormone PK. ClinicalTrials.gov (NCT03652623).

中文翻译：

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每天接受恩曲他滨/富马酸替诺福韦地索普西治疗的青少年和青年跨性别者的性别肯定激素药代动力学

跨性别者更容易感染 HIV，但在过去的暴露前预防 (PrEP) 临床试验中并未得到充分体现。正因为如此，很少有数据可用于了解变性男性 (TM) 和变性女性 (TW) 中性别肯定激素浓度是否受 PrEP 药物的影响。本研究的目的是比较使用和不使用恩曲他滨（F，FTC）-富马酸替诺福韦二吡呋酯（TDF）的性别肯定激素浓度。未感染 HIV 的 TM 和 TW，年龄在 15-24 岁之间，参加了为期 1 个月的每日直接观察 F/TDF。要求参与者在入组前接受稳定的激素剂量（雌二醇或睾酮）至少 1 个月或连续 3 次剂量，以时间较长者为准，并愿意继续相同剂量。在每日 F/TDF 之前和之后 2-3 周收集性别肯定激素的强化药代动力学 (PK) 采样。通过液相色谱-串联质谱法测定血清雌二醇和总睾酮；通过平衡透析游离睾酮。最大浓度 (C_max ) 和曲线下面积 (AUC _last ) 进行对数转换，并使用几何平均比 (GMR) 和 95% 置信区间 (CI) 在基线和 F/TDF 之间进行比较。登记了 25 名 TW 和 24 名 TM（中位年龄：分别为 20 岁和 21 岁）。在 TW 中，雌二醇_Cmax（GMR [95% CI]：0.85 [0.65–1.11]）和 AUC _last（GMR [95% CI]：0.87 [0.73–1.03]）在 F/TDF 上与基线相当。在 TM 中，观察到 PrEP 与基线的相似可比性，包括总睾酮_Cmax（GMR [95% CI]：0.91 [0.80-1.03]）和 AUC _last（GMR [95% CI]：0.91 [0.81-1.04]）和游离睾酮_Cmax（GMR [95% CI]：0.89 [0.74–1.07]）和 AUC_最后（GMR [95% CI]：0.88 [0.74–1.03]）。年轻 TW 和 TM 的雌二醇和睾酮暴露在 F/TDF 与基线方面没有显着差异。这些发现应该让患者和提供者放心，F/TDF 可以用作 PrEP，而不用担心改变性别肯定激素 PK。ClinicalTrials.gov (NCT03652623)。