Lacombe-Duncan Ashley, Tseng Alice, Scarsi Kimberly K, Senneker Tessa, Kluger Hadas, Persad Yasmeen, Underhill Angela, Kennedy V Logan, Armstrong Ian, Fung Raymond, Bourns Amy, Nguyen Quang, Hranilovic Susan, Weisdorf Thea, Chan Louie, Kia Hannah, Halpenny Roberta, Iyer Harshita, Jeyarajah Nirubini, Kovchazov George, Tharao Wangari, Loutfy Mona
Women's College Hospital, Toronto, Ontario, Canada.
School of Social Work, University of Michigan, Ann Arbor, Michigan, USA.
Br J Clin Pharmacol. 2024 Oct;90(10):2349-2359. doi: 10.1111/bcp.16162. Epub 2024 Jul 11.
Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)].
We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (C, C and AUC) and oestradiol concentrations (C, C C and AUC) at month 2.
This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.
跨性别女性受艾滋病毒影响的比例过高。对于抗逆转录病毒治疗（ART）药物与性别确认激素疗法（GAHT），特别是女性化激素疗法（FHT）之间的负面药物相互作用（DDI）的担忧，可能导致感染艾滋病毒的跨性别女性与顺性别女性相比接受抗逆转录病毒治疗的比例较低。本研究的目的是调查FHT方案（口服雌二醇和雄激素抑制药物）的成分与抗逆转录病毒治疗方案（比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺[B/F/TAF]）的双向药代动力学效应。
我们提出了一项三臂、平行组、纵向（6个月）的药物相互作用研究方案。第1组包括15名感染艾滋病毒且正在接受FHT和抗逆转录病毒治疗的跨性别女性；第2组包括15名感染艾滋病毒且正在接受抗逆转录病毒治疗的绝经前顺性别女性；第3组包括15名未感染艾滋病毒且正在接受FHT的跨性别女性。感染艾滋病毒的女性在基线时必须正在服用或转用B/F/TAF，且病毒得到抑制≥3个月。跨性别女性必须服用稳定的每日口服雌二醇≥2毫克和抗雄激素药物（药物、和/或手术、和/或医疗）≥3个月。在第2个月采集血浆抗逆转录病毒药物浓度样本，并在第1组和第2组之间进行比较。在基线和第2个月就诊时采集血清雌二醇浓度样本，并在第1组和第3组之间进行比较。主要结局是第2个月时B/F/TAF的药代动力学参数（Cmax、Cmin和AUC）和雌二醇浓度（Cmax、Cmin、Cavg和AUC）。
本研究具有全球重要性，因为它提供了关于B/F/TAF和FHT安全联合使用的关键信息，这两种疗法对感染艾滋病毒的跨性别女性来说都是挽救生命的治疗方法。
