Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
J Antimicrob Chemother. 2020 May 1;75(5):1242-1249. doi: 10.1093/jac/dkaa016.
Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones.
We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969.
Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively.
We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.
与其他成年人相比，跨性别女性感染艾滋病毒的风险增加。据报道，暴露前预防（PrEP）和性别肯定治疗之间的药物相互作用是跨性别女性接受 PrEP 率低的一个原因。我们评估了接受女性化激素治疗的跨性别女性的替诺福韦和恩曲他滨的血浆药代动力学及其活性细胞内前体，替诺福韦二磷酸盐和恩曲他滨三磷酸盐。
我们招募了未接受 PrEP 的 HIV 阴性跨性别女性（≥19 岁）。参与者每天口服替诺福韦二吡呋酯/恩曲他滨 300/200mg，持续 14 天。在替诺福韦二吡呋酯/恩曲他滨剂量后第 14 天的 0 小时（预剂量）、0.5、1、2、3、4、6、8 和 12 小时采集血浆。使用梯形法则计算血浆 AUC0-24，并与历史上 HIV 阴性顺性别成年人的几何均数比值（GMR，90%CI）进行比较。其次，以几何平均值（90%CI）描述在 0 小时和 12 小时从 PBMC 收集的替诺福韦二磷酸盐和恩曲他滨三磷酸盐。临床试验注册：NCT03270969。
在 15 名跨性别女性（平均年龄 32 岁）中，与对照组相比，替诺福韦和恩曲他滨的血浆 AUC0-24 几何平均值较低：替诺福韦，2.10 与 2.76mg·h/L，GMR 0.76（0.65-0.90），P=0.01；恩曲他滨，9.15 与 10.64mg·h/L，GMR 0.86（0.75-0.98），P=0.07。替诺福韦二磷酸盐和恩曲他滨三磷酸盐浓度高于文献中的先前报道：分别为 167.1（146.6-190.5）fmol/106 细胞和 15.4（13.8-17.3）pmol/106 细胞。
与历史上的顺性别成年人相比，我们观察到跨性别女性的替诺福韦和恩曲他滨血浆浓度较低，但替诺福韦二磷酸盐和恩曲他滨三磷酸盐在 PBMC 中的细胞内浓度高于先前报道。了解 PrEP 药代动力学在血浆和组织隔室中的差异及其对疗效的影响，对跨性别女性仍然很重要。
