Background: 

Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis (PrEP) is increasing.

Objectives: 

We aimed to investigate the impact of DMPA on PrEP drug pharmacokinetics and pharmacodynamics in women using PrEP before and after DMPA administration.

Methods: 

In this pilot study, 12 HIV-negative women ages 18–45 underwent biological sample collection at 3 time points: before study drug, after 2 weeks of daily PrEP use alone, and after 2 weeks of daily PrEP and concomitant DMPA use. We measured drug and drug metabolites in plasma, peripheral blood mononuclear cells, cervicovaginal fluid, cervical tissue, and rectal fluid after each 2-week course of PrEP. We measured HIV replication ex vivo in genital tissue biopsies and innate anti-HIV activity in cervicovaginal fluid before PrEP and after both courses. We compared drug concentrations after PrEP alone to after PrEP and DMPA in the same participant using Wilcoxon signed-rank tests. We used mixed effects linear regression models to compare pharmacodynamic measures for each participant at predrug baseline, after PrEP alone, and after PrEP and DMPA.

Results: 

We found no significant differences in PrEP drug and drug metabolite concentrations in any compartment during concomitant DMPA use compared with use of PrEP alone, except for a reduction in emtricitabine concentration in cervical tissue. We found no difference in HIV replication in cervical tissue or anti-HIV activity in cervicovaginal fluid during concomitant DMPA and PrEP use compared with during PrEP use alone.

Conclusions: 

Concomitant use of DMPA does not clinically alter pharmacokinetics or pharmacodynamics of PrEP in women. These data support the safety of DMPA use in women using PrEP.

中文翻译：

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醋酸甲羟孕酮库房使用对女性HIV暴露前预防的药代动力学和药效学影响

背景： 

醋酸甲羟孕酮（DMPA）仓库是在替诺福韦富马酸替诺福韦和恩曲他滨用于HIV暴露前预防（PrEP）的地区越来越多的避孕药具。

目标： 

我们旨在调查DMPA在使用DMPA之前和之后对使用PrEP的女性的PrEP药物药代动力学和药效学的影响。

方法： 

在这个初步研究中，12名HIV阴性妇女年龄18-45例行生物样品采集在3个时间点：研究药物前，2周每天的后PrEP的单独使用，和2周的每日后的PrEP和伴随DMPA使用。在每两周的PrEP疗程后，我们测量血浆，外周血单核细胞，宫颈阴道液，宫颈组织和直肠液中的药物和药物代谢产物。我们测量了生殖器组织活检中离体的HIV复制以及PrEP之前和两个疗程后宫颈阴道液中的先天抗HIV活性。我们比较了PrEP单独使用后与PrEP和DMPA之后的药物浓度在同一参与者中使用Wilcoxon进行秩和检验。我们采用线性回归模型混合效应比较药效措施，在给药前基线每一个参与者，后PrEP的孤独，之后的PrEP和DMPA。

结果： 

我们发现，与单独使用PrEP相比，在同时使用DMPA期间，在任何隔室中PrEP药物和药物代谢物浓度均无显着差异，只是降低了宫颈组织中恩曲他滨的浓度。我们发现伴随期间的宫颈阴道液在宫颈组织或抗HIV活性HIV复制没有区别DMPA和PrEP的用时比使用PrEP的单独使用。

结论： 

DMPA的同时使用不会在临床上改变女性PrEP的药代动力学或药效学。这些数据支持使用PrEP的女性使用DMPA的安全性。