University of the Incarnate Word, San Antonio, TX, United States of America.
San Antonio Military Medical Center, Fort Sam Houston, TX, United States of America.
PLoS One. 2021 May 6;16(5):e0250607. doi: 10.1371/journal.pone.0250607. eCollection 2021.
We sought to determine the prevalence of phosphodiesterase type 5 inhibitor (PDE-5) mediated drug-drug interactions (DDIs) in males with HIV infection receiving antiretroviral therapy (ART) and identify factors associated with PDE-5-mediated DDIs.
Male US Military HIV Natural History Study participants diagnosed with erectile dysfunction (ED) and having a PDE-5 inhibitor and potentially-interacting ART co-dispensed within 30 days were included. DDIs were defined according to criteria found in published guidelines and drug information resources. The primary outcome of interest was overall PDE-5 inhibitor-mediated DDI prevalence and episode duration. A secondary logistic regression analysis was performed on those with and without DDIs to identify factors associated with initial DDI episode.
A total of 235 male participants with ED met inclusion criteria. The majority were White (50.6%) or African American (40.4%). Median age at medication co-dispensing (45 years), duration of HIV infection (14 years), and duration of ED (1 year) did not differ between the two groups (p>0.05 for all). PDE-5 inhibitors included sildenafil (n = 124), vardenafil (n = 99), and tadalafil (n = 14). ART regimens included RTV-boosted protease inhibitors (PIs) atazanavir (n = 83) or darunavir (n = 34), and COBI-boosted elvitegravir (n = 43). Potential DDIs occurred in 181 (77.0%) participants, of whom 122 (67.4%) had multiple DDI episodes. The median DDI duration was 8 (IQR 1-12) months. In multivariate analyses, non-statistically significant higher odds of DDIs were observed with RTV-boosted PIs or PI-based ART (OR 2.13, 95% CI 0.85-5.37) and in those with a diagnosis of major depressive disorder (OR 1.74, 95% CI 0.83-3.64).
PDE-5-mediated DDIs were observed in the majority of males with HIV infection on RTV- or COBI-boosted ART in our cohort. This study highlights the importance of assessing for DDIs among individuals on ART, especially those on boosted regimens.
我们旨在确定接受抗逆转录病毒疗法(ART)的 HIV 感染男性中磷酸二酯酶 5 抑制剂(PDE-5)介导的药物-药物相互作用(DDI)的流行率,并确定与 PDE-5 介导的 DDI 相关的因素。
纳入了在美国军事 HIV 自然史研究中诊断为勃起功能障碍(ED)且在 30 天内同时开具 PDE-5 抑制剂和潜在相互作用的 ART 的男性参与者。DDI 根据已发表的指南和药物信息资源中的标准定义。主要观察结果是 PDE-5 抑制剂介导的 DDI 总体流行率和发作持续时间。对有和没有 DDI 的患者进行二次逻辑回归分析,以确定与初始 DDI 发作相关的因素。
共有 235 名患有 ED 的男性参与者符合纳入标准。大多数为白人(50.6%)或非裔美国人(40.4%)。药物共配药时的中位年龄(45 岁)、HIV 感染时间(14 年)和 ED 持续时间(1 年)在两组之间无差异(所有 P>0.05)。PDE-5 抑制剂包括西地那非(n = 124)、伐地那非(n = 99)和他达拉非(n = 14)。ART 方案包括利托那韦增强蛋白酶抑制剂(PI)阿扎那韦(n = 83)或达鲁那韦(n = 34)和考比司他增强艾维雷格韦(n = 43)。181 名(77.0%)参与者发生潜在的 DDI,其中 122 名(67.4%)有多个 DDI 发作。DDI 的中位持续时间为 8(IQR 1-12)个月。多变量分析显示,利托那韦增强 PI 或基于 PI 的 ART(OR 2.13,95%CI 0.85-5.37)和诊断为重度抑郁症(OR 1.74,95%CI 0.83-3.64)的患者发生 DDI 的可能性更高,但无统计学意义。
在我们的队列中,大多数接受利托那韦或考比司他增强的 ART 的 HIV 感染男性中观察到 PDE-5 介导的 DDI。这项研究强调了在接受 ART 的个体中评估 DDI 的重要性,尤其是在接受增强方案的个体中。