Patel Nimish, Veve Michael, Bliss Steven, Nasiri Mona, McNutt Louise-Anne, Lazariu Victoria, Roman Martha, Miller Christopher
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
University at Albany, State University of New York, Rensselaer, NY, USA.
J Pharm Technol. 2014 Oct;30(5):159-167. doi: 10.1177/8755122514533941. Epub 2014 May 2.
Among patients with HIV and hepatitis C (HCV) coinfection, drug-drug interactions involving nonstructural protein 3/4 (NS3/4A) serine protease inhibitors for HCV infection are an important concern because these drugs affect cytochrome P450 metabolism and p-glycoprotein transporters. The primary objective was to determine the prevalence of clinically significant drug-drug interactions (CSDDIs) in HIV/HCV coinfected patients if telaprevir-based HCV therapy is added to patients' medication regimens. Secondary objectives were to identify antiretroviral therapy (ART) regimens associated with the lowest risk of CSDDI and determine the clinical risk factors. A cross-sectional study was performed among adult HIV/HCV coinfected patients. Demographics, comorbidities, social history, and medication lists were extracted from medical records. For each patient, CSDDIs were identified by entering all medications and pegylated interferon, ribavirin, and telaprevir into Lexi-Interact drug interaction software. The number and nature of CSDDIs were recorded before and after addition of telaprevir-based therapy. There were 335 patients included. Prior to the addition of telaprevir-based HCV therapy, there was a high frequency (82.1%) of any CSDDI. After the addition of telaprevir-based HCV therapy, the frequency of any CSDDI increased to 97% ( < .001). Contraindicated interactions rose from 20.0% to 38.2% of patients after addition of telaprevir-based therapy. Use of ≥10 non-HIV medications, dyslipidemia, and HIV protease inhibitors were independently associated with the occurrence of a contraindicated interaction. Clinicians considering initiating telaprevir in HIV/HCV coinfected patients should be vigilant of drug-drug interactions, particularly among patients with dyslipidemia, those using ≥10 non-HIV medications, and those using HIV protease inhibitors.
在人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）合并感染的患者中，涉及用于HCV感染的非结构蛋白3/4（NS3/4A）丝氨酸蛋白酶抑制剂的药物相互作用是一个重要问题，因为这些药物会影响细胞色素P450代谢和P-糖蛋白转运体。主要目的是确定如果在患者的药物治疗方案中添加基于特拉匹韦的HCV治疗，HIV/HCV合并感染患者中具有临床意义的药物相互作用（CSDDIs）的发生率。次要目的是确定与CSDDI风险最低相关的抗逆转录病毒治疗（ART）方案，并确定临床风险因素。对成年HIV/HCV合并感染患者进行了一项横断面研究。从病历中提取人口统计学、合并症、社会史和用药清单。对于每位患者，通过将所有药物以及聚乙二醇化干扰素、利巴韦林和特拉匹韦输入Lexi-Interact药物相互作用软件来识别CSDDIs。在添加基于特拉匹韦的治疗之前和之后记录CSDDIs的数量和性质。共纳入335例患者。在添加基于特拉匹韦的HCV治疗之前，任何CSDDI的发生率都很高（82.1%）。添加基于特拉匹韦的HCV治疗后，任何CSDDI的发生率增加到97%（P<0.001）。添加基于特拉匹韦的治疗后，禁忌相互作用的患者比例从20.0%上升到38.2%。使用≥10种非HIV药物、血脂异常和HIV蛋白酶抑制剂与禁忌相互作用的发生独立相关。考虑在HIV/HCV合并感染患者中开始使用特拉匹韦的临床医生应警惕药物相互作用，尤其是在血脂异常患者、使用≥10种非HIV药物的患者以及使用HIV蛋白酶抑制剂的患者中。
