Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine
Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine
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DOI：
10.1016/j.jhep.2015.03.029
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发表时间：
2015-08-01
影响因子：
25.7
通讯作者：
Cohen, Daniel E.
中科院分区：
文献类型：
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作者：
Lalezari, Jacob;Sullivan, J. Greg;Cohen, Daniel E.
背景和目标：有注射吸毒史的丙型肝炎病毒（HCV）感染患者开始和完成干扰素治疗的比例较低。本研究评价了12周的所有口服方案的奥比他韦/帕利匹韦/利托那韦和达沙布韦+利巴韦林在HCV基因型1感染的患者中稳定的阿片类药物替代therapeutic.Methods的有效性，安全性和药代动力学：这是一项II期，多中心，开放标签，单臂研究初治或聚乙二醇干扰素/利巴韦林治疗经验丰富的HCV基因型1感染的患者美沙酮或丁丙诺啡+/-纳洛酮。患者接受了12周的奥比他韦/帕利匹韦/利托那韦（25 mg/150 mg/100 mg，每日一次）和达沙布韦（250 mg，每日两次）+基于体重的利巴韦林联合制剂。主要疗效终点是持续病毒学反应12周posttreatment.Results：38例慢性美沙酮（n = 19）或丁丙诺啡（n = 19）非过敏性患者入组。共有37例患者（97.4%）在治疗后12周出现持续病毒学应答。没有患者出现病毒突破或复发。1例患者因与研究药物无关的严重不良事件（脑血管意外和肉瘤）而停药。最常见的不良事件是恶心、疲劳和头痛。8例患者治疗时血红蛋白浓度< 10 g/dl。药代动力学分析表明，美沙酮或丁丙诺啡对奥比他韦、帕利匹韦、利托那韦、达沙布韦或达沙布韦M1代谢物暴露没有临床意义的影响。美沙酮或丁丙诺啡的剂量调整是requires.Conclusions：干扰素自由方案的ombitasvir/parita previr/利托那韦和达沙布韦+利巴韦林为12周耐受性良好，并实现了持续的病毒学反应在97.4%的阿片类药物替代治疗的患者在这项研究中。这种全口服方案可能为有注射吸毒史的HCV感染患者提供一种有效的干扰素治疗替代方案。(C)2015年欧洲肝脏研究协会。由Elsevier B出版。V.保留所有权利。
Background & Aims: Hepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy.Methods: This was a phase II, multicenter, open-label, single-arm study in treatment-naive or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine +/- naloxone. Patients received 12 weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) + weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment.Results: Thirty-eight non-cirrhotic patients on chronic methadone (n = 19) or buprenorphine (n = 19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations < 10 g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required.Conclusions: The interferon-free regimen of ombitasvir/parita previr/ritonavir and dasabuvir + ribavirin for 12 weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.