Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy A Randomized Trial
Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy A Randomized Trial
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DOI：
10.7326/m16-0816
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发表时间：
2016-11-01
影响因子：
39.2
通讯作者：
Platt, Heather L.
中科院分区：
文献类型：
--
作者：
Dore, Gregory J.;Altice, Frederick;Platt, Heather L.
背景资料：丙型肝炎病毒（Hepatitis C virus，HCV）感染在注射吸毒者中较为常见，目的：评价依巴斯韦-格拉佐匹韦治疗注射吸毒者HCV感染的疗效。（临床试验政府网站：NCT 02105688）背景：澳大利亚、加拿大、法国、德国、以色列、荷兰、新西兰、挪威、西班牙、中国台湾、英国和美国。患者：301例慢性HCV基因型1、4或6感染的初治患者，至少80%依从阿片类激动剂治疗（OAT）。干预：立即治疗组（ITG）接受12周的elbasvir-grazoprevir;延迟治疗组（DTG）接受12周的安慰剂，4周不治疗，然后接受12周的开放标签elbasvir-grazoprevir。主要结局为12周时的持续病毒学应答（SVR 12），在ITG和DTG中分别进行评价。结果：ITG组SVR 12为91.5%（95%CI，86.8%~ 95.0%），DTG组活动期SVR 12为89.5%（95%CI，81.5%~ 94.8%）。基线和治疗期间的药物使用不影响SVR 12或对HCV治疗的依从性。在18例治疗后病毒复发的患者中，通过24周随访，6例可能再感染。如果假设可能的再感染为应答，ITG中的SVR 12为94.0%（CI，89.8%至96.9%）。ITG中的1例患者（1/201）和1例安慰剂期DTG（1/100）因不良事件而停止治疗。局限性：这些发现可能不适用于未接受OAT的PWID，也不适用于PWID中常见的基因型3感染者。接受OAT和elbasvir-grazoprevir治疗的HCV感染患者的SVR 12发生率较高，无论是否正在使用药物。这些结果支持消除药物使用作为接受OAT的患者接受无干扰素HCV治疗的障碍。
Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688)Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.