The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
Akershus University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway.
Int J Drug Policy. 2017 Sep;47:177-186. doi: 10.1016/j.drugpo.2017.05.020. Epub 2017 Jun 16.
There are few data on treatment for hepatitis C virus (HCV) infection among people with ongoing injecting drug use. This study evaluated the efficacy of response-guided therapy for chronic HCV genotypes 2/3 infection among people with ongoing injecting drug use or receiving opioid substitution therapy (OST). A secondary aim was to identify predictors of HCV treatment response.
ACTIVATE was a multicentre clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Participants were recruited from drug treatment clinics, private practices, hospital clinics and community clinics in Australia, Canada, and five countries in Europe. The primary study outcome was sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).
Among 93 people with ongoing injecting drug use or receiving OST treated for HCV genotype 2/3, 59% had recently (past month) injected drugs, 77% were receiving OST and 56% injected drugs during therapy. Overall SVR was 66% (61/93). SVR was 84% in those with undetectable HCV RNA at week 4 (12 weeks) compared to 38% in those without (24 weeks). In adjusted analysis, cirrhosis vs. no/mild fibrosis [adjusted OR (aOR) 0.33, 95% CI 0.13, 0.86] predicted reduced SVR, while response at week 4 was associated with increased SVR [aOR 8.11, 95% CI 2.73, 24.10]. Recent injecting drug use at baseline or during therapy was not associated with SVR.
This study demonstrates that people with recent injecting drug use or OST with chronic HCV can achieve responses to interferon-based therapy similar to other populations, despite injecting drugs prior to or during therapy. Cirrhosis was predictive of reduced response to HCV therapy, while response at week 4 (despite shortened therapy) was predictive of improved response.
目前针对正在使用注射毒品的慢性丙型肝炎病毒（HCV）感染者的治疗数据较少。本研究评估了针对正在使用注射毒品或接受阿片类药物替代治疗（OST）的慢性 HCV 基因型 2/3 感染者进行基于应答的治疗的疗效。次要目标是确定 HCV 治疗应答的预测因素。
ACTIVATE 是一项多中心临床试验，于 2012 年至 2014 年期间招募参与者。基因型 2/3 的参与者接受直接观察的聚乙二醇干扰素 alfa-2b 和自行给予的利巴韦林治疗 12 周（第 4 周时 HCV RNA 不可检测）或 24 周（第 4 周时 HCV RNA 可检测）。参与者来自澳大利亚、加拿大和欧洲五个国家的药物治疗诊所、私人诊所、医院诊所和社区诊所。主要研究结果是持续病毒学应答（SVR，治疗后 12 周时 HCV RNA 不可检测）。
在 93 名正在使用注射毒品或接受 OST 治疗的 HCV 基因型 2/3 感染者中，59%的人最近（过去一个月）使用过注射毒品，77%的人正在接受 OST，56%的人在治疗期间使用过注射毒品。总体 SVR 为 66%（61/93）。第 4 周（12 周）时 HCV RNA 不可检测的患者的 SVR 为 84%，而不可检测的患者为 38%（24 周）。在调整分析中，肝硬化与无/轻度纤维化相比 [调整后的比值比（aOR）0.33，95%CI 0.13，0.86] 预测 SVR 降低，而第 4 周时的应答与 SVR 增加相关 [aOR 8.11，95%CI 2.73，24.10]。基线时或治疗期间最近使用注射毒品与 SVR 无关。
本研究表明，即使在治疗前或治疗期间使用注射毒品，最近使用注射毒品或 OST 的慢性 HCV 感染者也可以对基于干扰素的治疗产生反应，类似于其他人群。肝硬化是 HCV 治疗反应降低的预测因素，而第 4 周时的应答（尽管治疗时间缩短）是治疗反应改善的预测因素。
