A randomised study of interferon-free treatment for recently acquired hepatitis C in people who inject drugs and people with HIV coinfection (the REACT Study)

 描述(由申请人提供)：在高危人群中观察到越来越多的丙型肝炎(丙型肝炎)传播，包括注射毒品的年轻人(PWID)和艾滋病毒阳性的男男性行为(MSM)，这引起了国际上的重大关注。新型高效口服直接作用抗病毒(DAA)药物有望在个人和人群水平上治疗丙型肝炎病毒，但在边缘群体中使用它们存在重大障碍和不确定性。早期参与、检测和治疗这些人群，对限制丙型肝炎传播和持续流行具有重大潜力，然而，在无干扰素治疗的时代，坚持治疗的重要性、危险行为的改变以及随后再次感染的可能性目前知之甚少。在之前由国立卫生研究院资助的使用干扰素疗法的项目中，200多名最近感染丙型肝炎病毒的PWID/HIV阳性男男性接触者接受了治疗，证明了在这些高危人群中治疗的可行性、安全性和有效性。在这个拟议的项目中，一个独特的国际调查人员合作(称为最近获得的丙型肝炎试验(REACT)网络)被用来解决当前的关键问题。一项涉及250名新近感染丙型肝炎病毒的HIV阳性和阴性受试者的随机临床试验将被进行，以评估使用索莫布韦/GS5816的DAA联合疗法的短期(6周)疗程与标准(12周)疗程的疗效。在治疗期间，将使用新的依从性监测方法，包括电子泡罩包装和治疗药物监测，以评估对治疗的依从性及其对治疗结果的影响。受试者将在治疗后进行长达两年的跟踪，以便对最近感染丙型肝炎病毒的个人在治疗后的再感染发生率进行最广泛的评估，并通过行为问卷对现阶段参与和治疗对降低风险和改变药物和性行为的影响进行深入评估。所有分析都将在艾滋病毒阳性和阴性组中进行检查。血清和细胞将被存储起来，以便在感染的第一年内评估DAA治疗后对丙型肝炎病毒的免疫反应，并对围绕丙型肝炎病毒清除和再感染的免疫反应获得独特的见解。这些标本还将扩大最近在干扰素时代治疗的丙型肝炎患者的广泛存储库，增强一个宝贵的资源。该项目的调查结果将提供建议，指导临床医生和公共卫生政策有效管理艾滋病毒阳性和阴性的有丙型肝炎病毒风险或最近感染丙型肝炎病毒的个人和人群。

 DESCRIPTION (provided by applicant): Increasing numbers of hepatitis C (HCV) transmissions are being observed in high-risk groups including young people who inject drugs (PWID) and HIV positive men who have sex with men (MSM) causing major international concern. Novel highly effective oral directly acting antiviral (DAA) drugs promise hope for the treatment of HCV at an individual and population level, yet major barriers and uncertainty exist regarding their use in marginalised groups. Early engagement, testing and treating these populations, has significant potential to limit HCV transmission and ongoing epidemics, yet the importance of adherence, risk behaviour change and the potential for subsequent reinfection in the era of interferon free treatments are currently poorly understood. In prior NIH funded projects using interferon-based therapies, over 200 PWID/HIV positive MSM with recent HCV were engaged and treated demonstrating the feasibility, safety and efficacy of treatment in these high risk groups. In this proposed project a unique international collaboration of investigators (termed the REcently ACquired HCV Trials (REACT) network) is utilised to address critical current questions. A randomised clinical trial involving 250 HIV positive and negative subjects with recent HCV will be performed to evaluate the effectiveness of short (6 week) course therapy versus standard (12 week) course therapy with the DAA combination sofosbuvir/GS5816. During therapy novel methods of adherence monitoring including electronic blister packs and therapeutic drug monitoring will be used to assess adherence to treatment and its impact on treatment outcome. Subjects will be followed for up to 2 years post treatment allowing the most extensive evaluation of reinfection incidence post treatment in individuals with recent HCV and in-depth evaluation through behavioural questionnaires of the impact of engagement and treatment at this stage on risk reduction and drug and sexual practice change. All analyses will be examined in both HIV positive and negative groups. Serum and cells will be stored throughout to allow assessment of immunological responses to HCV following DAA treatment within the first year of infection and to gain unique insights into the immune response surrounding HCV clearance and reinfection. These specimens will also expand extensive storage banks from subjects with recent HCV treated in the interferon-era enhancing a valuable resource. Findings from this project will provide recommendations to guide clinicians and public health policy in the effective management of HIV positive and negative individuals and populations at risk for, or recently infected with HCV.