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）：在高风险群体中观察到越来越多的丙型肝炎（HCV）传播，包括注射毒品的年轻人（PWID）和与男性发生性关系的艾滋病毒阳性男性（MSM），引起了重大的国际关注。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HCV，但在边缘化群体中使用这些药物存在重大障碍和不确定性。早期参与，检测和治疗这些人群，有显着的潜力，以限制丙型肝炎病毒的传播和正在进行的流行病，但坚持的重要性，风险行为的改变和随后的再感染的可能性在无干扰素治疗的时代，目前知之甚少。在之前NIH资助的使用基于干扰素的治疗的项目中，200多名最近感染HCV的PWID/HIV阳性MSM参与并接受治疗，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，一个独特的国际合作研究者（称为最近获得的HCV试验（REACT）网络）被用来解决当前的关键问题。将进行一项随机临床试验，涉及250例近期患有HCV的HIV阳性和阴性受试者，以评价DAA联合索非布韦/GS 5816短期（6周）疗程治疗与标准（12周）疗程治疗的有效性。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）评估治疗依从性及其对治疗结局的影响。治疗后将对受试者进行长达2年的随访，以便最广泛地评价近期HCV感染者治疗后的再感染发生率，并通过行为问卷深入评价该阶段参与和治疗对风险降低以及药物和性行为改变的影响。将在HIV阳性和阴性组中检查所有分析。血清和细胞将在整个过程中储存，以便在感染的第一年内评估DAA治疗后对HCV的免疫应答，并获得对HCV清除和再感染周围免疫应答的独特见解。这些标本也将扩大广泛的储存库，从受试者与最近的HCV治疗的干扰素时代，提高了宝贵的资源。该项目的研究结果将提供建议，指导临床医生和公共卫生政策有效管理HIV阳性和阴性个体和人群，或最近感染HCV。

 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.