A5178: "PEG-IFN PLUS RBV FOR HCV CO-INFECTION"

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。设计：这是一项II期、开放标签、双臂、长期维持治疗的研究。这项试验旨在研究长期服用聚乙二醇化干扰素α-2a(聚乙二醇化干扰素-2a)是否能降低在聚乙二醇化干扰素加利巴韦林治疗期间未能达到或将丙型肝炎病毒载量维持在检测极限以下的丙型肝炎病毒/艾滋病毒混合感染者的肝纤维化进展速度。接受丙型肝炎病毒治疗的新受试者和先前接受治疗的受试者都将被纳入研究。持续时间：第一步和第二步的受试者将被跟踪最多90周。第一步和第三步的受试者将被跟踪最多96周。样本量：第一步可能需要招募多达180名受试者，这取决于初治或以前接受治疗的患者与正在进行治疗的患者的比例。总共134名受试者将被随机分到第二步：组B(67人)和组(67人)。人群：第一步：两类艾滋病毒/丙型肝炎病毒混合感染的受试者将被允许进入第一步：A.接受丙型肝炎治疗的受试者或B.在任何基于干扰素的治疗至少12周后未能实现丙型肝炎持续病毒学应答的受试者。受试者必须年满18岁，有合理的可能性进行长期随访和评估。步骤2：艾滋病毒/丙型肝炎病毒混合感染者，已经接触并耐受至少12周的聚乙二醇干扰素加利巴韦林，目前：a.在步骤1或b.接受任何其他聚乙二醇干扰素加利巴韦林方案。所有受试者必须至少接受过12周的积极治疗，并证明丙型肝炎病毒核糖核酸下降不到2对数，并在血清/血浆中检测到丙型肝炎病毒核糖核酸。步骤3：丙型肝炎病毒/艾滋病病毒混合感染者，在步骤1的12周后，丙型肝炎病毒RNA至少对数下降2个对数下降或检测不到丙型肝炎病毒RNA，并耐受步骤1治疗。方案：步骤1：所有受试者将接受：ARM A，由：？聚乙二醇化干扰素180q，每周至少12周(最多18周，等待随机化到步骤2所需的结果)？利巴韦林1-1.2克/天(以体重为基础)，为期12周(最长18周，等待随机化到步骤2所需的结果)第二步：受试者将被随机分配到以下治疗组：B组接受聚乙二醇化干扰素治疗，每周一次，每次180？g，疗程72周。？臂C是观测控制臂。步骤3：注册到步骤3的受试者将接受：D组，继续进行步骤1治疗(每周一次聚乙二醇化干扰素180？g q加利巴韦林1-1.2克/天(按体重计算))，总共72周(步骤1为12-18周，步骤3为最多60周)。然后，受试者将再接受24周的跟踪。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Design: This is a phase II, open-label, two-arm, long-term maintenance therapy study. This trial is designed to study whether long-term maintenance with pegylated-interferon alfa-2a (PEG-IFN) reduces the rate of liver fibrosis progression in subjects with HCV/HIV co-infection who have failed to achieve or maintain HCV loads below the limit of detection during treatment with PEG-IFN plus ribavirin. Both HCV treatment na¿ve and previously treated subjects will be enrolled. Duration: Subjects on Steps 1 and 2 will be followed for a maximum of 90 weeks. Subjects on Steps 1 and 3 will be followed for a maximum of 96 weeks. Sample Size: Depending on the proportion of na¿ve or previously treated vs. those rolled over from ongoing therapy, Step 1 may need to enroll up to 180 subjects. A total of 134 subjects will be randomized to Step 2: Arm B (67) and Arm (67). Population: Step 1: Two classes of HIV/HCV coinfected subjects will be admitted to Step 1: A. Subjects who are HCV treatment na¿ve or B. Subjects who failed to achieve HCV sustained virologic response to at least 12 weeks of any interferon-based therapy. Subjects must be ? 18 years of age, with reasonable likelihood for long-term follow-up and evaluation. Step 2: HIV/HCV coinfected subjects who have had exposure to and tolerated at least 12 weeks of PEG-IFN plus ribavirin and are currently: A. In Step 1 or B. On any other PEG-IFN plus ribavirin regimen. All subjects must have had at least 12 weeks of active therapy and demonstrate less than a 2-log drop in HCV RNA and have HCV RNA detectable in serum/plasma. Step 3: HCV/HIV coinfected subjects who achieved at least a 2 log-drop in HCV RNA or have undetectable HCV RNA after 12 weeks on Step 1, and who tolerated Step 1 therapy. Regimen: Step 1: all subjects will receive: Arm A consisting of: ? PEG-IFN 180 ¿g Q weekly for a minimum of 12 weeks (maximum of 18 weeks while awaiting the results required for randomization to Step 2) ? Ribavirin 1-1.2 g/day (weight based) for 12 weeks (maximum of 18 weeks while awaiting the results required for randomization to Step 2) Step 2: Subjects will be randomized to the following treatment arms: ? Arm B will be treated with PEG-IFN, given 180 ¿g once weekly for 72 weeks. ? Arm C is the observational control arm. Step 3: subjects registered to Step 3 will receive; Arm D, a continuation of Step 1 treatment (PEG-IFN 180 ¿g Q weekly plus ribavirin 1-1.2 g/day (weight based)) for a total of 72 weeks (12-18 weeks on Step 1 plus up to 60 weeks on Step 3). Subjects will then be followed for an additional 24 weeks.