STUDY OF VIRAL RESISTANCE TO ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C (VIRAHEP)

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。VIRAHEP-C是一项由NIDDK-NIH赞助的多中心协作临床试验，旨在测试非洲裔美国人对抗病毒治疗的反应不如高加索患者的假设。总共有400名患者，平均分配给非裔美国人和高加索人，将在全美的八个临床中心登记。所有参与者都将是丙型肝炎病毒1型。参与者将接受为期48周的聚乙二醇化干扰素α-2a 180微克/周加利巴韦林1000-1200毫克/天的治疗。在停止治疗后，参与者将再接受48周的跟踪。将比较两组人群之间的持续病毒学应答率(治疗24周后血清中检测不到丙型肝炎病毒RNA)和持久持续病毒学应答率(治疗48周后血清中检测不到丙型肝炎病毒RNA)，以确定两个种族组之间治疗反应的差异。来自这些治疗队列的临床和病毒学数据将被用来评估与慢性丙型肝炎非裔美国人和高加索人抗病毒治疗耐药相关的因素。辅助病毒学、免疫学、遗传学和干扰素信号研究将对从参与者那里获得的样本进行，将调查抗病毒耐药的潜在机制。因此，将评估病毒动力学(治疗期间丙型肝炎病毒RNA从血清中清除的速率)、免疫学反应、测量以及宿主和病毒遗传学与治疗反应的关系。

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. VIRAHEP-C is a multicenter, collaborative clinical trial, sponsored by NIDDK-NIH, designed to test the hypothesis that African Americans respond less well to antiviral therapy than Caucasian patients. A total of 400 patients, equally divided between African American and Caucasians, will be enrolled at eight clinical centers throughout the United States. All participants will be HCV genotype 1. Participants will be treated for 48 weeks with pegylated interferon alfa-2a 180 mcg/week plus ribaviirin 1000-1200 mg/day. Participants will be followed for an additional 48 weeks after cessation of therapy. Sustained virological response rates (undetectable HCV RNA in serum 24 weeks post-treatment) and durable sustained virological response rates (undetectable HCV RNA in serum 48 weeks post-treatment) between the two cohorts will be compared to determine differences in treatment response between the two racial graoups. Clinical and virological data from these treatment cohorts will be used to evaluate factors associated with resistance to antiviral therapy in African Americans and Caucasians with chronic hepatitis C. Ancillary virology, immunology, genetics, and interferon signaling studies will be performed on samples obtained from participants will investigate potential mechanisms of antiviral resistance. Thus, viral kinetics (the rate at which HCV RNA is cleared from serum during therapy), immunological responses, measures of, and host and viral genetics will be evaluated in releationship to treatment respo