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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。VIRAHEP-C是一项由NIDDK-NIH赞助的多中心合作临床试验，旨在验证非洲裔美国人对抗病毒治疗的反应不如白人患者的假设。共有400名患者，平均分为非裔美国人和白种人，将在美国各地的8个临床中心登记。所有参与者均为HCV基因型1。参与者将接受48周聚乙二醇干扰素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，参与者将被随访48周。将比较两个队列之间的持续病毒学反应率（治疗后24周血清中检测不到HCV RNA）和持久持续病毒学反应率（治疗后48周血清中检测不到HCV 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用于评估非裔美国人和慢性丙型肝炎白种人对抗病毒治疗耐药的相关因素。从参与者获得的样本将进行辅助病毒学、免疫学、遗传学和干扰素信号研究，以研究抗病毒耐药的潜在机制。因此，病毒动力学（治疗期间HCV RNA从血清中清除的速率）、免疫反应、测量以及宿主和病毒遗传学将被评估与治疗反应的关系

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