Antiretroviral Therapy and the Hepatitis C Virus

描述（由申请人提供）：20-30%的艾滋病毒感染患者同时感染丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）。HCV/HIV合并感染患者的HCV病毒载量往往高于对照组。此外，现在有证据表明，开始有效的抗逆转录病毒治疗（ART）可能与HCV病毒载量的矛盾增加有关。HCV病毒爆发可能与血清转氨酶升高有关，血清转氨酶升高会影响临床决策，维斯停止ART维斯。以前的研究未能以系统、渐进的方式前瞻性评估这些问题。在有效的免疫重建过程中病毒载量增加的机制也没有经过详细的评估。我们提出以下具体目标来解决这些问题：1。在接受ART治疗的HCV/HIV合并感染受试者中开展并进行临床干预试验，以表征早期/晚期HCV病毒动力学以及HCV病毒载量增加的患病率、意义和发病机制。2.前瞻性评价ART治疗应答者和无应答者之间HCV准种出现的意义和作用。3.明确免疫重建过程中与HCV病毒载量增加和/或肝损伤相关的免疫学相关性。我们将测试具体的假设驱动的问题，以帮助实现我们的具体目标中描述的更广泛的目标。在努力发展丙型肝炎感染和艾滋病毒之间的关系的概念框架，我们将使用数学建模，分子流行病学和免疫学的工具来研究病毒的选择，突变和复制。

DESCRIPTION (provided by applicant): Coinfection of hepatitis C virus (HCV) with human immunodeficiency virus (HIV) occurs in 20-30% of HIV infected patients. Patients with HCV/HIV coinfection tend to have higher HCV viral loads than controls. Furthermore, there is now evidence that initiation of effective antiretroviral therapy (ART) may be associated with paradoxical increases in HCV viral load. HCV viral flare may be associated with increases in serum tranaminases which affect clinical decision making, vis a vis discontinuation of ART. Previous studies have failed to prospectively evaluate these issues in a systematic, progressive manner. The mechanisms responsible for viral load increase during effective immune reconstitution have also not undergone detailed evaluation. We propose the following Specific Aims to address these issues: 1. To develop and perform a clinical intervention trial in HCV/HIV coinfected subjects treated with ART in order to characterize early/late HCV viral kinetics as well as the prevalence, significance, and pathogenesis of HCV viral load increase. 2. To prospectively evaluate the significance and role of HCV quasispecies emergence following ART initiation between treatment responders and nonresponders. 3. To define immunologic correlates during immune reconstitution that are associated with development of increased HCV viral load and/or liver injury. We will test specific, hypothesis-driven questions to help achieve the broader goals described within our Specific Aims. In an effort to develop a conceptual framework for the relationship between hepatitis C infection and HIV, we will use the tools of mathematical modeling, molecular epidemiology and immunology to study viral selection, mutation and replication.