HCV Replication and Immune Response in HIV Coinfection

描述：与丙型肝炎病毒和艾滋病毒混合感染并不少见。 大约10%到30%的艾滋病毒感染者也是 感染了丙型肝炎病毒。许多自然历史研究发现，那些拥有 合并感染有更显著、进展更快的肝病 而不是HIV阴性的丙型肝炎病毒感染者。而其发病机制 对丙型肝炎肝病认识不深，很多人认为越晚期 合并感染的人中出现的肝病是由于艾滋病毒相关免疫 缺乏症。 这项建议的具体目标如下： 目的1：测定血清丙型肝炎病毒核糖核酸水平和准种复杂性 合并和不合并丙型肝炎病毒感染患者的多样性。本研究 将检验合并感染的人有更高的丙型肝炎病毒血症的假设 更低的准物种复杂性和多样性 艾滋病毒阴性。 目的2：原位检测丙型肝炎病毒感染者肝内丙型肝炎病毒核糖核酸 患有和不患有HIV混合感染的患者。这项研究将利用现场 检测基因组和复制的丙型肝炎病毒RNA，以检验假设 HIV感染者肝内丙型肝炎病毒复制增加，并与 肝脏疾病的严重程度。它还将检验这一假设，即两种丙型肝炎病毒 晚期患者的复制和肝脏疾病增加 艾滋病毒相关的免疫抑制。 目的3：确定HAART对丙型肝炎病毒血症、准种复杂性的影响 以及多样性、肝内丙型肝炎病毒复制和对丙型肝炎病毒的免疫反应。 接受HAART治疗的HIV感染患者将接受肝脏移植 肝内丙型肝炎病毒复制的活组织检查 在启动HAART几个月后。HAART前后的其他测量将 包括丙型肝炎病毒血症、丙型肝炎病毒准种复杂性和多样性， 肝内CD4和CD8细胞染色，外周血细胞增多 淋巴增殖性反应。

DESCRIPTION: Coinfection with hepatitis C virus and HIV is not uncommon. Approximately 10 percent to 30 percent of HIV-infected individuals are also infected with HCV. Many natural history studies have found that those with coinfection have more significant, and more rapidly progressive, liver disease than HCV-infected individuals who are HIV-negative. While the pathogenesis of HCV liver disease is not well understood, many believe that the more advanced liver disease seen in those with coinfection is due to HIV-related immune deficiency. The specific aims of this proposals are as follows: Aim 1: To determine serum HCV RNA levels and quasispecies complexity and diversity in HCV-infected patients with and without HCV coinfection. This study will test the hypothesis that those with coinfection have higher HCV viremia and lower quasispecies complexity and diversity than those who are HIV-negative. Aim 2: To determine intrahepatic HCV RNA by in situ assay in HCV-infected patients with and without HIV coinfection. This study will utilize an in situ assay for genomic and replicative HCV RNA to test the hypotheses that intrahepatic HCV replication is increased in those with HIV and correlates with liver disease severity. It will also test the hypothesis that both HCV replication and liver disease are increased in those with more advanced HIV-related immune suppression. Aim 3: To determine the effect of HAART on HCV viremia, quasispecies complexity and diversity, intrahepatic HCV replication, and the immune response to HCV. HIV infected patients who are to be treated with HAART will undergo liver biopsy for measurement of intrahepatic HCV replication both before and 12 months after initiating HAART. Other pre- and post-HAART measurements will include HCV viremia, HCV quasispecies complexity and diversity, an increase in intrahepatic staining for CD4 and CD8 cells, and an increase in peripheral lymphoproliferative responses.