HCV Replication and Immune Response in HIV Coinfection

HIV 合并感染中的 HCV 复制和免疫反应

• 批准号: 6632397
• 负责人: David Richard Gretch
• 金额: $ 41.84万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632397
• 关键词: AIDS therapy; HIV infections; antiAIDS agent; biopsy; cytotoxic T lymphocyte; helper T lymphocyte; hepatitis C; hepatitis C virus; human immunodeficiency virus; human subject; human therapy evaluation; immunocytochemistry; microorganism immunology; patient oriented research; secondary infection; virus RNA; virus load; virus replication; virus virus interaction

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.

描述：丙型肝炎病毒和艾滋病毒合并感染并不罕见。 大约10%到30%的艾滋病毒感染者也是 感染HCV。许多自然史研究发现， 合并感染有更严重，更迅速的进展，肝脏疾病 而不是HIV阴性的HCV感染者。虽然发病机制 HCV肝病还不太清楚，许多人认为， 在合并感染者中观察到的肝脏疾病是由于HIV相关的免疫缺陷所致。 缺陷 这些建议的具体目标如下： 目的1：确定血清HCV RNA水平和准种复杂性， HCV感染患者合并和不合并HCV感染的多样性。本研究 将检验合并感染者有较高的HCV病毒血症的假设 准种复杂性和多样性也比那些 HIV阴性 目的2：应用原位法检测HCV感染者肝内HCVRNA 有和没有HIV合并感染的患者。这项研究将利用一个现场 基因组和复制型HCV RNA的检测，以测试假设， HIV感染者肝内HCV复制增加， 肝病严重程度。它还将测试假设，这两个HCV 复制和肝脏疾病的增加，在那些更先进的 HIV相关的免疫抑制 目的3：确定HAART对HCV病毒血症、准种复杂性和HCV感染的影响。 和多样性，肝内HCV复制，以及对HCV的免疫应答。 接受HAART治疗的HIV感染患者将接受肝脏移植。 肝内HCV复制前和12 开始HAART治疗后3个月。其他HAART治疗前和治疗后的测量将 包括HCV病毒血症、HCV准种复杂性和多样性、 肝内CD4和CD8细胞染色，外周血淋巴细胞计数增加。 淋巴增生反应。