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：与丙型肝炎病毒和HIV共同感染并不少见。 大约10％至30％的艾滋病毒感染者也是 感染HCV。许多自然历史研究发现 共同感染具有更大的显着性，更快的肝病 比感染HIV阴性的HCV感染者。而 HCV肝病尚不清楚，许多人认为更先进 在共同感染的患者中看到的肝病是由于HIV相关的免疫 不足。 该建议的具体目的如下： 目标1：确定血清HCV RNA水平和准菜的复杂性和 HCV感染的患者有或没有HCV共感染的患者的多样性。这项研究 将检验以下假设，即患有共同感染的人患有较高的HCV病毒血症 和较低的准人的复杂性和多样性比那些 HIV阴性。 AIM 2：通过HCV感染的原位测定确定肝内HCV RNA 有和没有HIV共同感染的患者。这项研究将利用原位 基因组和复制性HCV RNA的测定，以检验假设 肝内HCV复制增加了HIV患者，与 肝病的严重程度。它还将检验两个HCV的假设 患有更先进的人的复制和肝病增加 与HIV相关的免疫抑制。 目标3：确定HAART对HCV病毒血症的影响，准菜的复杂性 以及多样性，肝内HCV复制以及对HCV的免疫反应。 艾滋病毒感染的患者将接受HAART治疗 在肝内HCV复制之前和12 启动Haart几个月后。其他临时测量和后测量 包括HCV病毒血症，HCV准典型的复杂性和多样性，增加 CD4和CD8细胞的肝内染色，周围增加 淋巴增生反应。