HCV and Progression of HIV and HAART Response in Women

描述：(申请人提供)概述：最近的证据表明 与丙型肝炎病毒混合感染可能会对艾滋病毒疾病的进展和 对HAART的响应。近40%)的女性参加了 跨部门艾滋病毒研究(WMS)与丙型肝炎病毒共同感染提供了独特的 研究丙型肝炎病毒对疾病进展和反应的影响的机会 哈尔特。我们提出了一项由两部分组成的研究，包括回顾和 利用资料库样本和临床信息进行前瞻性评估 来自WMS中的368名艾滋病毒+/丙型肝炎病毒阳性妇女和650名艾滋病毒+/丙型肝炎病毒携带者和30名新发现的 哈克特-天真的女人。假设：我们假设：i)感染HIV-1的女性 合并感染丙型肝炎病毒的人会有更高的H-N-RNA水平，以及更快的CD4 与未感染丙型肝炎病毒的女性相比，下降和进展为艾滋病，以及ii) HAART后，丙型肝炎病毒血症和肝外复制将损害病毒 对治疗和免疫恢复的反应。目标：为了解决假设I，我们 将决定丙型肝炎病毒感染和疾病进展之间的关系 基于女性的流行病学、临床、病毒学和免疫学特征 在WIHS。具体地说，我们将：i)研究血浆丙型肝炎病毒RNA的影响， 准物种多样性和基因对艾滋病毒疾病进展的影响；ii)评估 外周血单核细胞的肝外复制及其与HIV-RNA的关系 艾滋病毒疾病的级别和阶段；iii)确定丙型肝炎病毒血症和肝外 复制与免疫激活、幼稚和幼稚改变有关 记忆中的CD4和CD8细胞，以及胸腺输出。为了解决假设2，我们将： 一)评估血浆丙型肝炎病毒RNA、基因、准种多样性和肝外 HAART前PBMC复制对病毒学和免疫学的影响 HAART后的反应；以及ii)评估艾滋病毒和丙型肝炎病毒RNA的早期变化 在一组密集跟踪的妇女中，HAART后的免疫恢复。这些 研究将有助于我们理解它们之间的相互作用 病毒在临床环境中的作用，并帮助描述 可能受益于特定的抗病毒疗法。

DESCRIPTION: (provided by applicant) Overview: Recent evidence indicates that co-infection with HCV may negatively impact HIV disease progression and response to HAART. Almost 40 percent) of women enrolled in the Women's Interagency HIV Study (WMS) are co-infected with HCV affording a unique opportunity to study the effect of HCV on disease progression and response to HAART. We propose a two-part study that will consist of both retrospective and prospective evaluations utilizing repository samples and clinical information from 368 HIV+/HCV+ and 650 HIV+/HCV- women in WMS and 30 newly identified HAAKT-naive women. Hypotheses: We hypothesize that: i) HIV-1 infected women who are co-infected with HCV will have increased H N RNA levels, and more rapid CD4 decline and progression to AIDS than women who are HCV uninfected, and ii) after HAART, HCV viremia and extrahepatic replication will impair viral response to therapy and immune recovery. Aims: To address hypothesis I , we will determine the relationship between HCV infection and disease progression based on epidemiologic, clinical, virologic, and immunologic features of women in WIHS. Specifically we will: i) study the effect of plasma HCV RNA, quasispecies diversity, and genotype on HIV disease progression; ii) assess for extrahepatic replication in PBMCs and determine its relationship with HIV RNA level and stage of HIV disease; iii) establish if HCV viremia and extrahepatic replication are associated with immune activation, alterations in naive and memory CD4 and CD8 cells, and thymic output. To address hypothesis 2, we will: i) assess if plasma HCV RNA, genotype, quasispecies diversity and extrahepatic replication in PBMCs prior to HAART influence virologic and immunologic response after HAART; and ii) evaluate for early changes in HIV and HCV RNA and immune recovery following HAART in a group of intensively followed women. These studies will contribute to our understanding of the interaction of these viruses in a clinical setting and help to delineate populations of women who may benefit from specific antiviral therapies.