HCV and Progression of HIV and HAART Response in Women

描述：（由申请人提供）概述：最近的证据表明， 与HCV合并感染可能对HIV疾病进展产生负面影响， 对HAART的回应近40%）的妇女参加了妇女 机构间HIV研究（WMS）与HCV共感染， 有机会研究HCV对疾病进展和对 HAART。我们提出了一个两部分的研究，将包括回顾性和 利用储存库样本和临床信息进行前瞻性评价 来自WMS的368名HIV+/HCV+和650名HIV+/HCV-妇女以及30名新发现的 HAAKT天真的女人。假设：我们假设：i）感染HIV-1的妇女， 同时感染HCV的人，其H N RNA水平会增加， 与未感染HCV的女性相比，下降并进展为艾滋病，以及ii） HAART后，HCV病毒血症和肝外复制将损害病毒 对治疗的反应和免疫恢复。目的：为了解决假设一，我们 将确定HCV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。具体而言，我们将：i）研究血浆HCV RNA的作用， 准种多样性和基因型对HIV疾病进展的影响; ii）评估 PBMCs中的肝外复制，并确定其与HIV RNA的关系 HIV疾病的水平和阶段; iii）确定HCV病毒血症和肝外 复制与免疫激活，幼稚和 记忆CD 4和CD 8细胞以及胸腺输出。为了解决假设2，我们将： i）评估血浆HCV RNA、基因型、准种多样性和肝外 HAART前PBMC中的复制影响病毒学和免疫学 ii）评估HIV和HCV RNA的早期变化，以及 在一组集中随访的妇女中，HAART后免疫恢复。这些 研究将有助于我们理解这些因素之间的相互作用。 病毒在临床环境中的作用，并有助于描述 可能受益于特定的抗病毒治疗。

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.