HCV and HIV Progression in Women on HAART

接受 HAART 治疗的女性 HCV 和 HIV 进展情况

基本信息

  • 批准号:
    7930347
  • 负责人:
  • 金额:
    $ 7.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-26 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Overview: Although there is consensus that HIV accelerates hepatitis C (HCV) disease in co-infected (HIV+HCV+) patients, studies differ regarding the impact of HCV infection on HIV disease progression. This proposal seeks continued support for our grant HCV and Progression of HIV and HAART Response in Women . During the past 5 years we found that HCV accelerates HIV disease progression and that this is related to immune activation and altered T cell maturation as a result of dual viral infection. Our central hypothesis is that HIV disease progression is impacted by enhanced CD8 activation and altered T cell maturation as a result of HCV viral dynamics and that HAART will not completely reverse this in the setting of ongoing HCV replication. Specific Aims: 1) Determine the relationships among extrahepatic replication of HCV in PBMC, HCV dynamics and HIV disease progression in co-infected HCV viremic women. 2) Longitudinally investigate the relationship of T cell activation/maturation and function and a) HCV quasispecies dynamics and extrahepatic reservoirs. b) Disease progression. 3) Assess the relationship of HCV reservoirs in PBMC and HCV quasispecies dynamics with HIV viral load response (VLR) and rebound post-HAART. 4) Determine the relationship of immune activation and T cell maturation/function with HIV VLR and rebound post-HAART and correlate with extrahepatic replication and quasispecies diversity. Clinical Significance: Our studies thus far find that compared with singly infected women, co-infected women had: a) an almost two-fold increased probability of developing AIDS among women who never had CD4 counts < 200 cells/mm3; b) an increased relative hazard (RH) of AIDS and death at lower HIV RNA levels; c) increased RH of AIDS associated with higher levels of activated CD8+ T cells; they also had d) a 40% prevalence of HCV replication in PBMC which was associated with alcohol use and prior AIDS; and, e) a 3 fold increase in changes in HCV quasispecies among active IDU. These findings support our hypothesis that HCV dynamics contributes to immune dysregulation and the development of AIDS and AIDS-related death. Co- infected women may need to initiate antiretroviral treatment (ART) at lower HIV RNA and higher CD4 count thresholds than is currently recommended, to prevent AIDS/death. Given the many clinical, demographic and behavioral characteristics associated with HIV disease progression, a large cohort is needed. The proposed study will allow us to better define those who may benefit from more aggressive ART.In this study we will determine the relationships among extrahepatic HCV replication in PBMC, HCV dynamics and a) HIV disease progression; b) long-term response to HAART among HIV infected and HIV and HCV co- infected women from the Women's Interagency HIV Study. Further, we will longitudinally investigate the relationship of T cell activation/maturation and function with a) HCV quasispecies dynamics and extrahepatic reservoirs and b) HIV disease progression.
描述(由申请人提供):概述:尽管有共识认为HIV加速合并感染(HIV+HCV+)患者的丙型肝炎(HCV)疾病,但关于HCV感染对HIV疾病进展的影响的研究存在差异。这项提案寻求继续支持我们的赠款HCV和艾滋病毒的进展和HAART应对妇女。在过去的5年中,我们发现HCV加速了HIV疾病的进展,这与双重病毒感染导致的免疫激活和T细胞成熟改变有关。我们的中心假设是,HIV疾病的进展受到HCV病毒动力学导致的CD 8活化增强和T细胞成熟改变的影响,并且HAART在持续HCV复制的情况下不会完全逆转这一点。具体目标:1)确定HCV在PBMC中的肝外复制、HCV动力学和合并感染HCV病毒血症妇女中的HIV疾病进展之间的关系。2)纵向研究T细胞活化/成熟和功能的关系,以及a)HCV准种动力学和肝外储库。B)疾病进展。3)评估PBMC中HCV储库和HCV准种动态与HIV病毒载量反应(VLR)和HAART后反弹的关系。4)确定免疫激活和T细胞成熟/功能与HIV VLR和HAART后反弹的关系,并与肝外复制和准种多样性相关。临床意义:我们的研究发现,与单一感染妇女相比,合并感染妇女:a)在从未有过CD 4计数< 200个细胞/mm 3的妇女中,发展为AIDS的概率几乎增加两倍; B)在较低的HIV RNA水平下,AIDS和死亡的相对危险性(RH)增加; c)与较高水平的活化CD 8 + T细胞相关的AIDS RH增加;他们还具有d)PBMC中HCV复制的40%流行率,其与酒精使用和先前的AIDS相关;和,e)活动性IDU中HCV准种的变化增加3倍。这些发现支持了我们的假设,即HCV动力学有助于免疫失调和艾滋病的发展以及艾滋病相关的死亡。合并感染的妇女可能需要在低于目前推荐的HIV RNA和高于目前推荐的CD 4计数阈值的情况下开始抗逆转录病毒治疗(ART),以预防艾滋病/死亡。考虑到与HIV疾病进展相关的许多临床、人口统计学和行为特征,需要一个大型队列。这项研究将使我们能够更好地确定那些可能从更积极的ART中受益的人。在这项研究中,我们将确定PBMC中肝外HCV复制、HCV动力学和a)HIV疾病进展之间的关系; B)来自妇女机构间HIV研究的HIV感染和HIV和HCV共感染妇女对HAART的长期反应。此外,我们将纵向研究T细胞活化/成熟和功能与a)HCV准种动力学和肝外储库和B)HIV疾病进展的关系。

项目成果

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Andrea A.Z. Kovacs其他文献

Andrea A.Z. Kovacs的其他文献

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{{ truncateString('Andrea A.Z. Kovacs', 18)}}的其他基金

Long-term Effects of IDU, HIV, HCV and the Impact of HCV Cure on Immune Activation and Liver Fibrosis in Aging Women
IDU、HIV、HCV 的长期影响以及 HCV 治愈对老年女性免疫激活和肝纤维化的影响
  • 批准号:
    9355485
  • 财政年份:
    2017
  • 资助金额:
    $ 7.41万
  • 项目类别:
HCV and HIV Progression in Women on HAART
接受 HAART 治疗的女性 HCV 和 HIV 进展情况
  • 批准号:
    8143231
  • 财政年份:
    2010
  • 资助金额:
    $ 7.41万
  • 项目类别:
AN OPEN-LABEL STUDY OF A ONCE DAILY DOSE OF EMTRICITABINE IN COMBINATION WITH
每日一次剂量的恩曲他滨与以下药物联合的开放标签研究
  • 批准号:
    7368197
  • 财政年份:
    2005
  • 资助金额:
    $ 7.41万
  • 项目类别:
AN OPEN-LABEL STUDY OF A ONCE DAILY DOSE OF EMTRICITABINE IN COMBINATION WITH
每日一次剂量的恩曲他滨与以下药物联用的开放标签研究
  • 批准号:
    7200000
  • 财政年份:
    2004
  • 资助金额:
    $ 7.41万
  • 项目类别:
PREVALENCE OF MORPHOLOGIC AND METABOLIC ABNORMALITIES IN HIV INFECTED
HIV 感染者形态和代谢异常的患病率
  • 批准号:
    7200032
  • 财政年份:
    2004
  • 资助金额:
    $ 7.41万
  • 项目类别:
ACTG 265: A PHASE I/II STUDY OF SAFETY & IMMUNOGENICITY OF LIVE-ATTENUATED
ACTG 265:I/II 期安全性研究
  • 批准号:
    7199983
  • 财政年份:
    2004
  • 资助金额:
    $ 7.41万
  • 项目类别:
ACTG 265: A PHASE I/II STUDY OF SAFETY & IMMUNOGENICITY OF LIVE-ATTENUATED
ACTG 265:I/II 期安全性研究
  • 批准号:
    7040145
  • 财政年份:
    2003
  • 资助金额:
    $ 7.41万
  • 项目类别:
OPEN-LABEL STUDY OF A ONCE DAILY DOSE OF EMTRICITABINE
每日一次剂量恩曲他滨的开放标签研究
  • 批准号:
    7040170
  • 财政年份:
    2003
  • 资助金额:
    $ 7.41万
  • 项目类别:
HCV and Progression of HIV and HAART Response in Women
女性 HCV 和 HIV 进展以及 HAART 反应
  • 批准号:
    6892041
  • 财政年份:
    2002
  • 资助金额:
    $ 7.41万
  • 项目类别:
HCV and Progression of HIV and HAART Response in Women
女性 HCV 和 HIV 进展以及 HAART 反应
  • 批准号:
    6627831
  • 财政年份:
    2002
  • 资助金额:
    $ 7.41万
  • 项目类别:

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