Immunologic Profiles of Distinct Cognitive Trajectories in Adultswith Perinatal HIV

围产期 HIV 感染者的不同认知轨迹的免疫学特征

基本信息

  • 批准号:
    10450059
  • 负责人:
  • 金额:
    $ 16.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-11 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Over 60,000 young adults are living with HIV in the US today, many of whom acquired HIV at birth. This group of adults with perinatally acquired HIV (pHIV) has not seen improvements in the prevalence of HIV- related co-morbidities, including poor cognitive outcomes. Despite this trend, little is known about the prognosis and pathogenesis of pHIV-related cognitive impairment in adulthood. Cognitive dysfunction occurs in up to half of individuals living with HIV, and is directly associated with immune activation in adults with horizontally acquired HIV (hHIV). In contrast, CD8+ T-cell and monocyte activation in our cohort of children with pHIV in Southeast Asia correlates with better cognitive scores suggesting an adapted immune-host response in those who are long-term survivors of pHIV. This adapted state has not been well studied. The goal of our proposed study is to address key gaps in our understanding of 1) cognitive trajectories and 2) biomarkers of cognitive resilience in adults with pHIV, through a recently initiated longitudinal cohort study of adults with pHIV in Connecticut. We will evaluate 1) cognitive performance and 2) interactions between peripheral and cerebrospinal fluid (CSF) immunologic markers, neuroimaging and cognition using a novel analytic method, group based trajectory modeling. This study will determine the prognosis of cognitive impairment and further characterize the biologic underpinnings of cognitive resilience as potential neuroprotective targets in adults with pHIV. The candidate is a pediatric neurologist with specialized training in neuro-infectious diseases. Dr. Patel is committed to improving our understanding of the pathogenesis of and treatment for poor neurologic outcomes following pHIV. The proposal will capitalize on Dr. Patel's prior training and mentored research experience in group based trajectory analysis of longitudinal cognitive data in children with pHIV, while enabling her to build expertise in 1) flow cytometry methods and analyses, 2) utilizing diffusion tensor imaging as a research tool, and 3) dual trajectory analysis, a complex modeling technique to assess contemporaneous changes in longitudinally acquired biomarker and cognitive data. Dr. Patel has assembled a mentorship committee comprised of leaders in the pathogenesis of neurologic injury in adults with hHIV (Serena Spudich, MD, primary mentor), biomarkers of disease progression in pHIV (Elijah Paintsil, MBChB, co-mentor), and biostatistics and imaging markers of cognitive impairment in pHIV (Robert Paul, PhD, co-mentor). The knowledge and experience gained from this proposal will allow Dr. Patel to successfully compete for R01 funding to further evaluate the pathogenesis and prevention of pHIV-related neurologic morbidity. Her future R01 applications will focus on cerebral HIV compartmentalization in adults with pHIV and analyzing cellular subsets identified in the proposed study as linked to cognitive resilience in CSF using mass cytometry.
今天,美国有超过6万名年轻人携带艾滋病毒,其中许多人在出生时就感染了艾滋病毒。 这组携带围产期获得性艾滋病毒(PHIV)的成年人在 与艾滋病毒相关的共病,包括认知结果不佳。尽管有这种趋势,但人们对 PHIV相关认知功能障碍的成年期预后及发病机制。认知功能障碍 在多达一半的艾滋病毒携带者中发生,并与 成人水平获得性艾滋病毒(HHIV)。相比之下,CD8+T细胞和单核细胞在我们的 东南亚pHIV携带者的队列与较好的认知得分相关,这表明 PHIV长期幸存者的适应性免疫宿主反应。这种适应状态并没有 已经做了很好的研究。我们提议的研究的目标是解决我们对 1)成人pHIV感染者的认知轨迹和2)认知弹性的生物标记物,通过 最近在康涅狄格州启动了对成年pHIV感染者的纵向队列研究。我们将评估1) 认知表现和2)外周和脑脊液免疫之间的相互作用 标记物,神经成像和认知使用一种新的分析方法,基于群体的轨迹建模。 本研究将确定认知障碍的预后,并进一步描述其生物学特征。 认知复原力作为pHIV成人潜在神经保护靶点的基础。 应聘者是一名接受过神经感染性疾病专业培训的儿科神经科医生。Dr。 帕特尔致力于提高我们对贫困的发病机制和治疗的理解。 PHIV感染后的神经学结果。该提案将利用帕特尔博士之前的培训和 在基于群体的纵向认知数据轨迹分析中的指导性研究经验 ,同时使她能够积累1)流式细胞仪方法和 分析,2)利用扩散张量成像作为研究工具,以及3)双轨迹分析,a 用复杂的建模技术评估纵向获得者的同期变化 生物标志物和认知数据。帕特尔博士组建了一个由领导人组成的指导委员会 在成人艾滋病毒感染者神经损伤的发病机制中(Serena Spudich,医学博士,主要导师), PHIV疾病进展的生物标记物(Elijah Paintsil,MBCHB,共同导师),以及生物统计和 PHIV认知损害的成像标记物(罗伯特·保罗博士,共同导师)。这些知识和知识 从这项提案中获得的经验将使Patel博士能够成功地竞争R01资金 进一步探讨pHIV相关神经系统疾病的发病机制及预防。她的未来R01 应用将集中在成人pHIV感染者的脑HIV分区和分析细胞 在拟议的研究中,利用质量细胞术确定了与脑脊液中认知弹性有关的亚群。

项目成果

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Payal Patel其他文献

Payal Patel的其他文献

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{{ truncateString('Payal Patel', 18)}}的其他基金

Myelin Content and Cognitive Trajectories in Young Adults Living with Virally Suppressed HIV
感染病毒抑制的艾滋病毒的年轻人的髓磷脂含量和认知轨迹
  • 批准号:
    10759305
  • 财政年份:
    2023
  • 资助金额:
    $ 16.91万
  • 项目类别:
Immunologic Profiles of Distinct Cognitive Trajectories in Adultswith Perinatal HIV
围产期 HIV 感染者的不同认知轨迹的免疫学特征
  • 批准号:
    10657484
  • 财政年份:
    2019
  • 资助金额:
    $ 16.91万
  • 项目类别:
Immunologic Profiles of Distinct Cognitive Trajectories in Adultswith Perinatal HIV
围产期 HIV 感染者的不同认知轨迹的免疫学特征
  • 批准号:
    10206044
  • 财政年份:
    2019
  • 资助金额:
    $ 16.91万
  • 项目类别:
Immunologic Profiles of Distinct Cognitive Trajectories in Adults with Perinatal HIV
围产期艾滋病毒成人独特认知轨迹的免疫学特征
  • 批准号:
    10190661
  • 财政年份:
    2019
  • 资助金额:
    $ 16.91万
  • 项目类别:

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