NEUROCOGNITIVE FUNCTION, HIV LOAD AND SURROGATE MARKERS

神经认知功能、HIV 载量和替代标志物

• 批准号: 6351845
• 负责人: LEON G EPSTEIN
• 金额: $ 121.94万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351845
• 关键词: AIDS /HIV neuropathy; behavioral /social science research tag; biomarker; cognition disorders; human immunodeficiency virus 1; virus load

Quantitative assessment of plasma HIV load (RNA copy number) is a powerful predictor of systemic disease progression and response to anti-retroviral therapy. The prognostic value of HIV levels in plasma and CSF for neurologic decline have not been well studied. This may be particularly relevant in an era of potent combination antiretroviral therapy, where the potential exists for complete systemic suppression of HIV, with perhaps brain sequestration and persistent replication. HIV induced neural damage is mediated by products of activated macrophages/microglia. We previously established a cohort of 273 HIV infected subjects, with, or at risk for, neurocognitive abnormalities, utilizing the Dana Consortium, consisting of investigators from 3 institutions: The University of Rochester(UR), Columbia University(CU) and John Hopkins University(JHU). This is the largest, most ethnically, racially and gender diverse cohort assembled to date to study neurologic impairment. We propose: to recruit additional subjects to maintain a cohort of 200 subjects (N=460 over 5 years). Project 1 (CU) will perform cross=sectional and longitudinal analysis to determine if plasma HIV levels and markers of immune activation are independently associated with HIV minor cognitive/motor disorder (HIV- MCMD) or HIV Dementia (HIV-D). Project 2 (JHU) will focus on the prognostic significance of CSF HIV levels for neurologic decline, and examine the relationship between HIV levels and markers of immune activation in plasma, CSF and brain. Project 3 (CU) will determine the relationship between HIV levels, immune activation and severity of functional impairment (neurologic and psychiatric). Core A (UR) will provide administrative functions, data management and biostatistics support. Assays of HIV load (NASBA) and for markers of immune activation for all three projects will be centralized at Core B (JHU). This PPG builds on the existing infrastructure of the Dana Consortium, a consortium with a demonstrated ability to achieve research objectives. The investigators provide complementary expertise for site specific projects. This diverse cohort of subjects with advanced HIV infection provides a unique opportunity to investigate the relationship between virus load, immune activation and the progression of neurologic dysfunction during HIV infection.

定量评估血浆HIV载量(RNA拷贝数)是一种强有力的方法 全身性疾病进展和抗逆转录病毒反应的预测因子 心理治疗。血浆和脑脊液中HIV水平对急性脑出血患者预后的预测价值 神经功能衰退还没有得到很好的研究。这可能是特别的 在一个强有力的联合抗逆转录病毒治疗的时代， 存在着完全系统性地抑制艾滋病毒的潜力，可能 大脑隔离和持续复制。HIV引起的神经损伤 是由激活的巨噬细胞/小胶质细胞的产物介导的。我们之前 建立了一个由273名艾滋病毒感染者组成的队列， 神经认知异常，利用达纳联盟，由以下组成 来自3个机构的调查人员：罗切斯特大学(UR)， 哥伦比亚大学(CU)和约翰·霍普金斯大学(JHU)。这是 最大、最具种族、种族和性别多样性的队列聚集在一起 研究神经损伤的日期。我们建议：招聘更多 受试者维持200名受试者(5年内N=460人)。 项目1(CU)将执行横截面和纵向分析 确定血浆HIV水平和免疫激活标志物是否 与HIV轻度认知/运动障碍(HIV- Mcmd)或HIV痴呆(HIV-D)。项目2(JHU)将重点放在 脑脊液HIV水平对神经功能下降的预后意义 探讨HIV水平与免疫标志物的关系 血浆、脑脊液和脑组织中的激活。项目3(CU)将决定 人类免疫缺陷病毒水平、免疫激活与急性脑炎严重程度的关系 功能障碍(神经和精神)。核心A(UR)将 提供行政职能、数据管理和生物统计 支持。HIV载量(NASBA)和免疫激活标志物的检测 所有三个项目都将集中在核心B(JHU)。这个PPG 建立在达纳财团的现有基础设施上，该财团是一个 具有实现研究目标的证明能力。这个 调查人员为现场具体项目提供补充专业知识。 这种不同的晚期艾滋病毒感染受试者队列提供了 独一无二的机会调查病毒载量与 HIV免疫激活与神经功能障碍的进展 感染。