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: 6617737
• 负责人: LEON G EPSTEIN
• 金额: $ 10万
• 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 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617737
• 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， 系统性疾病进展和抗逆转录病毒应答的预测因子 疗法血浆和脑脊液中HIV水平对急性脑梗死患者的预后价值 神经功能衰退还没有得到很好的研究。这可能是特别 在一个有效的联合抗逆转录病毒治疗的时代， 存在完全系统抑制HIV的潜力， 大脑隔离和持续复制。HIV引起的神经损伤 由活化的巨噬细胞/小胶质细胞的产物介导。我们之前 建立了一个由273名HIV感染者组成的队列， 神经认知异常，利用达纳财团，包括 来自3个机构的研究者：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 最大的，最多民族，种族和性别多样化的群体聚集， 研究神经功能缺损的日期。我们建议： 受试者以维持200例受试者的队列（N=460，5年）。 项目1（CU）将进行横向和纵向分析， 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-1）独立相关。 MCMD）或HIV痴呆（HIV-D）。项目2（JHU）将侧重于 CSF HIV水平对神经功能衰退的预后意义，以及 检查艾滋病毒水平和免疫标志物之间的关系， 在血浆、CSF和脑中活化。项目3（CU）将确定 艾滋病毒水平、免疫激活和严重程度之间的关系 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）和免疫活化标志物的测定 所有三个项目的资金将集中在核心B（JHU）。该PPG 建立在达纳财团的现有基础设施上， 具有实现研究目标的能力。的 调查人员为具体项目提供补充专业知识。 这一多样化的晚期HIV感染受试者队列提供了一个 独特的机会来调查病毒载量之间的关系， 免疫激活和HIV感染过程中神经功能障碍的进展 感染