NEUROCOGNITIVE FUNCTION, HIV LOAD AND SURROGATE MARKERS

血浆 HIV 载量（RNA 拷贝数）的定量评估是一个强大的工具 全身性疾病进展和抗逆转录病毒反应的预测因子 治疗。血浆和脑脊液中 HIV 水平的预后价值 神经功能衰退尚未得到充分研究。这可能特别 与有效的联合抗逆转录病毒疗法的时代相关，其中 存在完全系统性抑制艾滋病毒的潜力，也许 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，这些受试者患有或有风险： 神经认知异常，利用达纳联盟，包括 来自 3 个机构的研究人员：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 规模最大、种族、种族和性别最多样化的群体聚集在一起 研究神经功能障碍的日期。我们建议：增聘 受试者维持一个由 200 名受试者组成的队列（5 年内 N=460）。 项目 1 (CU) 将进行横断面和纵向分析 确定血浆 HIV 水平和免疫激活标志物是否 与 HIV 轻微认知/运动障碍（HIV- MCMD）或艾滋病毒痴呆症（HIV-D）。项目 2 (JHU) 将重点关注 CSF HIV 水平对神经功能衰退的预后意义，以及 检查 HIV 水平与免疫标志物之间的关系 血浆、脑脊液和大脑中的激活。项目 3 (CU) 将确定 HIV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 提供管理功能、数据管理和生物统计 支持。 HIV 载量测定 (NASBA) 和免疫激活标记物 所有三个项目都将集中在 Core B (JHU)。这个PPG 建立在 Dana Consortium 联盟的现有基础设施之上 具有实现研究目标的能力。的 研究人员为特定地点的项目提供补充专业知识。 这个不同的晚期 HIV 感染受试者群体提供了 调查病毒载量之间关系的独特机会， HIV期间的免疫激活和神经功能障碍的进展 感染。

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.