PLASMA VIRAL LOAD AND COGNITIVE DECLINE IN ADVANCED HIV INFECTION

血浆HIV-1 RNA水平是长期临床感染的最佳预测因子。 结果、死亡率和抗逆转录病毒治疗的反应，但预后 这些标记物对神经认知结果的价值尚不清楚。如果 降低全身病毒负荷可以逆转或稳定神经认知功能 轻度认知/运动障碍（HIV-MCMD）和HIV痴呆 （HIV-D）]这将对20%的 艾滋病患者最终会发展为HIV-D。而且如果 神经认知障碍的潜在可逆性是通过以下途径介导的： 血浆病毒载量减少，那么HIV-MCMD的积极治疗可能 是有道理的在横向和纵向分析中，我们将 确定血浆HIV-1 RNA水平是否与 具体神经学、神经心理学、精神病学和功能学 460名晚期HIV感染的男性和女性队列中的异常 每6个月在罗切斯特大学、哥伦比亚大学 和约翰霍普金斯大学。我们将确定病毒的变化 负荷量与HIV-MCMD和HIV-D的发病以及HIV-MCMD和HIV-D之间的转换有关。 无损伤期、HIV-MCMD期和HIV-D期。纵向分析 将包括重复结果的分析（广义估计 方程）、事件发生时间分析（考克斯模型）和转换分析 （Markov chair analyses）。在类似的分析中，我们将确定血浆是否 免疫活化标志物（β 2-微球蛋白、TNF α、TNFr 2、sICAM-1、TNF α、TNF 1)与神经认知障碍独立相关。结合 一项精心进行的自然史研究， 分析将导致更好地了解如何血浆病毒载量 测量可用于预测和监测神经认知结果。

Plasma HIV-1 RNA levels are the best predictors of long-term clinical outcome, mortality, and response to anti-retrovirals, but the prognostic value of these markers for neurocognitive outcomes is not known. If a reduction in systemic viral burden can reverse or stabilize neurocognitive impairment[minor cognitive/motor disorder (HIV-MCMD) and HIV dementia (HIV-D)] this would have tremendous treatment implications for the 20% of AIDS patients who will eventually develop HIV-D. Moreover, if the potential reversibility of neurocognitive impairment is mediated through a reduction in plasma viral load, then aggressive therapy of HIV-MCMD may be warranted. In both cross-sectional and longitudinal analyses, we will determine if plasma HIV-1 RNA levels are independently associated with specific neurological, neuropsychological, psychiatric and functional abnormalities in a cohort of 460 men and women with advanced HIV infection seen every 6 months at the University of Rochester, Columbia University and John Hopkins University. We will determine whether change in viral load is related to the onset of HIV-MCMD and HIV-D and transition among the stages of no impairment, HIV-MCMD, and HIV-D. Longitudinal analyses will include analyses of repeated outcomes (generalized estimating equations), time to event analyses (Cox models), and transition analyses (Markov chair analyses). In similar analyses, we will determine if plasma markers of immune activation (beta2-microglobulin, TNFalpha, TNFr2, sICAM- 1) are independently associated with neurocognitive impairment. Combining a carefully conducted natural history study with sensitive molecular assays will lead to a better understanding of how plasma viral load measures can be used to predict and monitor neurocognitive outcomes.