PLASMA VIRAL LOAD AND COGNITIVE DECLINE IN ADVANCED HIV INFECTION

血浆HIV-1RNA水平是预测长期临床症状的最佳指标 结果、死亡率和对抗逆转录病毒药物的反应，但预后 这些标记物对神经认知结果的价值尚不清楚。如果一个 降低全身性病毒负担可以逆转或稳定神经认知 损害[轻微认知/运动障碍(艾滋病毒-mcmd)和艾滋病毒痴呆 (艾滋病毒-D)]这将对20%的 最终将发展为HIV-D的艾滋病患者。此外，如果 神经认知损害的潜在可逆性是通过 降低血浆病毒载量，然后积极治疗HIV-MCMD可能 是有根据的。在横截面和纵向分析中，我们将 确定血浆HIV-1RNA水平是否与 特定的神经学、神经心理学、精神病学和功能性 460例晚期HIV感染者队列中的异常 每隔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是否 负载与HIV-mcmd和HIV-D的发病以及 无损害、HIV-mcmd和HIV-D阶段。纵向分析 将包括对重复结果的分析(一般估计 方程)、事件间隔时间分析(COX模型)和过渡分析 (马尔科夫主席分析)。在类似的分析中，我们将确定血浆 免疫激活标志物(β2-微球蛋白、肿瘤坏死因子α、肿瘤坏死因子受体2、可溶性细胞间黏附分子- 1)与神经认知障碍独立相关。组合 对敏感分子进行仔细的自然历史研究 化验将有助于更好地了解血浆病毒载量 测量可以用来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.