Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy
Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy
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DOI：
10.1212/wnl.0b013e3181ab2b3b
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发表时间：
2009-08-01
期刊：
影响因子：
9.9
通讯作者：
Ellis, R. J.
中科院分区：
文献类型：
--
作者：
Cysique, L. A.;Vaida, F.;Ellis, R. J.
目的：严格评估一组患有艾滋病相关神经认知障碍（HAND）并开始联合抗逆转录病毒治疗（CART）的个体认知变化的时间进程，并研究哪些人口统计学、实验室及治疗因素与神经心理学（NP）结果（或“任何NP改善”）相关。
方法：研究参与者包括37名患有轻度至中度NP损伤的HIV阳性个体，他们开始CART治疗，并在此后12、24、36和48周接受NP测试。使用基于回归的变化分数评估NP变化，该分数以一个单独的NP稳定组为参照进行标准化，从而控制向均数回归和练习效应。采用调整失访情况的混合效应回归模型来评估认知变化的时间进程及其与基线和随时间变化的预测因素的关联。
结果：在开始CART治疗的HAND患者中，认知改善在治疗开始后不久就会出现（12周时为13%），但更常见于治疗开始后24、36周以及直至48周（高达41%），只有不到5%的患者出现明显恶化。在多变量分析中，NP改善的独特预测因素包括更严重的基线NP损伤和更高的CART中枢神经系统穿透指数。病毒载量更大幅度的降低仅在单变量分析中与NP改善相关。
结论：具有临床意义的神经心理学改善似乎在联合抗逆转录病毒治疗开始后24 - 36周左右达到峰值，并在1年的研究期间持续存在。这项研究还提供了新的证据，即选择能在中枢神经系统达到治疗浓度的抗逆转录病毒药物可能使疗效最大化。《神经病学》2009年；73卷：342 - 348页
Objective: To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement").Methods: Study participants included 37 HIV + individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors.Results: In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses.Conclusion: Clinically meaningful neuropsychological improvement seemed to peak around 24-36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS. Neurology (R) 2009; 73: 342-348