Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline
Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline
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DOI：
10.1212/wnl.0000000000000492
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发表时间：
2014-06-10
期刊：
影响因子：
9.9
通讯作者：
Heaton, Robert K.
中科院分区：
文献类型：
--
作者：
Grant, Igor;Franklin, Donald R., Jr.;Heaton, Robert K.
目的：尽管联合抗逆转录病毒治疗（CART）仍然普遍存在hiv相关神经认知障碍（HAND），但最常见的HAND诊断——无症状神经认知障碍（ANI）的临床相关性尚不清楚。我们调查了患有ANI的hiv感染者是否比神经认知正常（NCN）的人更有可能经历日常功能下降（症状性下降）。方法：来自CNS HIV抗逆转录病毒治疗效应研究（CHARTER）队列的347名人类参与者在基线时为NCN （n = 226）或ANI （n = 121）。神经认知评估大约每6个月进行一次，中位（四分位间距）随访45.2（28.7-63.7）个月。症状性下降是基于自我报告（SR）或客观的、基于表现的（PB）日常功能问题。在调整基线和时间相关协变量（包括CD41 t淋巴细胞计数（CD4）、病毒学抑制、CART和情绪）后，使用比例风险模型生成进展为症状性HAND的风险比。结果：在调整基线预测因子后，ANI组出现症状性HAND的时间比NCN短：症状性HAND的调整风险比SR为2.0（可信区间[CI] 1.1-3.6; p = 0.02）， PB为5.8 (CI 3.2-10.7; p < 0.0001)， SR或PB均为3.2 （CI 2.0-5.0; p < 0.0001）。当前CD4和抑郁是显著的时间依赖性协变量，但抗逆转录病毒治疗方案、病毒学抑制和药物滥用或依赖不是。结论：这项纵向研究表明，ANI传达了早期发展为症状性HAND的风险增加2至6倍，支持ANI诊断在临床环境中的预后价值。识别出那些症状性衰退风险最高的患者，可能为调整治疗方案以延缓病情发展提供机会。
Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline).Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD41 T-lymphocyte count (CD4), virologic suppression, CART, and mood.Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not.Conclusions: This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.