Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated, cerebrospinal, fluid levels of human immunodeficiency virus RNA
Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated, cerebrospinal, fluid levels of human immunodeficiency virus RNA
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DOI：
10.1001/archneur.59.6.923
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发表时间：
2002-06-01
影响因子：
--
通讯作者：
Grant, I
中科院分区：
文献类型：
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作者：
Ellis, RJ;Moore, DJ;Grant, I
工作背景：如果脑脊液（CSF）人类免疫缺陷病毒（HIV）RNA水平在神经心理学（NP）损害发展之前升高，则这种观察结果将支持对CSF HIV RNA水平的前瞻性监测以及旨在降低CSF HIV水平的治疗干预。目的：确定早期CSF HIV RNA水平升高是否预示HIV感染受试者随后进展为NP损伤。方法：我们在一项前瞻性队列研究中检查了139名受试者。在初始和随访访视时进行全面的NP、神经医学和实验室评价，间隔至少6个月。采用市售的基于聚合酶链反应的检测方法测定血浆和CSF中的人类免疫缺陷病毒RNA水平。为了评估我们研究结果的稳健性，我们以两种方式分析了NP性能随时间的变化。首先，我们使用全球NP性能的掩蔽临床评级来识别最初NP正常的个体，然后以类似的盲法确定这些受试者中哪些随后成为NP受损。第二，在一个单独的分析，我们评估了受试者的原始分数的变化对每一个一系列的NP测试措施之间的基线和follow-up.Results：在受试者谁是不受损的首次访问中，更高水平的HIV RNA在CSF显着预测全球NP减值进展在后续评估。脑脊液HIV RNA水平在预测NP损害进展方面优于其他临床和实验室指标。更高的CSF HIV RNA水平与注意力、学习和运动功能测试中的表现恶化相关。结论：由于CSF HIV RNA水平升高（大于或等于200拷贝/mL）可预测随后进展为NP损伤，因此，即使在腰椎穿刺时未发现损伤，监测CSF病毒载量和治疗以降低CSF HIV RNA水平也可能是临床上有必要的。
Background: If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels are elevated before the development of neuropsychological (NP) impairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeutic interventions designed to lower CSF HIV levels.Objective: To determine whether increased CSF HIV RNA levels at an earlier time predict subsequent progression to NP impairment in HIV-infected subjects.Methods: We examined 139 subjects in a prospective cohort study. Comprehensive NP, neuromedical, and laboratory evaluations were performed at initial and follow-up visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma and CSF were measured with a commercially available, polymerase chain reaction-based assay. To assess the robustness of our findings, we analyzed changes in NP performance over time in 2 ways. First, we used masked clinical ratings of global NP performance to identify individuals who were initially NP normal, and then determined, in a similarly blinded fashion, which of these subjects subsequently became NP impaired. Second, in a separate analysis, we assessed change in subjects' raw scores on each of a series of NP test measures between baseline and follow-up.Results: Among subjects who were not impaired at the initial visit, higher levels of HIV RNA in CSF significantly predicted progression to global NP impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels outperformed other clinical and laboratory measures in predicting progression to NP impairment. Higher CSF HIV RNA levels were associated with worsening performance on tests of attention, learning, and motor function.Conclusion: Because elevated CSF HIV RNA levels (greater than or equal to 200 copies/mL) predict subsequent progression to NP impairment, monitoring of CSF viral load and therapy to reduce CSF HIV RNA levels may be clinically warranted, even if impairment is not identified at the time of lumbar puncture.