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认知与神经元:HIV 感染者与非感染者的纵向研究。

Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.

机构信息

Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA.

Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN.

出版信息

J Acquir Immune Defic Syndr. 2020 Dec 15;85(5):617-625. doi: 10.1097/QAI.0000000000002484.

Abstract

BACKGROUND

Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH).

METHODS

We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time.

RESULTS

At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease.

CONCLUSION

Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.

摘要

背景

由于艾滋病毒感染者(PWH)就诊较晚且未能持续接受治疗,其病毒学控制仍不理想,这在许多环境中都很常见。这导致神经元损伤和神经认知障碍仍然普遍存在。需要更多的证据来了解 PWH 和未感染艾滋病毒的人(PWOH)的这些结果。

方法

我们在美国的 2 个地点招募了开始接受抗逆转录病毒治疗的 PWH 和 PWOH。共有 108 名成年人入组(56 名 PWOH 和 52 名 PWH),其中大多数人在至少 24 周后进行了第二次评估(共 193 次评估)。在血浆和脑脊液(CSF)中测量了肿瘤坏死因子-α、单核细胞趋化蛋白-1(MCP-1)、新蝶呤、可溶性 CD14 和神经丝轻链蛋白(NFL)。使用包括贝叶斯模型平均在内的多变量模型,我们分析了与基线时和随时间变化的整体神经心理表现(NPT-9)和 CSF NFL 相关的因素。

结果

基线时,较高的 CSF MCP-1 和血浆 sCD14 与 PWH 的 NPT-9 较差相关,而 CSF HIV RNA 下降是唯一与随时间改善 NPT-9 相关的标志物。在 PWH 中,较高的 CSF 新蝶呤与较高的 NFL 最密切相关。在 PWOH 中,较高的 CSF MCP-1 与较高的 NFL 最密切相关。抗逆转录病毒治疗开始后,CSF MCP-1 的下降与 NFL 的下降最密切相关。

结论

单核细胞相关的 CSF 生物标志物与 PWH 和 PWOH 中的神经元损伤高度相关。需要更多的研究来评估针对单核细胞相关炎症的治疗方法是否可以改善 HIV 相关的神经行为疾病。

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