Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.
Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.
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DOI：
10.1097/qai.0000000000002484
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发表时间：
2020-12-15
期刊：
影响因子：
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通讯作者：
Letendre SL
中科院分区：
文献类型：
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作者：
Anderson AM;Jang JH;Easley KA;Fuchs D;Gisslen M;Zetterberg H;Blennow K;Ellis RJ;Franklin D;Heaton RK;Grant I;Letendre SL
在许多情况下，缺乏病毒学控制仍然是常见的艾滋病毒感染者（PWH）由于晚介绍和缺乏保留在照顾。这有助于神经元损伤和神经认知障碍，这仍然很普遍。需要更多的证据来了解PWH和没有艾滋病毒的人（PWOH）的这些结果。我们在美国的两个地点招募了开始抗逆转录病毒治疗（ART）的PWH和PWOH。入组了108名成人（56名PWOH和52名PWH），其中大多数在至少24周后进行了第二次评估（共193次评估）。测定血浆和脑脊液（CSF）中的肿瘤坏死因子α（TNFα）、单核细胞趋化蛋白-1（MCP-1）、新蝶呤、可溶性CD 14和神经丝轻链蛋白（NFL）。使用包括贝叶斯模型平均（BMA）在内的多变量模型，我们分析了基线和随时间推移与整体神经心理学（NP）表现（NPT-9）和CSF NFL相关的因素。基线时，较高的CSF MCP-1和血浆sCD 14与PWH中较差的NPT-9相关，而CSF HIV RNA降低是随时间推移与改善的NPT-9相关的唯一标志物。在PWH中，较高的CSF新蝶呤与较高的NFL最密切相关。在PWOH中，更高的CSF MCP-1与更高的NFL最密切相关。在ART开始后，CSF MCP-1的降低与NFL降低最密切相关。单核细胞相关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是否可以改善HIV相关的神经行为疾病。
Across many settings, lack of virologic control remains common in people with HIV (PWH) due to late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remain prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). We recruited PWH initiating antiretroviral therapy (ART) as well as PWOH at two sites in the United States. 108 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 (TNFα), 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 (BMA), we analyzed factors associated with global neuropsychological (NP) performance (NPT-9) and CSF NFL at baseline and over time. 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. Following ART initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease. Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate if therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.