Human Metabolomics, North-West University, Potchefstroom, South Africa.
Department of Psychiatry and Mental Health, Brain Behaviour Unit, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa; SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
J Neuroimmunol. 2021 Sep 15;358:577649. doi: 10.1016/j.jneuroim.2021.577649. Epub 2021 Jun 30.
HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Multiple cerebrospinal fluid (CSF) immune markers have been studied but it is unclear which markers most consistently correlate with neurocognitive impairment. We therefore conducted a systematic review of studies of the association of CSF immune markers with neurocognitive performance in ART-experienced PLWH. We aimed to synthesize the published data to determine consistent findings and to indicate the most noteworthy CSF markers of HAND. Twenty-nine studies were included, with 20 cross-sectional studies and 9 longitudinal studies. From the group of markers most often assayed, specific monocyte activation (higher levels of Neopterin, sCD163, sCD14) and neuroinflammatory markers (higher levels of IFN-γ, IL-1α, IL-7, IL-8, sTNFR-II and lower levels of IL-6) showed a consistent direction in association with HIV-associated neurocognitive impairment. Furthermore, significant differences exist in CSF immune markers between HIV-positive people with and without neurocognitive impairment, regardless of viral load and nadir/current CD4 count. These markers may be useful in furthering our understanding of the neuropathology, diagnosis and prognosis of HAND. Studies using prospective designs (i.e. pre- and post-interventions), "multi-modal" methods (e.g. imaging, inflammation and neurocognitive evaluations) and utilizing a combination of the markers most commonly associated with HAND may help delineate the mechanisms of HAND.
HIV-1 可引发一系列认知障碍，即 HIV 相关神经认知障碍 (HAND)。在抗逆转录病毒疗法 (ART) 时代，尽管病毒载量低或无法检测到，但 HAND 在 HIV 感染者 (PLWH) 中仍然普遍存在。持续性神经炎症可能在促成生物学机制中发挥重要作用。已经研究了多种脑脊液 (CSF) 免疫标志物，但尚不清楚哪些标志物与神经认知障碍最一致相关。因此，我们对 CSF 免疫标志物与 ART 经验丰富的 PLWH 神经认知表现相关性的研究进行了系统综述。我们旨在综合已发表的数据，以确定一致的发现，并指出 HAND 最值得注意的 CSF 标志物。共纳入 29 项研究，其中 20 项为横断面研究，9 项为纵向研究。在经常检测的标志物组中，单核细胞活化的特定标志物（较高水平的 Neopterin、sCD163、sCD14）和神经炎症标志物（较高水平的 IFN-γ、IL-1α、IL-7、IL-8、sTNFR-II 和较低水平的 IL-6）与 HIV 相关神经认知障碍的相关性呈一致方向。此外，无论病毒载量和 CD4 计数的最低点/当前值如何，HIV 阳性人群中 CSF 免疫标志物在有无神经认知障碍者之间存在显著差异。这些标志物可能有助于进一步了解 HAND 的神经病理学、诊断和预后。使用前瞻性设计（即干预前后）、“多模态”方法（如影像学、炎症和神经认知评估）以及利用与 HAND 最常相关的标志物组合的研究可能有助于描绘 HAND 的机制。
