Department of Neurology, Washington University in St. Louis, St. Louis, MO.
Department of Neuroscience, Temple University, Philadelphia, PA.
J Acquir Immune Defic Syndr. 2020 Oct 1;85(2):244-251. doi: 10.1097/QAI.0000000000002435.
Despite combined antiretroviral therapy, neuroinflammation may persist in persons living with HIV (PLWH) and contribute to cognitive impairment in this population. Positron emission tomography (PET) imaging targeting 18 kDa translocator protein (TSPO) has been used to localize neuroinflammation. We aimed to use TSPO-PET imaging to evaluate neuroinflammation in PLWH.
Twenty-four virologically suppressed PLWH on combined antiretroviral therapy and 13 HIV-negative (HIV-) controls completed TSPO-PET imaging using the radiotracer [C]PBR28. Because of tracer complexity and differing procedures used in previous studies, we employed an expansive methodological approach, using binding potential (BP) and standard uptake value ratio and multiple different reference regions to estimate [C]PBR28 binding.
[C]PBR28 binding was measured in 30 cortical and subcortical regions and compared between PLWH and HIV- controls. Pearson correlation evaluated the association between [C]PBR28 binding and cognition and clinical measures of HIV.
Analyses conducted using multiple reference regions and measures of tracer uptake revealed no significant differences between [C]PBR28 binding in PLWH compared with HIV- controls. In addition, [C]PBR28 binding in PLWH was not significantly associated with clinical measures of HIV or plasma biomarkers of inflammation. [C]PBR28 binding was not significantly elevated in cognitively impaired PLWH compared with unimpaired PLWH, but there were inverse relationships between cognitive performance (executive and global function) and [C]PBR28 binding in PLWH.
Our results suggest that neuroinflammation may play a role in cognitive deficits, but overall neuroinflammatory levels as measured by TSPO-PET imaging in PLWH are not significantly different from those seen in HIV- controls.
尽管采用了联合抗逆转录病毒疗法，HIV 感染者（PLWH）仍可能存在神经炎症，并导致该人群认知障碍。正电子发射断层扫描（PET）成像靶向 18 kDa 转位蛋白（TSPO）已被用于定位神经炎症。我们旨在使用 TSPO-PET 成像来评估 PLWH 的神经炎症。
24 名病毒学上得到抑制的、正在接受联合抗逆转录病毒治疗的 PLWH 和 13 名 HIV- 对照者完成了使用放射性示踪剂 [C]PBR28 的 TSPO-PET 成像。由于示踪剂的复杂性和以前研究中使用的不同程序，我们采用了广泛的方法学方法，使用结合潜力（BP）和标准摄取值比以及多个不同的参考区域来估计 [C]PBR28 结合。
在 30 个皮质和皮质下区域测量 [C]PBR28 结合，并在 PLWH 和 HIV- 对照组之间进行比较。Pearson 相关性评估了 [C]PBR28 结合与认知和 HIV 的临床测量之间的关联。
使用多个参考区域和示踪剂摄取的测量方法进行的分析显示，PLWH 与 HIV- 对照组之间 [C]PBR28 结合没有显著差异。此外，PLWH 中的 [C]PBR28 结合与 HIV 的临床测量或炎症的血浆生物标志物没有显著相关。与认知正常的 PLWH 相比，认知受损的 PLWH 中 [C]PBR28 结合没有显著升高，但 PLWH 的认知表现（执行和整体功能）与 [C]PBR28 结合呈负相关。
我们的结果表明，神经炎症可能在认知缺陷中起作用，但 PLWH 中 TSPO-PET 成像测量的总体神经炎症水平与 HIV- 对照组没有显著差异。
