Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health.
Laboratory of Immunoregulation, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
AIDS. 2021 Jul 1;35(8):1209-1219. doi: 10.1097/QAD.0000000000002875.
We evaluated brain glucose metabolism in people living with HIV (PWH) with [18F]-Fluoro-Deoxyglucose (FDG) PET/computed tomography (CT) before and after antiretroviral therapy (ART) initiation.
We conducted a longitudinal study wherein ART-naive late-presenting untreated PWH with CD4+ cell counts less than 100 cells/μl were prospectively assessed for FDG uptake at baseline and at 4-8 weeks (n = 22) and 19-26 months (n = 11) following ART initiation.
Relative uptake in the subcortical regions (caudate, putamen and thalamus) and cortical regions (frontal, parietal, temporal and occipital cortices) were compared across time and correlated with biomarkers of disease activity and inflammation, in addition to being compared with a group of uninfected individuals (n = 10).
Before treatment initiation, putaminal and caudate relative FDG uptake values in PWH were significantly higher than in uninfected controls. Relative putaminal and thalamic uptake significantly decreased shortly following ART initiation, while frontal cortex values significantly increased. FDG uptake changes correlated with changes in CD4+ cell counts and viral load, and, in the thalamus, with IL-6R and sCD14. Approximately 2 years following ART initiation, there was further decrease in subcortical relative uptake values, reaching levels below those of uninfected controls.
Our findings support pretreatment basal ganglia and thalamic neuroinflammatory changes in PWH, which decrease after treatment with eventual unmasking of long-term irreversible neuronal damage. Meanwhile, increased frontal cortex metabolism following ART initiation suggests reversible cortical dysfunction which improves with virologic control and increased CD4+ cell counts. Early initiation of treatment after HIV diagnosis and secondary control of inflammation are thus necessary to halt neurological damage in PWH.
我们使用 [18F]-氟代脱氧葡萄糖（FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）评估了开始抗逆转录病毒治疗（ART）前后艾滋病毒（HIV）感染者（PWH）的脑葡萄糖代谢。
我们进行了一项纵向研究，前瞻性评估了 CD4+细胞计数小于 100 个/μl 的晚期未经治疗的 ART 初治 PWH 的 FDG 摄取，在开始 ART 前（n=22）和 4-8 周（n=22）及 19-26 个月（n=11）时进行评估。
比较了皮质区（额叶、顶叶、颞叶和枕叶）和皮质下区（尾状核、壳核和丘脑）的相对摄取，并与疾病活动和炎症的生物标志物相关，同时与一组未感染个体（n=10）进行比较。
在开始治疗前，PWH 的壳核和尾状核相对 FDG 摄取值明显高于未感染对照者。ART 开始后不久，壳核和丘脑的相对摄取值显著降低，而额叶皮质值显著增加。FDG 摄取的变化与 CD4+细胞计数和病毒载量的变化相关，在丘脑与白细胞介素-6 受体（IL-6R）和可溶性 CD14 相关。开始 ART 约 2 年后，皮质下相对摄取值进一步下降，达到低于未感染对照者的水平。
我们的研究结果支持 PWH 治疗前基底节和丘脑神经炎症变化，治疗后这些变化减少，最终暴露出长期不可逆的神经元损伤。与此同时，ART 开始后额叶皮质代谢增加表明皮质功能可逆性障碍，随着病毒学控制和 CD4+细胞计数增加而改善。因此，HIV 诊断后早期开始治疗和二级控制炎症对于阻止 PWH 的神经损伤是必要的。
