Department of Imaging Sciences, University of Rochester Medical Center, Rochester NY, USA; Department of Neuroscience, University of Rochester Medical Center, Rochester NY, USA.
Department of Electrical and Computer Engineering, University of Rochester, Rochester, USA.
Neuroimage Clin. 2021;31:102693. doi: 10.1016/j.nicl.2021.102693. Epub 2021 May 7.
The aim of this study was to quantify, via Magnetic Resonance Spectroscopy (MRS), the effect of combination antiretroviral therapy (cART) on brain metabolites and characterize any possible associations between changes in metabolites, age, blood biomarkers of neuronal damage, functional connectivity and cognitive performance. As cART has dramatically increased the life expectancy of HIV-infected (HIV + ) individuals and unmasked an increase in HIV-associated neurocognitive disorders, it is still not clear whether cART neurotoxicity contributes to these disorders. We hypothesized a bimodal effect, with early cART treatment of HIV infection decreasing inflammation as measured by MRS metabolites and improving cognitive performance, and chronic exposure to cART contributing to persistence of cognitive impairment via its effect on mitochondrial function. Basal ganglia metabolites, functional connectivity, cognitive scores, as well as plasma levels of neurofilament light chain (NfL) and tau protein were measured before and after 12 weeks, 1 year and 2 years of cART in a cohort of 50 cART-naïve HIV + subjects and 72 age matched HIV- healthy controls. Glutamate (Glu) levels were lower in the cART naïve patients than in healthy controls and were inversely correlated with plasma levels of NfL. There were no other significant metabolite differences between HIV + and uninfected individuals. Treatment improved Glu levels in HIV+, however, no associations were found between Glu, functional connectivity and cognitive performance. Stable brain metabolites and plasma levels of NfL and Tau over two-years of follow-ups suggest there are no signs of cART neurotoxicity in this relatively young cohort of HIV + individuals.
本研究旨在通过磁共振波谱（MRS）定量评估联合抗逆转录病毒治疗（cART）对脑代谢物的影响，并描述代谢物变化与年龄、神经元损伤的血液生物标志物、功能连接和认知表现之间的任何可能关联。由于 cART 极大地延长了 HIV 感染（HIV + ）个体的预期寿命，并揭示了 HIV 相关神经认知障碍的增加，因此仍不清楚 cART 神经毒性是否导致这些障碍。我们假设存在双峰效应，即 HIV 感染的早期 cART 治疗通过 MRS 代谢物降低炎症并改善认知表现，而长期暴露于 cART 通过其对线粒体功能的影响导致认知障碍持续存在。我们在 50 名 cART 初治 HIV + 患者和 72 名年龄匹配的 HIV-健康对照者中，在 cART 治疗 12 周、1 年和 2 年后测量了基底节代谢物、功能连接、认知评分，以及神经丝轻链（NfL）和 tau 蛋白的血浆水平。cART 初治患者的谷氨酸（Glu）水平低于健康对照组，且与 NfL 血浆水平呈负相关。HIV + 患者与未感染患者之间没有其他显著的代谢物差异。治疗改善了 HIV + 患者的 Glu 水平，但 Glu、功能连接和认知表现之间没有关联。在两年的随访中，大脑代谢物和 NfL 和 Tau 的血浆水平保持稳定，这表明在这个相对年轻的 HIV + 个体队列中，没有 cART 神经毒性的迹象。
