From the Departments of Neurology (M.T.W., M.N.U., G.S.), Obstetrics and Gynecology (M.T.W.), and Biomedical Engineering (A.F., J.Z.), University of Rochester, NY; Department of Infectious Disease (E.A.R.), SUNY Upstate Medical Center, Syracuse, NY; Department of Internal Medicine (R.C.A.), McGovern Medical School at The University of Texas Health Science Center at Houston; Departments of Biostatistics and Computational Biology (L.W., X.Q., G.S.), Imaging Sciences (M.E.T., J.Z.), and Neuroscience (M.E.T.), University of Rochester Medical Center; and Department of Physics and Astronomy (J.Z.), University of Rochester, NY.
Neurology. 2022 Sep 6;99(10):e1045-e1055. doi: 10.1212/WNL.0000000000200829. Epub 2022 Jun 22.
While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated.
We recruited 3 groups of participants from the University of Rochester, McGovern Medical School, and SUNY Upstate Medical University: (1) ART treatment-naive PWH; (2) age-matched HCs; and (3) ECs. Participants underwent brain MRI and clinical and neuropsychological assessments at baseline, 1 year, and 2 years. PWH were also assessed 12 weeks after initiating cART. Volumetric analysis and fractal dimensionality (FD) were calculated for cortical and subcortical regions. Mixed effect regressions examined the effect of group and imaging variables on cognition.
We enrolled 47 PWH, 58 HCs, and 10 ECs. At baseline, PWH had worse cognition and lower cortical volumes than HCs. Cognition improved after initiation of cART and remained stable over time. Greater cortical thickness was associated with better cognition at baseline; greater FD of parietal, temporal, and occipital lobes was associated with better cognition at baseline and longitudinally. At baseline, ECs had worse cognition, lower cortical thickness, and lower FD in all 4 lobes and caudate than PWH and HCs. Greater cortical thickness, hippocampal volumes, and FD of frontal, temporal, and occipital lobes were associated with better cognition longitudinally.
Initiation of cART in PWH is associated with improvement in brain structure and cognition. However, significant differences persist over time when compared with HCs. Similar trends in ECs suggest that results are due to HIV infection rather than treatment. Stronger associations between cognition and FD suggest this imaging metric may be a more sensitive marker of neuronal injury than cortical thickness and volumetric measures.
虽然联合抗逆转录病毒疗法（cART）极大地提高了艾滋病毒感染者（PWH）的预期寿命，但仍有近 50%的人会出现与 HIV 相关的神经认知障碍。这可能是由于之前未得到控制的 HIV 病毒复制、由残留病毒复制或其他来源的激活引起的免疫激活，或 cART 相关的神经毒性所致。本研究旨在确定与未接受治疗的 HIV 阴性对照（HCs）和 HIV 精英控制者（ECs）相比，在开始 cART 前后，cART 对 PWH 的认知和神经影像学生物标志物的影响。
我们从罗切斯特大学、麦戈文医学院和纽约州立大学上州医科大学招募了三组参与者：（1）未接受 ART 治疗的 PWH；（2）年龄匹配的 HCs；（3）ECs。参与者在基线、1 年和 2 年时接受脑 MRI 和临床及神经心理学评估。PWH 还在开始 cART 后 12 周接受了评估。对皮质和皮质下区域进行了容积分析和分形维数（FD）的计算。混合效应回归检验了组间和影像学变量对认知的影响。
我们纳入了 47 名 PWH、58 名 HCs 和 10 名 ECs。基线时，PWH 的认知功能和皮质体积均低于 HCs。cART 启动后认知功能得到改善，并在随访期间保持稳定。基线时皮质厚度越大，认知功能越好；顶叶、颞叶和枕叶的 FD 越大，基线和随访时认知功能越好。基线时，ECs 的认知功能较 PWH 和 HCs 更差，4 个脑叶和尾状核的皮质厚度、FD 均更低。额叶、颞叶和枕叶的皮质厚度、海马体积和 FD 越大，认知功能随时间的改善越明显。
PWH 开始 cART 治疗与脑结构和认知功能的改善有关。然而，与 HCs 相比，这种差异在随访期间仍持续存在。ECs 中也出现了类似的趋势，这表明结果是由 HIV 感染引起的，而不是治疗引起的。认知与 FD 之间的关联更强，这表明与皮质厚度和容积测量相比，FD 可能是神经元损伤的更敏感标志物。
