Department of Medicine, Hawaii Center for AIDS, University of Hawaii, Honolulu, HI, USA.
Neurology. 2013 May 7;80(19):1792-9. doi: 10.1212/WNL.0b013e318291903f. Epub 2013 Apr 17.
We evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs).
In this cross-sectional study, 35 HIV+ subjects aged ≥40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA <10 copies/10(6) cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV+ subjects were on combination antiretroviral therapy ≥1 year; all but 1 had plasma HIV RNA <50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV+ subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age.
Relative to the HIV+ group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (-14%, p = 0.020) and total subcortical (-10%, p = 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p < 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels.
Inability to clear peripheral blood of HIV DNA is associated with regional brain atrophy in well-controlled HIV infection, supporting the involvement of peripheral viral reservoirs in the neuropathogenesis of persistent HIV-related neurocognitive disorders.
我们评估了外周血单个核细胞（PBMC）中 HIV DNA 与脑区容积和脑代谢物水平的相关性。
在这项横断面研究中，我们纳入了 35 名年龄≥40 岁的 HIV+患者（25 名患者的 PBMC 中可检测到 HIV DNA；10 名患者的 HIV DNA<10 拷贝/10(6)细胞，即检测下限）和 12 名血清阴性对照者，他们均接受了 3T 磁共振脑结构成像和磁共振波谱检查。HIV+患者均接受了至少 1 年的联合抗逆转录病毒治疗；除 1 名患者外，其余患者的血浆 HIV RNA<50 拷贝/ml。我们采用逻辑回归分析评估了可能的预测变量与 HIV+患者 PBMC HIV DNA 可检测性之间的关系。采用协方差分析，在控制年龄的情况下，评估了 HIV 血清状态和 HIV DNA 对脑区容积（相对于颅内容积）和代谢物相对于肌酸比值的影响。
与 PBMC 中 HIV DNA 不可检测的 HIV+患者相比，可检测到 HIV DNA 的患者的小脑（-14%，p=0.020）和全皮质下灰质（-10%，p=0.024）容积减小。与健康对照者相比，仅可检测到 HIV DNA 的 HIV+患者的侧脑室显著增大（p<0.05），尾状核、壳核、丘脑、海马、伏隔核、脑干、全皮质灰质和脑白质容积减小。可检测到的 HIV DNA 与脑代谢物水平的显著改变无关。
在外周血中不能清除 HIV DNA 与 HIV 控制良好感染中的脑区萎缩有关，支持外周病毒库参与持续性 HIV 相关神经认知障碍的发病机制。
