Harezlak J, Cohen R, Gongvatana A, Taylor M, Buchthal S, Schifitto G, Zhong J, Daar E S, Alger J R, Brown M, Singer E J, Campbell T B, McMahon D, So Y T, Yiannoutsos C T, Navia B A
Indiana University Fairbanks School of Public Health, 410 W 10th St., Suite 3000, Indianapolis, IN, 46202, USA,
J Neurovirol. 2014 Jun;20(3):294-303. doi: 10.1007/s13365-014-0246-6. Epub 2014 Apr 3.
The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.
接受稳定联合抗逆转录病毒疗法(CART)的慢性HIV感染者持续存在脑功能障碍的原因仍不清楚。在260名接受磁共振波谱(MRS)检查的HIV感染者中,对宿主和病毒因素及其相互作用进行了研究。在基底神经节、额叶白质和灰质中测量代谢物浓度(NAA/Cr、Cho/Cr、MI/Cr和Glx/Cr),并使用自举增强的赤池信息准则(AIC)选择最佳预测模型。根据代谢物和脑区的不同,年龄、种族、HIV RNA浓度、ADC分期、HIV感染持续时间、最低点CD4和/或它们之间的相互作用可预测代谢物浓度,特别是基底神经节NAA/Cr以及额中回NAA/Cr和Glx/Cr,而当前CD4和CPE指数很少或不能预测这些变化。这些结果首次表明,与当前和既往HIV状态相关的宿主和病毒因素导致脑代谢物持续异常,并为进一步理解慢性稳定疾病背景下的神经损伤提供了一个框架。