Clinical Trials, St Mary's Hospital, Imperial College London, London, UK.
Clin Infect Dis. 2010 Mar 15;50(6):920-9. doi: 10.1086/650743.
Neurocognitive impairment remains prevalent, despite combination antiretroviral therapy (cART). Differences between changes in cerebral function and alternative cARTs have not been prospectively assessed.
Treatment-naive, HIV-1-infected individuals randomly allocated to commence cART (tenofovir-emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir [arm 2], or zidovudine-abacavir [arm 3]) were eligible. Cerebral function tests included neurocognitive testing and assessment of cerebral metabolites using proton magnetic resonance spectroscopy in several anatomical voxels, including right frontal white matter and right basal ganglia, at baseline and after 48 weeks. N-acetylaspartate-to-creatine (NAA/Cr) ratios were calculated. Both the differences between changes in neurocognitive function and NAA/Cr ratios over 48 weeks and the study arms (arm 1 vs arm 2; arm 1 vs arm 3) were assessed.
Thirty subjects completed study procedures (9, 9, and 12 subjects in arms 1, 2, and 3, respectively). Mean CD4+ cell counts (+/- standard deviation) were 218 +/- 87 cells/microL at baseline and 342 +/- 145 cells/microL at week 48. The mean plasma HIV-1 RNA level was <50 copies/mL for 28 of the 30 subjects at week 48. Over 48 weeks, greater improvements in identification reaction time (P = .04) and executive function (P = .02) were observed in arm 3, compared with arm 1 (0.03, -0.30, -0.50 log10 ms change in identification reaction time, in arms 1, 2, and 3, respectively). Increases in the NAA/Cr ratio were observed in all voxels (maximum 38% in right basal ganglia), with greater increases observed in arm 1 than in arm 2 (P = .03) in frontal white matter (30%, -7%, and 0% change in the NAA/Cr ratio, in arms 1, 2, and 3, respectively).
To our knowledge, this is the first study to prospectively describe different changes in cerebral function testing parameters between different cARTs. Greater improvements in neuronal recovery (NAA/Cr ratio) were observed for recipients of tenofovir-emtricitabine plus efavirenz (arm 1), and greater improvements in neurocognitive function testing were observed for recipients of tenofovir-emtricitabine plus zidovudine-abacavir (arm 3).
尽管采用了联合抗逆转录病毒疗法（cART），但神经认知障碍仍然普遍存在。尚未前瞻性评估大脑功能变化与替代 cART 之间的差异。
治疗初治的 HIV-1 感染者随机分配开始 cART（替诺福韦-恩曲他滨加依非韦伦[第 1 组]、阿扎那韦-利托那韦[第 2 组]或齐多夫定-阿巴卡韦[第 3 组]）。脑功能测试包括神经认知测试和使用质子磁共振波谱在多个解剖体素（包括右额白质和右基底节）中评估脑代谢物，基线和 48 周后进行。计算 N-乙酰天门冬氨酸与肌酸（NAA/Cr）比值。评估 48 周内神经认知功能变化和 NAA/Cr 比值的差异以及研究组（第 1 组与第 2 组；第 1 组与第 3 组）。
30 名受试者完成了研究程序（第 1、2 和 3 组分别有 9、9 和 12 名受试者）。平均 CD4+细胞计数（+/-标准差）为 218 +/- 87 个/微升，基线为 342 +/- 145 个/微升。第 48 周时，28 名受试者中的 30 名的血浆 HIV-1 RNA 水平<50 拷贝/mL。与第 1 组相比，第 3 组在识别反应时间（P =.04）和执行功能（P =.02）方面有更大的改善（第 1、2 和 3 组的识别反应时间分别为 0.03、-0.30 和-0.50 个 log10 毫秒）。在所有体素中均观察到 NAA/Cr 比值增加（右侧基底节最大增加 38%），与第 2 组相比，第 1 组的增加更为明显（P =.03）（NAA/Cr 比值在第 1、2 和 3 组分别为 30%、-7%和 0%的变化）。
据我们所知，这是第一项前瞻性描述不同 cART 之间大脑功能测试参数变化的研究。替诺福韦-恩曲他滨加依非韦伦（第 1 组）组观察到神经元恢复（NAA/Cr 比值）的改善更大，而替诺福韦-恩曲他滨加齐多夫定-阿巴卡韦（第 3 组）组观察到神经认知功能测试的改善更大。
