Division of Infectious Diseases, Department of Medicine.
Imperial Clinical Trials Unit, School of Public Health, Imperial College London.
AIDS. 2018 May 15;32(8):1007-1015. doi: 10.1097/QAD.0000000000001786.
Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits.
Therapy-naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1 : 1 basis to standard ART (Arm1: tenofovir-emtricitabine and atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine and darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in cognitive function across treatment arms with factors associated with cognitive function changes also assessed.
Of 60 individuals randomized (30 Arm1 and 30 Arm2), 58 were men and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4 cell count 428 (209) and 414 (229) cells/μl, Arms1 and 2, respectively. At week 48, plasma HIV RNA was less than 50 copies/ml in 55 of 56 of those completing study procedures. Cognitive function improved over 48 weeks [mean change z-score (SD) 0.16 (0.09) Arm1 and 0.25 (0.08) Arm2, P = 0.96 for differences between study arms]. A greater increase in frontal grey matter N-acetyl aspartate/creatine ratio was observed in Arm1 [ratio change of 0.071 (SD 0.16)] versus Arm2 [change -0.097 (SD 0.18), P = 0.009], although this was not associated with changes in cognitive function (P = 0.17).
Maraviroc-intensified ART had no demonstrable benefit on cognitive function in individuals initiating ART. Greater improvement in neuronal metabolites (N-acetyl aspartate/creatine) was observed with standard ART. Future work should focus on maraviroc-intensified ART in individuals with cognitive impairment.
马拉维若强化抗逆转录病毒治疗(ART)可能与认知益处相关。
未经治疗、认知无症状、HIV 阳性的个体被随机分配至标准 ART(Arm1:替诺福韦-恩曲他滨和阿扎那韦/利托那韦)或马拉维若强化 ART(Arm2:阿巴卡韦-拉米夫定和达芦那韦/利托那韦/马拉维若)组。在 48 周期间,对认知功能测试进行了详细评估,并使用质子磁共振波谱测量了脑代谢物。我们的主要终点是治疗臂之间认知功能变化的平均变化,同时评估与认知功能变化相关的因素。
60 名随机分配的个体(Arm1 组 30 名,Arm2 组 30 名)中,58 名男性,44 名白人。治疗组具有相似的疾病特征,包括总体平均(SD)基线 CD4 细胞计数分别为 428(209)和 414(229)细胞/μl,分别在 Arms1 和 2。在第 48 周,完成研究程序的 56 名个体中,有 55 名血浆 HIV RNA 小于 50 拷贝/ml。认知功能在 48 周内得到改善[Arm1 的平均变化 z 分数(SD)为 0.16(0.09),Arm2 为 0.25(0.08),P=0.96 比较研究臂之间的差异]。在 Arm1 中观察到额叶灰质 N-乙酰天冬氨酸/肌酸比的增加更大[比值变化 0.071(SD 0.16)],而在 Arm2 中比值变化为-0.097(SD 0.18),P=0.009],尽管这与认知功能的变化无关(P=0.17)。
在开始接受 ART 的个体中,马拉维若强化 ART 对认知功能没有明显益处。在标准 ART 中观察到神经元代谢物(N-乙酰天冬氨酸/肌酸)的改善更大。未来的工作应集中在认知障碍个体的马拉维若强化 ART 上。