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The objective was to determine whether maraviroc (MVC) has unique neurocognitive benefits in the context of initial antiretroviral therapy (ART).Randomized, double-blind, placebo-controlled, 48-week trial.Participants were enrolled in US AIDS Clinical Trials Group clinical trial sites.Total 262 ART-naive, chemokine coreceptor 5 tropic HIV, and HIV RNA greater than 1000 copies/ml participants were randomized, 230 participants completed the study.Participants received MVC 150 mg or tenofovir disoproxil fumarate (TDF) 300 mg on a background of ritonavir-boosted darunavir and emtricitabine.The neuropsychological battery of 15 tests done at baseline, week 24 and week 48 assessed seven domains, and were standardized into z-scores then converted into deficit scores and a global deficit score. The 48-week changes from baseline in the neuropsychological scores and the global deficit score were compared by Wilcoxon or Kruskal–Wallis test between arms, and among baseline impairment groups [classified as normal, mild (2 deficit scores ≥1) and moderate (2 deficit scores ≥2)]. It was hypothesized that the MVC arm would have improved neuropsychological performance over TDF.In this double-blind, randomized, placebo-controlled trial, there were no differences in neuropsychological performance between MVC and TDF. Those with moderate neuropsychological impairment at baseline experienced greater ART-mediated neuropsychological improvement than those with mild or no neuropsychological impairment.Improvement in neurocognitive functioning was greater with more baseline impairment but was comparable with MVC or TDF.