Changes in cerebral function parameters with maraviroc intensified antiretroviral therapy in treatment naïve HIV-Positive individuals; A randomised controlled study

BACKGROUND Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS Therapy naive, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1:1 basis to standard ART (Arm1; tenofovir-emtricitabine plus atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine plus darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function (CF) tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy. Our primary endpoint was mean change in CF across treatment arms with factors associated with CF changes also assessed. RESULTS Of 60 subjects randomised (30 Arm1 and 30 Arm2), 58 were male and 44 of white ethnicity. Treatment groups had similar disease characteristics including overall mean (SD) baseline CD4+ count 428 (209) and 414 (229) cells/μL Arms1 and 2, respectively. At week 48, plasma HIV RNA was <50 copies/mL in 55/56 of those completing study procedures. CF 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 (NAA/Cr) 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 CF (P = 0.17). CONCLUSIONS Maraviroc-intensified ART had no demonstrable benefit on CF in subjects initiating ART. Greater improvement in neuronal metabolites (NAA/Cr) was observed with standard ART. Future work should focus on maraviroc-intensified ART in subjects with cognitive impairment.