Changes in Cognitive Function Over 96 weeks in Naïve Patients Randomised to Darunavir-ritonavir plus either Raltegravir or Tenofovir-Emtricitabine: a substudy of the NEAT001/ANRS143 trial.

BACKGROUND:: Improvements in cognitive function are described after initiation of combination antiretroviral therapy (cART), with sparse data on differences between cART strategies. METHODS:: We assessed changes in cognition, over 96 weeks, in therapy naïve HIV-positive adults randomised to darunavir/ritonavir (800/100mg once daily) with either raltegravir (400mg twice daily, Arm1) or tenofovir/emtricitabine (245/200mg once daily, Arm2). Seven cognitive tests were administered at baseline and week 96. Changes from baseline in individual cognitive test scores and composite score (NPZ) were assessed. Comparisons between treatment arms were by intention-to-treat and associations with immunological and virological parameters by regression models. FINDINGS:: Of 343 subjects enrolled, 208 completed the week 96 cognitive assessment. Baseline median (IQR) CD4+ count and plasma HIV RNA was 348(282-398) cells/uL and 4.7(4.2-5.1) log10 copies/mL, respectively. At week 96, numbers with plasma HIV RNA undetectable and remaining on randomised cART were 85(92%) and 110(96%), and 84(90%) and 107(93%) in Arm1 and Arm2, respectively. Overall, performance significantly improved by week 96 in 5 of 7 individual tests and in NPZ. Mean change in NPZ was 0.28 versus 0.21 for Arm1 and 2, respectively (p=0.37). No statistically significant differences between study treatment arms were observed in individual cognitive domains apart from attention (greater improvement in Arm1, p=0.0499). At week 96, NPZ-score increase was associated with increase in CD4+ (p=0.001) but not HIV RNA area-under-curve (p=0.60). INTERPRETATION:: Subsequent to the initiation of cART, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function.