Cognitive trajectories after treatment in acute HIV infection

Abstract

Objective: People with HIV continue to exhibit cognitive symptoms after suppressive antiretroviral therapy (ART). It remains unclear if initiating ART during acute HIV-1 infection (AHI) uniformly improves cognitive outcomes. Methods: Sixty-seven individuals (96% male, median age 28 years) initiated ART immediately after AHI diagnosis and maintained viral suppression for six years. They underwent a four-test neuropsychological battery that measured fine motor speed and dexterity, psychomotor speed, and executive functioning at baseline (pre-ART AHI), weeks 12, 24, and 96, and annually thereafter through week 288. Performances were standardized to calculate an overall (NPZ-4) score and frequencies of impaired cognitive performance (≤-1 SD on ≥2 tests, or ≤-2 SD on ≥1 test). Group-based trajectory analysis (GBTA) was applied to identify distinct neuropsychological trajectories modeled from baseline to week 288. Post-hoc analyses examined HIV-1 and demographic factors that differed between trajectory subgroups. Results: NPZ-4 scores improved from baseline to week 96 (p < 0.001) and from weeks 96 to 288 (p < 0.001), with frequencies of impaired performance of 30%, 6% and 2% at the respective time-points. The amplitude of NPZ-4 improvement throughout the period was >0.5 SD and beyond practice effects. GBTA identified three NPZ-4 trajectory subgroups that all showed improvement over-time. The subgroup with lowest baseline performance exhibited worse depressive symptoms at baseline (p = 0.04) and the largest improvement among the three. HIV-1 indices did not differ between the subgroups. Conclusions: Cognitive performance improved in a sustained and stable manner after initiating ART during AHI. Largest improvements were seen in participants with worst baseline cognitive performance.