Impact of HAART therapy on cognitive function in patients with HIV: a systematic review of randomized control trial

Background: Cognitive impairment remains common in adults with HIV despite effective viral suppression on combination antiretroviral therapy. We systematically reviewed randomized trials evaluating the impact of different regimens or intensification strategies on cognitive outcomes. Methods: Following PRISMA, we searched PubMed, Scopus, Cochrane Library, and Web of Science from inception to 5 September 2025 for randomized controlled trials in adults that compared cognitive outcomes between combination antiretroviral regimens, placebo or no intensification. Eligible trials reported neuropsychological or cognitive test results. Risk of bias was assessed with the Cochrane ROB 2 tool. Owing to heterogeneity of cognitive measures, data were synthesized narratively. Results: Six trials (721 participants) met the criteria. Three evaluated initial regimens in antiretroviral-naïve participants and three tested maraviroc (MVC)- or dolutegravir-based intensification in virally suppressed individuals with neurocognitive impairment. Outcomes included global composite scores and domain-specific measures of memory, attention, executive function, processing/psychomotor speed, and motor function. Within-arm improvements were generally small; only one small pilot trial reported moderate cognitive benefit with MVC intensification. Larger trials did not show significant advantages of alternative or intensified regimens over standard therapy. Safety profiles were similar between arms. Conclusion: Available randomized evidence does not demonstrate a consistent additional cognitive benefit of alternative or intensified combination antiretroviral regimens beyond standard therapy with viral suppression. Given the small number and size of trials, modest regimen-specific effects in subgroups cannot be excluded. Future studies should use larger samples, harmonized outcome measures, and evaluate multimodal interventions combining optimized antiretroviral therapy with adjunctive pharmacological and non-pharmacological approaches.