The Impact of Antiretroviral Therapy on Neurocognitive Outcomes Among People Living with HIV in Low- and Middle-Income Countries (LMICs): A Systematic Review

Low and middle-income countries (LMICs) are the epicenter of the HIV epidemic. The scale-up of antiretroviral therapy (ART) has reduced mortality, but HIV-associated neurocognitive impairment (HANI) remains prevalent, which impacts functional performance, medication adherence, and quality of life. We aimed to evaluate the effect of ART on neurocognitive outcomes among people living with HIV/AIDS in LMICs and to identify determinants of these outcomes. We searched electronic databases and reference lists for studies published between 1996 and 2019. Two reviewers screened the primary studies for inclusion and performed the critical appraisal. Results were synthesized using the 'Synthesis without meta-analysis' approach through simple vote counting. We identified 31 studies conducted across four regions (Africa, Asia, South America, and Eastern Europe). Nine studies were cross-sectional, 15 were prospective, and seven were randomized controlled trials. The majority of the articles showed improved neurocognitive performance with ART use but found no association with treatment duration, regimen, central penetrating effectiveness, and conventional biomarkers. Despite the lack of appropriate norms and not accounting for practice effect in most studies, the evidence suggests ART is useful in the treatment of HIV-associated neurocognitive impairment (HANI) but limited in addressing legacy effects, and peripheral, and central viral reservoirs. Improved early ART treatment programs, viral reservoir eradication strategies, and identification of novel biomarkers will be critical in efforts to minimize HIV-associated neurocognitive impairment. PROSPERO registration: CRD42020152908.