Background:  A5199 is an ongoing study to evaluate the prevalence and incidence of neurological disease in 860 persons with HIV-1 and the effect of ART on neurological disease in resource-limited settings.

Methods:  Participants were enrolled in Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe. Standardized neurological and neuropsychological exams (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks. The present analysis was limited to 293 participants who were randomized to treatment with didanosine enteric-coated (ddI) + emtricitabine (FTC) + atazanavir (ATV) in AIDS Clinical Trials Group (ACTG) Study A5175 (PEARLS). Changes in neurological and neuropsychological function were analyzed with linear and logistic GEE regression models.

Results:  Baseline characteristics were 54% female, 48% black, median (Q1, Q3) screening CD4 of 182 (96, 235), median (Q1, Q3) entry plasma HIV-1 RNA log₁₀ 5.0 copies/mL (2.6, 5.9). Abnormal baseline assessments included:  29% with abnormal overall neurological assessment, 23% with neuropathy, 6% with focal central nervous system (CNS) disease, 10% with diffuse CNS disease, 6% with mild neurocognitive disorder, and 1% with HIV-associated dementia (HAD). Significant improvements in neuropsychological functioning (p <0.01 for all tests) after ART initiation were observed after controlling for baseline function, age, sex, country, CD4, plasma HIV-1 RNA stratum, and years of education, although effect sizes were modest and varied by country. The odds of neuropathy (p = 0.03, OR = 0.81, 95%CI 0.67, 0.98) and focal CNS disease (p = 0.02, OR = 0.46, 95%CI 0.24, 0.88) decreased for each additional 24 weeks of follow-up after controlling for the above covariates. Significant changes in overall neurological function or diffuse CNS disease were not observed. HAD, mild neurocognitive disease, and other neurological diagnoses were uncommon.

Conclusions:  Significant improvement in neuropsychological function occurred after initiation of ART in resource-limited settings. The magnitude of improvement in neuropsychological performance varied by country. Improvements may be due to control of HIV through ART effects or practice effects, or both. Variation in neuropsychological performance across countries could reflect differences in population characteristics, test administration, HIV-1 subtypes, or ART resistance patterns. Future work will address these issues.