Neurocognitive Effects of Antiretroviral Initiation Among People Living With HIV in Rural Uganda

Background: HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda. Methods: Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes. Results: Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD +/- 8.5 years) and mean education of 5.4 years (SD +/- 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P= 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P< 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance. Conclusions: PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.