Nutritional Status and Cognitive Function in Children With or Exposed to HIV: Evidence From the HIV-Associated Neurocognitive Disorders in Zambia Study

Abstract

BACKGROUND: Despite advancements in antiretroviral therapy, children with HIV in sub-Saharan Africa remain vulnerable to HIV-associated neurocognitive disorder. Emerging evidence points to nutritional status as a predictor of cognitive outcomes in these patients. METHODS: In this prospective cohort study, children aged 8-17 with HIV and HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) controls were recruited from the Pediatric Center for Excellence in Lusaka, Zambia and completed quarterly follow-up visits over an average of 4 years, during which cognitive (e.g., Neuropsychological Z-score battery and the Global Deficit Score), and nutritional (e.g., number of meals per week, height percentile). Regression models, Lasso feature selection, and multivariable adaptive regression splines were used to identify nutritional predictors of cognition. Mediation analysis evaluated whether nutrition explained part of the HIV-cognition association. RESULTS: This study included 614 participants (336 HIV+, 209 HEU, 69 HUU). HIV+ children had poorer nutrition and worse cognitive outcomes than both control groups ( P < 0.001). Height and weight percentiles showed nonlinear threshold effects, whereas other measures (mid-upper arm circumference, food spending, head circumference) displayed linear associations with cognition. Lasso models identified a parsimonious nutritional index incorporating malnutrition, food security, protein intake, and growth measures (β = 0.27, 95% CI: 0.11-0.42). Mediation analysis indicated that nutritional status partially explained the association between HIV and cognition. CONCLUSION: Nutritional status was a predictor of cognitive outcomes across all groups, with especially strong implications for children living with HIV. These findings highlight nutrition as a target for interventions to mitigate neurocognitive impairment in pediatric HIV.