a. Nutritional Status and Cognitive Function in Children with or exposed to HIV: Evidence from the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) Study

William Raskopf; Esau Mbewe; Heather Adams; Alexandra Buda; Gretchen Birbeck; Caroline Kabwe; Milimo Mweemba; Pelekelo Kabundula; Jeremiah Banda; David Bearden

doi:10.1097/QAI.0000000000003811

a. Nutritional Status and Cognitive Function in Children with or exposed to HIV: Evidence from the HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) Study

J Acquir Immune Defic Syndr. 2025 Dec 2. doi: 10.1097/QAI.0000000000003811. Online ahead of print.

Authors

Affiliations

¹ University of Rochester School of Medicine.
² Department of Educational Psychology, University of Zambia, Lusaka, Zambia.
³ University of Rochester/CHET.
⁴ University Teaching Hospital, Neurology Research Office, Lusaka Zambia.
⁵ Department of Psychology, University of Zambia, Lusaka, Zambia.
⁶ Department of Epidemiology and Biostatistics, University of Zambia, Lusaka, Zambia.

PMID: 41328951
DOI: 10.1097/QAI.0000000000003811

Abstract

Background: Despite advancements in antiretroviral therapy (ART), children with HIV in Sub-Saharan Africa remain vulnerable to HIV-associated neurocognitive disorder (HAND). Emerging evidence points to nutritional status as an 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 four years, during which cognitive (e.g., Neuropsychological Z-score battery (NPZ5) and the Global Deficit Score (GDS)), 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, while 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.

Keywords: HAND; HIV; Nutrition; Zambia; cognitive impairment; pediatric.