Intelligence and Language Outcomes in School-Aged Children who are HIV-Exposed, Uninfected: The Role of Sex, Perinatal Risk Factors, and Socioeconomic Status

Leila Kahnami^1,2Mary Lou Smith^1,3,4Ari Bitnun^5,6Jason Brophy^7,8John G. Sled^10,9Elka Miller^11,12Jennifer Bowes⁷Mariève Hurtubise⁷Lena Serghides^13,14*Julia Young^1,3*

• ¹Department of Psychology, The Hospital for Sick Children, Toronto, Canada
• ²Department of Psychology, York University, Toronto, Ontario, Canada
• ³Neurosciences and Mental Health Program, Research Institute, The Hospital for Sick Children, Toronto, Canada
• ⁴Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada
• ⁵Division of Infectious Diseases, The Hospital for Sick Children, Toronto, Canada
• ⁶Department of Pediatrics, University of Toronto, Toronto, Canada
• ⁷Division of Infectious Diseases, Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada
• ⁸Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
• ⁹Translational Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, Canada
• ¹⁰Translational Medicine Program, Research Institute, University of Toronto, Toronto, Ontario, Canada
• ¹¹Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Toronto, Ontario, Canada
• ¹²Department of Medical Imaging, CHEO, University of Ottawa, Ottawa, Canada
• ¹³Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
• ¹⁴Department of Immunology and Institute of Medical Sciences, Toronto, Canada

Background: Children who are HIV-exposed uninfected (CHEU) are at increased risk for neurodevelopmental impairments. Most studies report on neurodevelopmental outcomes in the first 2 years of life, with limited data available for school-aged CHEU. This interim study examined the intellectual and language outcomes in school-aged CHEU compared to children who are HIV-unexposed uninfected (CHUU). Setting: CHEU and CHUU aged 6–10 years recruited at two sites in Ontario, Canada. Methods: Intellectual and language abilities were measured using the WISC-V and CELF-5. Generalized linear models investigated associations of HEU-status with each neurodevelopmental outcome. An interaction term with sex was included to assess sex-specific effects. Gestational age, being small for gestational age (SGA), and household income were investigated as covariates. Results: 65 CHEU (35 female, median age 9.00 years) and 42 CHUU (18 female, 8.96 years) were included. HEU-status was associated with significantly lower working memory and expressive language scores. In males, HEU-status was associated with lower scores on working memory, processing speed, overall intelligence, core, and expressive language abilities. No significant differences were observed in females by HEU-status. Household income was associated with all measures of intelligence and language. Lower working memory scores persisted in male CHEU after adjusting for covariates. Conclusion: Male CHEU and those with lower household income were the most vulnerable to cognitive and language deficits. Working memory deficits in CHEU indicates a specific cognitive vulnerability due to HEU exposure status. Our findings highlight the need for early interventions, including ensuring financial security and close neuropsychological follow-up.