Long-term risk of hospitalization and chronic disease among children who were HIV-exposed uninfected (cHEU) compared to population controls in Montreal, Canada


BACKGROUND: While studies have demonstrated increased risk of morbidity and mortality among cHEU in early life, the need for specialized follow-up of cHEU once their HIV status has been confirmed negative is not clear. The primary objective of this study was to determine the long-term risk of hospitalization, and incidence of chronic disease, among cHEU compared to HIV-unexposed uninfected (cHUU) controls.
METHODS: Longitudinal cohort study linking data from the Centre Maternel et Infantile sur le SIDA (CMIS) cohort to administrative data from the Régie de l'Assurance Maladie du Quebec (RAMQ), a universal health system with unique single patient identifiers, covering all care services provided. ICD-9 codes were extracted and grouped by system for measures of chronic diseases and cHEU matched 1:3 by age, gender and postal code to cHUU controls. Survival analysis was used to determine risk of hospitalization and chronic disease.
RESULTS: Among 847 cHEU enrolled in the CMIS cohort between 1988 and 2015, 726 were linked to the RAMQ database, and matched to 2178 cHUU. Median follow-up was 11.1 [6.6 ' 15.9] years. There was a significantly higher risk of hospitalization among cHEU vs. cHUU over their life-span (HR 1.42 [1.26 ' 1.61], p<0.001), which remained significant after adjusting for gestational age (aHR 1.23 [1.08 ' 1.40], p=0.001), and in a sensitivity analysis excluding prolonged (>5 days) birth hospitalization (HR 1.21 [1.06 ' 1.41] (Figure 1). Over their lifespan, cHEU had a significantly higher risk of neuropsychiatric disorders (33.3% vs. 26.1%, RR 1.28 [1.13 ' 1.45], p<0.001) and congenital anomalies (5.5%vs. 3.5%, RR 1.58 [1.09 ' 2.3], p=0.016), though there was no difference in risk of chronic cardiovascular, respiratory or neoplastic disease.

CONCLUSIONS: In this resource-rich setting with universal health-care, cHEU had increased risk of hospitalization and neuro-psychiatric disorders, suggesting that cHEU would benefit from enhanced pediatric care, including early neurodevelopmental assessment.