Neurodevelopmental and Neurobehavioral Outcomes in Early Antiretroviral Treated Young Children with Perinatally-Acquired HIV Infection (PHIV) compared to Age-matched Perinatally HIV-Exposed Uninfected Children (PHEU)

Abstract

Introduction: Although early initiation of antiretroviral therapy (ART) in perinatally HIV infected (PHIV) infants significantly reduces morbidity and mortality, neurodevelopmental and neurobehavioral problems are still issues of concern. Objectives: This study aims primarily to compare neurodevelopmental outcomes and neurobehavioral outcomes between PHIV children who initiated ART within 12 months of life and perinatally HIV-exposed uninfected (PHEU) children. The secondary aims are to assess the outcomes by timing of ART initiation and to delineate factors and predictors associated with neurodevelopmental and neurobehavioral outcomes. Methods: This study was a prospective observational study which enrolled PHIV and PHEU children aged 12-56 months. Neurodevelopmental outcomes were assessed with the Mullen Scales of Early Learning (MSEL) and neurobehavioral outcomes were assessed with Child Behavioral Checklist (CBCL) at enrollment and at 12-month follow up visit. Global Developmental Impairment (GDI) was defined as Early Learning Composite (ELC) ≤ 70 on the MSEL. Logistic regression was used to compare prevalence of GDI. Clinical range behavioral problems was defined as T-score of internalizing, externalizing and total problems ≥ 64. Factor associated with GDI and behavioral problems were analyzed with generalized estimating equations (GEE) logistic regression model whiles predictors of changing ELC scores and behavioral scores were analyzed with GEE linear regression model. Results: From 2016 to 2017, 50 PHIV and 100 PHEU children were enrolled. Median (IQR) age at first assessment was 28 (19-41) months. Median (IQR) age of ART initiation was 2.9 (1.0 -5.1) months old. PHIV children had lower age-relevant Z scores for weight, height, and head circumference compared to the PHEU group (p <0.05). The prevalence of overall GDI was 32% (95% CI 20 - 47) in PHIV children and 18% (95% CI 11 - 27) in PHEU with OR 2.14 (95%CI 0.97 – 4.70, p = 0.06). There was significantly higher rate of GDI in PHIV children initiated ART after 3 month-old when compared to PHEU children (p = 0.01). Only factor associated with GDI was boy (adjusted odd ratio 4.65, 95%CI 1.09 to 19.85; p = 0.04). Predictors of changing ELC scores included no nursery school attendance (adjusted coefficient -2.83, 95% CI -5.05 to -0.60) and income less than 10,000 Baht/month (adjusted coefficient -3.16; 95% CI -5.89 to 0.44). The prevalence of internalizing, externalizing and total problem were not different between PHIV and PHEU children (p > 0.05). Caregiver depression and parenting style were risk factors for behavioral problems. Conclusion: Even the rate of GDI in preschool PHIV children who initiated ART within 12 months old was not different when compare to PHEU children, PHIV children who initiated ART after 3 months old tend to had higher rate of GDI. The behavioral problems were not different between groups. Psychosocial factors mainly contributed to these outcomes. Therefore, early ART initiation should be emphasized and these children should have appropriated monitoring and early stimulation to survive and thrive.