Developmental Disorder Probability Scores at 6-18 Years Old in Relation to In-Utero/Peripartum Antiretroviral Drug Exposure among Ugandan Children

Abstract

(1) We examined the hypothesis that in utero/peripartum antiretroviral (IPA) exposure may affect the likelihood of developmental disorders-i.e., attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and functional impairment (FI). (2) Children and their primary caregivers were enrolled and followed for 12 months. The sample included 250 children perinatally HIV-infected (CPHIV), 250 children HIV-exposed and uninfected (CHEU) of women living with HIV, and 250 children HIV unexposed and uninfected (CHUU) at 6-18 years of age. CHEU's IPA exposure -type was established via medical records and categorized as no IPA, single-dose nevirapine with/without zidovudine (SdNVP ± AZT), SdNVP + AZT + Lamivudine (3TC), or combination ART (cART). Developmental disorders were assessed at months 0, 6, and 12 per caregiver response to standardized questions from the third edition of Behavioral Assessment System for Children. Multivariable repeated measures linear regression models estimated standardized mean differences (SMDs) with 95% confidence intervals (95% CI) according to the IPA exposure type relative to CHUU with adjustment for the dyad's sociodemographic and psychosocial factors. (3) Relative to the CHUU, outcomes were similar for CPHIV/CHEU with cART, SdNVP ± AZT, and no anti-retroviral drug exposure in the peripartum period. For CHEU relative to CHUU, SdNVP + AZT + 3TC exposure was associated with lower resiliency (SMD = -0.26, 95% CI: -0.49, -0.51), and elevated scores on ADHD (SMD = 0.41, 95% CI: 0.12, 0.70), ASD (SMD = 0.40, 95% CI: 0.19, 0.61), and EBD (SMD = 0.32, 95% CI: 0.08, 0.56) probability and functional impairment (SMD = 0.39, 95% CI: 0.18, 0.61) index scores. With the exception of ADHD, the adverse association between SdNVP + AZT + 3TC and outcomes were replicated for CPHIV vs. CHUU. (4) The results provided reassuring evidence that cART exposure in the peripartum period is unlikely to be adversely associated with developmental disorder probability scores in late childhood and adolescent years. However, the peripartum SdNVP + AZT + 3TC exposure associated elevation in developmental disorder probability and functional limitation at 6-18 years of life is a concern.

Keywords: ADHD; ASD; HIV-exposed uninfected; Uganda; adolescents; children; functional impairment; perinatal HIV infection; peripartum ART exposure; resiliency.