Meconium Atazanavir Concentrations and Early Language Outcomes in HIV-Exposed, Uninfected Infants with Prenatal Atazanavir Exposure

Abstract

OBJECTIVE: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in one-year-olds. METHODS: Pregnant women with HIV and their uninfected infants enrolled in the SMARTT study. Meconium antiretroviral concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III). Late language emergence (LLE) was defined as ≥ one of four CDI scores ≤10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders. RESULTS: Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n=93) and CDI (n=106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower LLE risk (P=0.04), and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P=0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively). CONCLUSIONS: Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HEU infants is required.