Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants

Abstract

Objective: Antiretroviral (ARV) drugs are routinely provided to HIV-infected pregnant women to prevent HIV mother-to-child transmission. Although ARV use has significantly reduced mother-to-child transmission to <2% in the United States, it remains crucial to monitor uninfected infants and children for adverse consequences of in utero ARV exposure.

Methods: We studied neurodevelopmental function in HIV-exposed uninfected children who were enrolled in Pediatric AIDS Clinical Trials Group 219/219C, a multisite, prospective, cohort study. Mental and motor functioning were assessed with the Bayley Scales of Infant Development (BSID), first and second editions. ARV exposure information was collected during pregnancy or within the first years of life. Linear regression methods were used to evaluate the association of in utero ARV exposure on Mental Developmental Index and Psychomotor Developmental Index at 2 years of age, controlling for demographic factors (age, gender, and race/ethnicity) and potential confounders: test version, primary language, primary caregiver, caregiver education level, low birth weight, geographic and urban/rural location, birth year, and maternal illicit drug use.

Results: Among 1840 infants who were born between 1993 and 2006, 1694 (92%) were exposed to ARV in utero and 146 (8%) were not exposed. After controlling for confounders, children who were exposed in utero to any ARV did not have lower Mental Developmental Index and Psychomotor Developmental Index scores than unexposed children. Among low birth weight infants, significantly higher BSID scores were observed for prenatally ARV-exposed than unexposed children. Maternal illicit drug use was reported for 17% of mothers but was not associated with BSID scores.

Conclusions: Mental and motor functioning scores were not lower for infants with in utero ARV exposure compared with no exposure. Although these results are reassuring, continued evaluation of uninfected children with in utero ARV exposure for long-term adverse outcomes is important.

FIGURE 1

MDI and PDI scores overall and by birth weight; estimated least squares means for 1840 HIV-exposed uninfected children in PACTG 219/219C at age 2 years, by exposure to ARV treatment (ART). Least squares means are adjusted for exact age at test, birth year, gender, race/ethnicity, type of caregiver, caregiver education level, primary language, region of country, site size, rural/urban site classification, and BSID test version.

FIGURE 2

MDI and PDI scores overall and by BSID test version (I or II); estimated least squares means for 1840 HIV-exposed uninfected children in PACTG 219/219C at age 2 years, by exposure to ARV treatment (ART). Least squares means are adjusted for exact age at test, birth year, gender, race/ethnicity, type of caregiver, caregiver education level, primary language, birth weight, region of country, site size, and rural/urban site classification.