Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants.
BACKGROUND
Combination antiretroviral (cARV) regimens are recommended for pregnant women with HIV to prevent perinatal HIV transmission. Safety is a concern for infants who were HIV-exposed but uninfected, particularly for neurodevelopmental problems, such as language delays.


METHODS
We studied late language emergence (LLE) in HIV-exposed but uninfected children enrolled in a US-based prospective cohort study. LLE was defined as a caregiver-reported score ≤10th percentile in any of 4 domains of the MacArthur-Bates Communicative Development Inventory for 1-year olds and as ≥1 standard deviation below age-specific norms for the Ages and Stages Questionnaire for 2-year olds. Logistic regression models were used to evaluate associations of in utero cARV exposure with LLE, adjusting for infant, maternal and environmental characteristics.


RESULTS
1129 language assessments were conducted among 792 1- and 2-year-old children (50% male, 62% black and 37% Hispanic). Overall, 86% had in utero exposure to cARV and 83% to protease inhibitors. LLE was identified in 26% of 1-year olds and 23% of 2-year olds, with higher rates among boys. In adjusted models, LLE was not associated with maternal cARV or ARV drug classes in either age group. Among cARV-exposed 1-year olds, increased odds of LLE was observed for those exposed to atazanavir (adjusted odds ratio = 1.83, 95% confidence interval: 1.10-3.04), particularly after the first trimester (adjusted odds ratio = 3.56, P = 0.001), compared with atazanavir-unexposed infants. No associations of individual ARV drugs with LLE were observed among 2-year olds.


CONCLUSIONS
In utero cARV exposure showed little association with LLE, except for a higher risk of language delay observed in 1-year-old infants with atazanavir exposure.
From the *Speech, Language, Hearing Department, University of Kansas, Lawrence, KS; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; §Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY; ¶Northwestern University Feinberg School of Medicine, Psychiatry and Behavioral Sciences, Chicago, IL; ‖Epidemiology and Statistics Program, Division of Scientific Programs, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD; **Department of Research Pediatrics, Maternal, Child and Adolescent Program for Infectious Diseases and Virology, Keck School of Medicine of USC, Los Angeles, CA; ††Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA; and ‡‡National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Mabel L
ML
Rice
Bret
B
Zeldow
George K
GK
Siberry
Murli
M
Purswani
Kathleen
K
Malee
Howard J
HJ
Hoffman
Toni
T
Frederick
Ashley
A
Buchanan
Patricia A
PA
Sirois
Susannah M
SM
Allison
Paige L
PL
Williams
D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007805:Language Development Disorders / Q000139:chemically induced*; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies
D044966:Anti-Retroviral Agents