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Evaluation of Risk for Late Language Emergence After In Utero Antiretroviral Drug Exposure in HIV-exposed Uninfected Infants

Rice, Mabel L. PhD*; Zeldow, Bret MS; Siberry, George K. MD, MPH; Purswani, Murli MD§; Malee, Kathleen PhD; Hoffman, Howard J. MA; Frederick, Toni PhD, MSPH**; Buchanan, Ashley MS; Sirois, Patricia A. PhD††; Allison, Susannah M. PhD‡‡; Williams, Paige L. PhDfor the Pediatric HIVAIDS Cohort Study (PHACS)

The Pediatric Infectious Disease Journal: October 2013 - Volume 32 - Issue 10 - p e406–e413
doi: 10.1097/INF.0b013e31829b80ee
HIV Reports

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.

Accepted for publication May 12, 2013.

The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or U.S. Department of Health and Human Services.

Preliminary results from this analysis were presented at the 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, Feb 27–Mar 2, 2011, Abstract #751.

The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Mabel L. Rice, PhD, 1000 Sunnyside Avenue, 3031 Dole Human Development Center, University of Kansas, Lawrence, KS 66045. E-mail:

© 2013 by Lippincott Williams & Wilkins, Inc.