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Safety of Perinatal Exposure to Antiretroviral Medications: Developmental Outcomes in Infants

Sirois, Patricia A. PhD*; Huo, Yanling MS; Williams, Paige L. PhD; Malee, Kathleen PhD; Garvie, Patricia A. PhD§; Kammerer, Betsy PhD; Rich, Kenneth MD; Van Dyke, Russell B. MD*; Nozyce, Molly L. PhD**for the Pediatric HIVAIDS Cohort Study

The Pediatric Infectious Disease Journal: June 2013 - Volume 32 - Issue 6 - p 648–655
doi: 10.1097/INF.0b013e318284129a
HIV Reports

Background: This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants.

Methods: HIV-exposed, uninfected infants (age 9–15 months) enrolled in Surveillance Monitoring for Antiretroviral Therapy Toxicities, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class) and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates.

Results: As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black and 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (9% of protease inhibitor–containing regimens also included non-nucleoside reverse transcriptase inhibitors), 5% to regimens containing non-nucleoside reverse transcriptase inhibitors (without protease inhibitor) and 14% to regimens containing only nucleoside reverse transcriptase inhibitors. Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (P = 0.01).

Conclusions: These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study.

Supplemental Digital Content is available in the text.

From the *Tulane University School of Medicine, New Orleans, LA; Harvard School of Public Health, Boston, MA; Northwestern University Feinberg School of Medicine, Chicago, IL; §Consulting Psychologist; Children’s Hospital Boston, Boston, MA; University of Illinois, Chicago, IL; and **Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY.

Accepted for publication December 19, 2012.

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.

Data from this analysis were presented at the 23rd Annual Meeting of the Association for Psychological Science, Washington, DC, May 2011.

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 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 and the National Institute on Alcohol Abuse and Alcoholism through cooperative agreements with the Harvard University School of Public Health (HD052102) (Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Coprincipal Investigator: Kenneth Rich; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (Principal Investigator: Suzanne Siminski). Regulatory services and logistical support were provided by Westat, Inc (Principal Investigator: Julie Davidson). The authors have no other funding or conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Patricia A. Sirois, PhD, Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue (TW-41), New Orleans, LA 70112. E-mail:

© 2013 Lippincott Williams & Wilkins, Inc.