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Safety of In Utero and Neonatal Antiretroviral Exposure: Cognitive and Academic Outcomes in HIV-exposed, Uninfected Children 5–13 Years of Age

Nozyce, Molly L. PhD*; Huo, Yanling MS; Williams, Paige L. PhD; Kapetanovic, Suad MD; Hazra, Rohan MD§; Nichols, Sharon PhD; Hunter, Scott PhD; Smith, Renee PhD**; Seage, George R. III ScD, MPH; Sirois, Patricia A. PhD**; for the Pediatric HIVAIDS Cohort Study

Pediatric Infectious Disease Journal: November 2014 - Volume 33 - Issue 11 - p 1128–1133
doi: 10.1097/INF.0000000000000410
HIV Reports

Background: Long-term effects of in utero and neonatal antiretroviral (ARV) exposure on cognitive and academic development in HIV-exposed, uninfected school-age children are unknown.

Methods: HIV-exposed, uninfected children, ages 5–13 years, in Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for Antiretroviral Treatment Toxicities, a US-based multisite cohort study, completed age-appropriate Wechsler intelligence and academic scales (WPPSI-III, WASI, WIAT-II-A). Associations between cognitive and academic outcomes and in utero ARV exposure by regimen, class and individual ARVs were evaluated, adjusting for potential confounders.

Results: Children completing WPPSI-IIIs (n = 350) were 49% male, 74% Black, 25% Hispanic; WASI (n = 337) and WIAT-II-A (n = 415) cohorts were similar. The percentage exposed to combination ARV (cARV) was 84% (WPPSI-III), 64% (WASI) and 67% (WIAT-II-A). Among ARV-exposed children, there were no significant associations between any ARV regimen or class and any cognitive or academic outcome. In addition, in both unadjusted models and after adjustment for caregiver IQ, sociodemographic factors and maternal health and substance use during pregnancy, no individual ARV drug was associated with significantly lower cognitive or academic scores. Factors typically associated with lower cognitive and academic scores in the general population, such as prematurity, small for gestational age, maternal alcohol use and lower maternal cognitive status, were also associated with lower scores in this study.

Conclusions: Overall, the safety of prenatal and neonatal ARV use was supported.

From the *Jacobi Medical Center, Albert Einstein College of Medicine, New York, NY; Harvard School of Public Health, Boston, MA; National Institute of Mental Health, Bethesda; §Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD; University of California, San Diego, CA; University of Chicago; **University of Illinois, Chicago, IL; ††Tulane University School of Medicine, New Orleans, LA.

Accepted for publication April 29, 2014.

Data from this analysis were presented at the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, GA, March 2013.

The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding 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; Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1; Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Kenneth Rich; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). 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 US Department of Health and Human Services.

The authors have no other funding or conflicts of interest to disclose.

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Address for correspondence: Molly L. Nozyce, PhD, Jacobi Medical Center, Albert Einstein College of Medicine, Building 1-8W16, 1400 Pelham Parkway South, Bronx, NY 10461. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.