title: Atazanavir exposure in utero and neurodevelopment in infants: a comparative safety study.
abstract: To evaluate the safety of in-utero exposure to atazanavir and neurodevelopment in perinatally HIV-exposed but uninfected (PHEU) infants.
  
  
  
  Prospective cohort study of mother-PHEU infant pairs in the Surveillance Monitoring for ART Toxicities protocol of the Pediatric HIV/AIDS Cohort Study.
  
  
  
  Pregnant women living with HIV who initiated an antiretroviral regimen during pregnancy were followed from the date of antiretroviral initiation. Women were classified according to whether the antiretroviral regimen contained atazanavir and the trimester of antiretroviral initiation. Neurodevelopment at 9-15 months was evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). We estimated mean differences for the five Bayley-III domains for atazanavir-containing regimens versus all other regimens. Models included baseline covariates and adjustment for failure to complete the Bayley-III using inverse probability weighting.
  
  
  
  PHEU infants were exposed in utero to atazanavir-containing (n = 167) and nonatazanavir-containing (n = 750) antiretroviral regimens. The adjusted mean differences (95% confidence interval) in Bayley-III domain scores for initiating an atazanavir-containing regimen in the first trimester were: cognitive, -1.5 (-6.2, 3.2); language, -3.3 (-7.6, 1.0); motor, -2.9 (-7.7, 1.9); social-emotional, 0.1 (-6.2, 6.4); and adaptive behavior, -0.1 (-4.3, 4.0). The mean differences for the second or third trimester were: cognitive, 0.4 (-3.2, 4.0); language, -3.4 (-6.2, -0.5); motor, 0.3 (-2.9, 3.4); social-emotional, -5.9 (-9.4, -2.3); and adaptive behavior, -2.5 (-5.9, 0.8).
  
  
  
  In-utero exposure to atazanavir-containing regimens compared with non-atazanavir-containing regimens may adversely affect language and social-emotional development in PHEU infants during the first year of life, but the absolute difference is small.
authors: aHarvard T.H. Chan School of Public Health, Boston, Massachusetts bDepartment of Psychiatry and Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, California cNational Institutes of Health, National Institute of Mental Health, Bethesda, Maryland dUniversity of Illinois at Chicago College of Medicine, Chicago, Illinois eTulane University School of Medicine, New Orleans, Louisiana fHarvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts, USA.
authors: Ellen C
authors: EC
authors: Caniglia
authors: Kunjal
authors: K
authors: Patel
authors: Yanling
authors: Y
authors: Huo
authors: Paige L
authors: PL
authors: Williams
authors: Suad
authors: S
authors: Kapetanovic
authors: Kenneth C
authors: KC
authors: Rich
authors: Patricia A
authors: PA
authors: Sirois
authors: Denise L
authors: DL
authors: Jacobson
authors: Sonia
authors: S
authors: Hernandez-Diaz
authors: Miguel A
authors: MA
authors: Hernán
authors: George R
authors: GR
authors: Seage
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D000069446:Atazanavir Sulfate