title: Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers.
abstract: OBJECTIVE
  We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children.
  
  
  METHODS
  We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs.
  
  
  RESULTS
  There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores.
  
  
  CONCLUSIONS
  There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.
authors.affiliation: aWayne State University School of Medicine and Children's Hospital of Michigan, Detroit, Michigan bUniversity of Miami Leonard M Miller School of Medicine, Miami, Florida cCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts dUniversity of Illinois at Chicago, Chicago, Illinois eTulane University Health Sciences Center, New Orleans, Louisiana fFrontier Science Technology and Research Foundation, Amherst, New York gNational Heart, Lung, and Blood Institute hEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland iBaylor College of Medicine and Texas Children's Hospital, Houston, Texas jBoston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Bret
authors.initials: B
authors.lastname: Zeldow
authors.forename: James D
authors.initials: JD
authors.lastname: Wilkinson
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Rich
authors.forename: Russell B
authors.initials: RB
authors.lastname: van Dyke
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Dooley
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Kaltman
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: William T
authors.initials: WT
authors.lastname: Shearer
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects*