title: Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV-positive mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children cohort study).
abstract: OBJECTIVE
  The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children.
  
  
  BACKGROUND
  ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals.
  
  
  METHODS
  Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-).
  
  
  RESULTS
  Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference.
  
  
  CONCLUSIONS
  Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.
authors.affiliation: Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida 33101, USA. slipshultz@med.miami.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: William T
authors.initials: WT
authors.lastname: Shearer
authors.forename: Bruce
authors.initials: B
authors.lastname: Thompson
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Rich
authors.forename: Irene
authors.initials: I
authors.lastname: Cheng
authors.forename: E John
authors.initials: EJ
authors.lastname: Orav
authors.forename: Sulekha
authors.initials: S
authors.lastname: Kumar
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Pignatelli
authors.forename: Louis I
authors.initials: LI
authors.lastname: Bezold
authors.forename: Philip
authors.initials: P
authors.lastname: LaRussa
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Starc
authors.forename: Julie S
authors.initials: JS
authors.lastname: Glickstein
authors.forename: Sharon
authors.initials: S
authors.lastname: O'Brien
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Cooper
authors.forename: James D
authors.initials: JD
authors.lastname: Wilkinson
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Miller
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000276:immunology*; D006679:HIV Seropositivity / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D012307:Risk Factors; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D044966:Anti-Retroviral Agents