title: Meconium Tenofovir Concentrations and Growth and Bone Outcomes in Prenatally Tenofovir Exposed HIV-Uninfected Children.
abstract: BACKGROUND
  Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV-infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV toxicity was demonstrated in animals, but most clinical investigations have not observed toxicity in humans.
  
  
  METHODS
  We evaluated HIV-exposed, uninfected infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF for ≥ 8 third trimester weeks. Infant dual-energy X-ray absorptiometry scans were obtained at 0-4 weeks to measure whole body bone mineral content. Meconium TFV concentrations were quantified by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Fifty-eight TFV-exposed infants had meconium TFV quantified. Detectable concentrations were 11-48,100 ng/g; 3 infants had undetectable concentrations. Maternal TDF prescription duration ranged from 8 to 41 gestational weeks; infant gestational ages were 36-41 weeks. Meconium TFV concentrations were not correlated with TFV exposure duration or timing and did not vary by concomitant prescription of protease inhibitors. Increased meconium TFV concentrations were associated with greater gestational ages (ρ = 0.29, P = 0.03) and lower maternal plasma HIV RNA before delivery (ρ = -0.29, P = 0.04). Meconium TFV concentrations were not associated with infant weight, length (n = 58) or bone mineral content (n = 49).
  
  
  CONCLUSIONS
  For the first time, we explored associations between meconium TFV concentrations and infant growth and bone measurements; we did not observe a meconium concentration-dependent relationship for these infant outcomes. These findings support other clinical research failing to show dose-response relationships for growth and bone outcomes among intrauterine TFV-exposed infants. High meconium TFV concentrations correlated with low maternal viral load, suggesting maternal TDF adherence significantly contributes to meconium TFV concentrations.
authors.affiliation: From the *Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland; †Department of Epidemiology, ‡Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; §Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; ¶Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana; and ‖Pediatrics Department, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Himes
authors.forename: Julia W
authors.initials: JW
authors.lastname: Wu
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.forename: Katherine
authors.initials: K
authors.lastname: Tassiopoulos
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Deborah
authors.initials: D
authors.lastname: Kacanek
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Rich
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Huestis
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D018811:Maternal Exposure; D008470:Meconium / Q000737:chemistry*; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir