Meconium tenofovir concentrations and growth and bone outcomes in prenatally tenofovir exposed HIV-uninfected children

Sarah K. Himes, Julia W. Wu, Denise L. Jacobson, Katherine Tassiopoulos, Rohan Hazra, Deborah Kacanek, Russell B. Van Dyke, Kenneth C. Rich, George K. Siberry, Marilyn A. Huestis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)851-857
Number of pages7
JournalPediatric Infectious Disease Journal
Volume34
Issue number8
DOIs
StatePublished - Aug 21 2015

Keywords

  • DXA
  • HIV-exposed uninfected children
  • antiretroviral
  • birth
  • bone
  • growth
  • meconium
  • tenofovir

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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