Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057

Pediatr Infect Dis J. 2017 Feb;36(2):184-188. doi: 10.1097/INF.0000000000001386.


Background: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants.

Methods: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life.

Results: Across all 3 cohorts, 89 infants had radiographs performed at either time point, and 85 had radiographs performed at both time points. Metaphyseal lucency was present in 1 case in Brazil and 2 in Malawi. Fifteen percent of infants from Brazil and 9% of infants from Malawi presented bone age discrepancies. No other abnormalities were identified in Brazil, whereas in Malawi, there were 7 more cases of wrist osteopenia, 2 of spine osteopenia and 3 other abnormalities.

Conclusion: Bone abnormalities were not uncommon in the overall cohort of HIV-exposed infants. Because of very limited study drug exposure at the time of birth, it is unlikely that TDF was associated with these findings. Untreated maternal HIV disease and/or maternal nutritional status could potentially be related to fetal bone development. This association should be explored in future cohort studies.

Trial registration: NCT00120471.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Bone Density / drug effects*
  • Brazil
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Malawi
  • Maternal Exposure
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Radiography
  • Spine / diagnostic imaging
  • Spine / pathology
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use
  • Wrist / diagnostic imaging
  • Wrist / pathology


  • Anti-HIV Agents
  • Tenofovir

Associated data