Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057
Luiz Eduardo Osorio, Maria Ines Boechat, Mark Mirochnick, Newton Kumwenda, Regis Kreitchmann, Lynda Emel, Jorge Pinto, Esau Joao, Breno Santos, Molly Swenson, Kathleen George, Paul Sato, Lynne Mofenson, Karin Nielsen-Saines, HIV Prevention Trials Network (HPTN) 057 Protocol Team, Luiz Eduardo Osorio, Maria Ines Boechat, Mark Mirochnick, Newton Kumwenda, Regis Kreitchmann, Lynda Emel, Jorge Pinto, Esau Joao, Breno Santos, Molly Swenson, Kathleen George, Paul Sato, Lynne Mofenson, Karin Nielsen-Saines, HIV Prevention Trials Network (HPTN) 057 Protocol Team
Abstract
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: ClinicalTrials.gov NCT00120471.
Source: PubMed