title: Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: From the *Department of Pediatrics, David Geffen UCLA School of Medicine, Los Angeles, California; †Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts; ‡Department of Medicine, Malawi College of Medicine, Blantyre, Malawi; §Department of Obstetrics and Gynecology, Santa Casa de Misericordia, Porto Alegre, Brazil; ¶SCHARP Fred Hutchinson Cancer Research Center, Seattle, Washington; ‖Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; **Department of Infectious Diseases, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil; ††Department of Infectious Diseases, Hospital Conceicao, Porto Alegre, Brazil; ‡‡Family Health International, Durham, North Carolina; §§National Institute of Allergy and Infectious Diseases, and ¶¶Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors: Luiz Eduardo
authors: LE
authors: Osorio
authors: Maria Ines
authors: MI
authors: Boechat
authors: Mark
authors: M
authors: Mirochnick
authors: Newton
authors: N
authors: Kumwenda
authors: Regis
authors: R
authors: Kreitchmann
authors: Lynda
authors: L
authors: Emel
authors: Jorge
authors: J
authors: Pinto
authors: Esau
authors: E
authors: Joao
authors: Breno
authors: B
authors: Santos
authors: Molly
authors: M
authors: Swenson
authors: Kathleen
authors: K
authors: George
authors: Paul
authors: P
authors: Sato
authors: Lynne
authors: L
authors: Mofenson
authors: Karin
authors: K
authors: Nielsen-Saines
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001938:Brazil; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008295:Malawi; D018811:Maternal Exposure; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D014953:Wrist / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir