title: Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life.
abstract: BACKGROUND
  Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking.
  
  
  METHODS
  The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk tenofovir concentrations were determined by liquid chromatographic-tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing.
  
  
  RESULTS
  One hundred twenty-two mother-infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults, and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%-97% of infants receiving daily dosing.
  
  
  CONCLUSIONS
  A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment.
authors: *Department of Pediatrics, Boston University School of Medicine, Boston, MA; †Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; ‡HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil; §Department of Pediatrics, David Geffen UCLA School of Medicine, Los Angeles, CA; ‖Malawi College of Medicine, Blantyre, Malawi; ¶Infectious Diseases Department, Hospital Federal dos Servidores do Estado, Rio de Janiero, Brazil; #Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; **Serviço de Infectologia, Hospital Nossa Senhora da Conceicao, Porto Alegre, Rio Grande do Sul, Brazil; ††Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ‡‡Gilead Sciences, Foster City, CA; §§Statistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‖‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; ¶¶Family Health International, Durham, NC; ##Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda; ***National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and †††Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD.
authors: Mark
authors: M
authors: Mirochnick
authors: Taha
authors: T
authors: Taha
authors: Regis
authors: R
authors: Kreitchmann
authors: Karin
authors: K
authors: Nielsen-Saines
authors: Newton
authors: N
authors: Kumwenda
authors: Esau
authors: E
authors: Joao
authors: Jorge
authors: J
authors: Pinto
authors: Breno
authors: B
authors: Santos
authors: Teresa
authors: T
authors: Parsons
authors: Brian
authors: B
authors: Kearney
authors: Lynda
authors: L
authors: Emel
authors: Casey
authors: C
authors: Herron
authors: Paul
authors: P
authors: Richardson
authors: Sarah E
authors: SE
authors: Hudelson
authors: Susan H
authors: SH
authors: Eshleman
authors: Kathleen
authors: K
authors: George
authors: Mary G
authors: MG
authors: Fowler
authors: Paul
authors: P
authors: Sato
authors: Lynne
authors: L
authors: Mofenson
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D007743:Labor, Obstetric / Q000187:drug effects*; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine
references: HIV Med. 2009 Aug;10(7):397-406
references: 19459986
references: Antimicrob Agents Chemother. 2006 Oct;50(10):3297-304
references: 17005808
references: AIDS. 1998 Jun 18;12(9):F79-83
references: 9662190
references: J Clin Pharmacol. 2007 Jun;47(6):751-9
references: 17519400
references: N Engl J Med. 2003 Sep 18;349(12):1157-67
references: 13679531
references: Antimicrob Agents Chemother. 2008 Sep;52(9):3144-60
references: 18573931
references: Antimicrob Agents Chemother. 2011 Dec;55(12):5914-22
references: 21896911
references: Science. 2010 Sep 3;329(5996):1168-74
references: 20643915
references: Antimicrob Agents Chemother. 2011 Jun;55(6):2961-7
references: 21464249
references: AIDS. 2008 May 11;22(8):973-81
references: 18453857
references: Clin Pharmacol Ther. 2009 Feb;85(2):182-9
references: 18987623
references: J Acquir Immune Defic Syndr. 2007 Jul 1;45(3):274-9
references: 17414929
references: Clin Pharmacokinet. 2004;43(9):595-612
references: 15217303
references: N Engl J Med. 2012 Aug 2;367(5):411-22
references: 22784040
references: N Engl J Med. 2010 Dec 30;363(27):2587-99
references: 21091279
references: N Engl J Med. 2012 Aug 2;367(5):399-410
references: 22784037
references: AIDS Res Hum Retroviruses. 1998 Jun 10;14(9):761-73
references: 9643376