Pharmacokinetics and safety of tenofovir in hiv-infected women during labor and their infants during the first week of life

Mark Mirochnick, Taha Taha, Regis Kreitchmann, Karin Nielsen-Saines, Newton Kumwenda, Esau Joao, Jorge Pinto, Breno Santos, Teresa Parsons, Brian Kearney, Lynda Emel, Casey Herron, Paul Richardson, Sarah E. Hudelson, Susan H. Eshleman, Kathleen George, Mary G. Fowler, Paul Sato, Lynne Mofenson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume65
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Neonate
  • Pharmacokinetics
  • Tenofovir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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