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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182a921eb
Clinical Science

Pharmacokinetics and Safety of Tenofovir in HIV-Infected Women During Labor and Their Infants During the First Week of Life

Mirochnick, Mark MD*; Taha, Taha MD, PhD; Kreitchmann, Regis MD, PhD; Nielsen-Saines, Karin MD, MPH§; Kumwenda, Newton PhD†,‖; Joao, Esau MD; Pinto, Jorge MD, DSc#; Santos, Breno MD**; Parsons, Teresa PhD††; Kearney, Brian PharmD‡‡; Emel, Lynda PhD§§; Herron, Casey MS§§; Richardson, Paul MSc‖‖; Hudelson, Sarah E. BS‖‖; Eshleman, Susan H. MD, PhD‖‖; George, Kathleen MPH¶¶; Fowler, Mary G. MD, MPH‖‖,##; Sato, Paul MD***; Mofenson, Lynne MD†††; for the HPTN 057 Protocol Team

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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.

© 2014 by Lippincott Williams & Wilkins

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