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Clinical Trial
. 2014 Jan 1;65(1):33-41.
doi: 10.1097/QAI.0b013e3182a921eb.

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

Mark Mirochnick  1 , 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; HPTN 057 Protocol Team
Affiliations
Clinical Trial

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

Mark Mirochnick et al. J Acquir Immune Defic Syndr. .

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.

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Conflict of interest statement

Conflicts of Interest: For the remaining authors no conflicts were declared.

Figures

Figure 1
Figure 1
a. Tenofovir concentration in amniotic fluid (open squares) and maternal delivery (crosses) plotted against time between maternal dosing and delivery. b. The ratio of amniotic fluid and maternal delivery tenofovir concentration (open triangles) plotted against time between maternal dosing and delivery.
Figure 2
Figure 2
a. Tenofovir concentration in cord blood (open diamonds) and maternal delivery (crosses) plotted against time between maternal dosing and delivery. b. The ratio of cord blood and maternal delivery tenofovir concentration (open triangles) plotted against time between maternal dosing and delivery.
Figure 3
Figure 3
Infant tenofovir concentrations (Median ± standard error) plotted against time after birth for each cohort
See this image and copyright information in PMC

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