Pharmacokinetics of tenofovir during pregnancy and postpartum

for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response.

Original languageEnglish (US)
Pages (from-to)502-511
Number of pages10
JournalHIV Medicine
Volume16
Issue number8
DOIs
StatePublished - Sep 1 2015

Fingerprint

Tenofovir
Postpartum Period
Pharmacokinetics
Pregnancy
Area Under Curve
Third Pregnancy Trimester
Pregnant Women
Second Pregnancy Trimester
HIV
Mothers
Confidence Intervals
Weights and Measures

Keywords

  • Antiretrovirals
  • HIV
  • Pregnancy
  • Prevention of perinatal transmission
  • Tenofovir

ASJC Scopus subject areas

  • Health Policy
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team (2015). Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Medicine, 16(8), 502-511. https://doi.org/10.1111/hiv.12252

Pharmacokinetics of tenofovir during pregnancy and postpartum. / for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team.

In: HIV Medicine, Vol. 16, No. 8, 01.09.2015, p. 502-511.

Research output: Contribution to journalArticle

for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team 2015, 'Pharmacokinetics of tenofovir during pregnancy and postpartum', HIV Medicine, vol. 16, no. 8, pp. 502-511. https://doi.org/10.1111/hiv.12252
for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team. Pharmacokinetics of tenofovir during pregnancy and postpartum. HIV Medicine. 2015 Sep 1;16(8):502-511. https://doi.org/10.1111/hiv.12252
for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team. / Pharmacokinetics of tenofovir during pregnancy and postpartum. In: HIV Medicine. 2015 ; Vol. 16, No. 8. pp. 502-511.
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abstract = "Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50{\%}) in the second trimester, 27 of 37 women [73{\%}; 95{\%} confidence interval (CI) 56{\%}, 86{\%}] in the third trimester, and 27 of 32 women (84{\%}; 95{\%} CI 67{\%}, 95{\%}) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response.",
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T1 - Pharmacokinetics of tenofovir during pregnancy and postpartum

AU - for the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s Team

AU - Best, B. M.

AU - Burchett, S.

AU - Li, H.

AU - Stek, A.

AU - Hu, C.

AU - Wang, J.

AU - Hawkins, E.

AU - Byroads, M.

AU - Watts, D. H.

AU - Smith, E.

AU - Fletcher, Courtney V

AU - Capparelli, E. V.

AU - Mirochnick, M.

AU - Aweeka, Francesca

AU - Chotivanich, Nantasak

AU - Cressey, Tim Roy

AU - Frenkel, Lisa M.

AU - Gupta, Amita

AU - Jennings, Amy

AU - Jourdain, Gonzague

AU - Kreitchmann, Regis

AU - Patel, Rita

AU - Rungruengthanakit, Kittipong

AU - Shapiro, David

AU - Sukrakanchana, Pra ornsuda

AU - Kovacs, Andrea

AU - Homans, James

AU - Spencer, LaShonda

AU - Kramer, Francoise

AU - Buschur, Shelley

AU - Hammill, Hunter

AU - Paul, Mary E.

AU - McMullen-Jackson, Chivon

AU - Melvin, Ann

AU - Venema-Weiss, Corry

AU - Lane, Jenna

AU - Hitti, Jane

AU - Knapp, Katherine

AU - Edwin Thorpe, E. T.

AU - Utech, L. Jill

AU - Sublette, Nina

AU - Wara, Diane

AU - Cohan, Deborah

AU - Tilton, Nicole

AU - Vachon, Mary Elizabeth

AU - Baig, Mirza Mahboobullah

AU - Purswani, Murli Udharam

AU - Gutierrez, Jenny

AU - Luzuriaga, Katherine

AU - Cormier, Sharon

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response.

AB - Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. Methods: International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24h post dose (AUC) was ≥1.99μg h/mL (nonpregnant historical control 10th percentile). Results: The median tenofovir AUC was decreased during the second (1.9μg h/mL) and third (2.4μg h/mL; P=0.005) trimesters versus postpartum (3.0μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P>0.05). Median second/third-trimester troughs were lower (39/54ng/mL) than postpartum (61ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2kg, respectively; P=0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. Conclusions: This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (>90kg) or inadequate HIV RNA response.

KW - Antiretrovirals

KW - HIV

KW - Pregnancy

KW - Prevention of perinatal transmission

KW - Tenofovir

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DO - 10.1111/hiv.12252

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EP - 511

JO - HIV Medicine

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