TY - JOUR
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, C. 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, La Shonda
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
N1 - Publisher Copyright:
© 2015 British HIV Association.
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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U2 - 10.1111/hiv.12252
DO - 10.1111/hiv.12252
M3 - Article
C2 - 25959631
AN - SCOPUS:84938744228
SN - 1464-2662
VL - 16
SP - 502
EP - 511
JO - HIV Medicine
JF - HIV Medicine
IS - 8
ER -