Kristina M Brooks1, Mauricio Pinilla2, Alice M Stek3, David E Shapiro2, Emily Barr4, Irma L Febo5, Mary E Paul6, Jaime G Deville7, Kathleen George8, Kevin Knowles9, Kittipong Rungruengthanakit10, Renee Browning11, Nahida Chakhtoura12, Edmund V Capparelli13,14, Mark Mirochnick15, Brookie M Best13,14. 1. Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO. 2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA. 3. Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA. 4. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO. 5. Department of Pediatrics, School of Medicine, University of Puerto Rico, San Juan, PR. 6. Baylor College of Medicine, Texas Children's Hospital, Houston, TX. 7. David Geffen School of Medicine, University of California, Los Angeles, CA. 8. Family Health International, Durham, NC. 9. Frontier Science Foundation, Amherst, NY. 10. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 11. National Institute of Allergy and Infectious Diseases, Bethesda, MD. 12. Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD. 13. Division of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA. 14. Pediatrics Department, University of California San Diego-Rady Children's Hospital San Diego, San Diego, CA; and. 15. Boston University School of Medicine, Boston, MA.
Abstract
BACKGROUND: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. METHODS: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. RESULTS: Twenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF. CONCLUSION: TAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.
BACKGROUND: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. METHODS: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. RESULTS: Twenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF. CONCLUSION: TAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.
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