Pharmacokinetics of Tenofovir Alafenamide With Boosted Protease Inhibitors in Pregnant and Postpartum Women Living With HIV: Results From IMPAACT P1026s

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 pharmacoki-netic, 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 AUC tau 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 AUC tau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.

Remdesivir Use in the Real-World Setting: An Overview of Available Evidence

“…They have been historically excluded from drug development research protocols in fear of adverse pregnancy and maternal health outcomes [ 83 ]. RWE from the US showed that RDV was a potent and low-risk treatment option, promoting clinical improvement, lowering ICU and death rates, and resulting in a low incidence of serious adverse effects [ 71 , 72 , 73 , 74 ].…”

Pharmacokinetic Evaluation in Pregnancy—Current Status and Future Considerations: Workshop Summary

“…6,41 For medications given as a single dose or short term, the parallel (multiarm) design may incorporate arms for pregnant and nonpregnant or different arms based on different trimesters and postpartum. 42,43 • Comparator/Control group: The comparator used in PK in pregnancy studies is either the same individual postpartum in a longitudinal design or nonpregnant subjects. 6,41 Physiologic changes return to baseline at various rates in the postpartum period with the return ranging from several weeks to months.…”

“…6,44 For medications given as a single dose or short term, nonpregnant individuals have been used as controls in a parallel arm or PK compared to historical PK data, but differences in study design and populations can impact the assessment. 42,43 There have also been studies conducted in which pregnant individuals served as their own control for use of short-term medications. 45,46 • Sample size: The sample size is estimated to ensure that the number of participants is adequate to characterize the PK with adequate power and precision considering the study objective, design, and PK variability.…”

“…This design allows for the pregnant individual to provide PK samples during different stages of pregnancy and postpartum 6,41 . For medications given as a single dose or short term, the parallel (multiarm) design may incorporate arms for pregnant and nonpregnant participants or different arms based on different trimesters and postpartum 42,43 Comparator/Control group : The comparator used in PK in pregnancy studies is either the same individual postpartum in a longitudinal design or nonpregnant subjects 6,41 .…”

“…The timeline for postpartum sampling for a control group of 12 weeks after delivery has been considered adequate; however, the return to baseline may differ for each drug, and there are still limited data to define the postpartum period 6,44 . For medications given as a single dose or short term, nonpregnant individuals have been used as controls in a parallel arm or PK compared to historical PK data, but differences in study design and populations can impact the assessment 42,43 . There have also been studies conducted in which pregnant individuals served as their own control for use of short‐term medications 45,46 …”