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Background: Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), has enhanced stability in plasma and improved safety compared to tenofovir disoproxil fumarate (TDF). TAF is administered as part of a fixed-dose combination either with or without the pharmacokinetic (PK) booster cobicistat (COBI). As COBI inhibits transporters involved in the disposition of TAF, co-administration of TAF with COBI results in higher TAF exposure. The PK of TAF have not been studied in pregnant women. This study described TAF exposure when administered with and without COBI during pregnancy and postpartum.
Methods: IMPAACT P1026s is an ongoing, nonrandomized, open-label, multi-center study of antiretroviral PK in HIV-infected pregnant women. Steady-state PK profiles of TAF following once-daily dosing of either TAF/FTC/RPV (25/200/25 mg, Odefsey┬«) or TAF/FTC/EVG/COBI (10/200/150/150 mg, Genvoya┬«) were obtained during the 2nd and 3rd trimesters (2T/3T) and 6-12 weeks postpartum (PP). TAF plasma concentrations were measured by a validated LC-MS/MS method. A two-tailed Wilcoxon signed rank test (α=0.10) was employed for paired within-subject comparison of PK parameters.
Results: A total of 42 subjects from the US were enrolled with a median age at delivery of 30.4 years (range 19.1-38.8). For the TAF 25 mg arm, TAF exposure was lower and oral clearance was higher in 3T compared to PP (Table 1). For the TAF/COBI arm, no differences were seen between any ante-partum and post-partum PK parameters. HIV RNA at delivery was < 50 copies/mL for 10/11 women in the TAF 25 mg arm and 24/27 women in the TAF/COBI arm. Median infant gestational age and weight at birth were 38.9 weeks and 3.24kg, respectively. Congenital anomalies considered possibly related to study drugs included a ventral septal defect in one infant and congenital pseudoarthrosis of the left clavicle and neonatal compartment syndrome in another infant. Overall 27/41 infants were HIV-negative and 14 were indeterminate/pending.
Conclusions: In women taking TAF without COBI, TAF exposure was lower in 3T compared to PP, whereas no differences were seen between pregnancy and PP in women taking TAF with COBI. Before TAF can be recommended for use in pregnancy additional safety and outcome data as well as intracellular PK data are needed.


Tenofovir Alafenamide Pharmacokinetic Parameters, Median (IQR)
[Tenofovir Alafenamide Pharmacokinetic Parameters, Median (IQR)]