Exploring the pharmacokinetic mechanisms that affect bictegravir exposure during pregnancy

Abstract Introduction Pregnancy is associated with physiological changes, resulting in altered pharmacokinetics, which may impact antiretroviral drug exposure. To assure health and prevent vertical transmission of HIV, it is imperative to reach adequate drug exposure. This study aims to determine the impact of pregnancy on bictegravir pharmacokinetics, examine mechanisms responsible for lower exposure, report on placental transfer, safety, and efficacy. Materials and methods This open-label pharmacokinetic study, included women living with HIV who used bictegravir, emtricitabine with tenofovir alafenamide. Plasma samples were obtained in third trimester, as well as 4–6 weeks postpartum. If feasible, cord blood and maternal plasma at delivery were obtained. Results Sixteen participants were included. Geometric mean area under the curve for total bictegravir was 48.8 mg*h/L (coefficient of variation (CV) 25.9%) in third trimester and 99.2 mg*L/h (CV 32.9%) postpartum, with a geometric mean ratio (90% CI) of 0.49 (0.44–0.55); 24 h post-dosing, median (IQR) unbound fractions were 0.15 (0.13–0.18)% and 0.11 (0.10–0.13) during pregnancy and postpartum, respectively. Median (IQR) ratio between pregnancy and postpartum was 173.7% (127.8–305.7) for glucuronidation-metabolite (M15) and 200.7% (150.0–224.9) for sulfation-metabolite (M20). Low-level viraemia was noted in several participants, but no vertical transmission occurred. Cord blood maternal plasma ratio (IQR) was 1.3 (1.0–1.4). No congenital anomalies were reported. Conclusion Although bictegravir exposure is decreased during pregnancy, mainly due to altered protein binding and increased glucuronidation and sulfation, trough levels remained above the PA-IC95. No vertical transmission occurred and no congenital anomalities were observed. Bictegravir was shown to have profound placental transfer.