Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.

Setting: Nonrandomized, open-label, multi-center phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.

Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the 2nd and 3rd trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated LC-MS/MS methods. Within-participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between 2nd and 3rd trimester versus postpartum. Infant HIV testing results were obtained.

Results: Twenty-seven maternal-infant pairs enrolled. Bictegravir AUC0-24 was 46% lower in the 2nd trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43-0.69) and 52% lower in the 3rd trimester (n=24; P < 0.0001; GMR 0.48; 90% CI: 0.43-0.55), compared to postpartum. C24 concentrations were above the estimated bictegravir protein-adjusted EC95 of 0.162 µg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n=17; quartiles: 1.17, 1.63). Median T1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7, 45.9) with a Cmax of 2.06 µg/mL (quartiles: 1.37, 2.72). 88-92% of participants maintained suppression <40 copies/mL throughout pregnancy and postpartum. All available infant HIV testing results were negative. The safety profile for pregnant PWH and infants was acceptable.

Conclusions: Bictegravir exposure was lower during pregnancy compared to postpartum, yet C24 concentrations were greater than the bictegravir protein-adjusted EC95.