DOI: 10.1097/qai.0000000000003571 ISSN: 1525-4135

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

Kathleen M. Powis, Mauricio Pinilla, Flynn McMorrow, Alice Stek, Kristina M. Brooks, David E. Shapiro, Kevin Knowles, Ahizechukwu C. Eke, Elizabeth Greene, Allison Agwu, Lourdes Topete, Renee Browning, Nahida Chakhtoura, Priyanka Arora, Xiaoying Huang, Brookie M. Best, Mark Mirochnick, Jeremiah D. Momper,
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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.

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