November 2024
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18 Reads
JAIDS Journal of Acquired Immune Deficiency Syndromes
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 2 nd and 3 rd 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 2 nd and 3 rd trimester versus postpartum. Infant HIV testing results were obtained. Results Twenty-seven maternal-infant pairs enrolled. Bictegravir AUC 0-24 was 46% lower in the 2 nd trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43-0.69) and 52% lower in the 3 rd trimester (n=24; P < 0.0001; GMR 0.48; 90% CI: 0.43-0.55), compared to postpartum. C 24 concentrations were above the estimated bictegravir protein-adjusted EC 95 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 T 1/2 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 C 24 concentrations were greater than the bictegravir protein-adjusted EC 95 .