Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants

作者：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, Xiao‐Ying Huang, Brookie M. Best, Mark Mirochnick, Jeremiah D. Momper, the IMPAACT 2026 Protocol Team · 发表于：JAIDS Journal of Acquired Immune Deficiency Syndromes · 年份：2024 · DOI：10.1097/qai.0000000000003571 · 被引用次数：7 · 研究领域：HIV/AIDS drug development and treatment、HIV-related health complications and treatments、HIV/AIDS Research and Interventions

BACKGROUND: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout. SETTING: Nonrandomized, open-label, multicenter 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 second and third trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated liquid chromatography with tandem mass spectrometry methods. Within-participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between second and third trimester versus postpartum. Infant HIV testing results were obtained. RESULTS: Twenty-seven maternal-infant pairs were enrolled. Bictegravir area under the concentration-time curve from time 0 through 24 hours post-dose was 46% lower in the second trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43 to 0.69) and 52% lower in the third trimester (n = 24; P < 0.0001; GMR 0.48; 90% CI: 0.43 to 0.55), compared with postpartum. C 24 concentrations were above the estimated bictegravir protein-adjusted 95% effective concentration of 0.162 μg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n = 17; quartiles: 1.17-1...