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

IF 2.2 3区医学 Q3 IMMUNOLOGY JAIDS Journal of Acquired Immune Deficiency Syndromes Pub Date : 2025-03-01 DOI:10.1097/QAI.0000000000003571

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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Abstract

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: 1.17-1.63). Median T 1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7-45.9) with a C max of 2.06 μg/mL (quartiles: 1.37-2.72). Overall, 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 with postpartum, yet C 24 concentrations were greater than the bictegravir protein-adjusted 95% effective concentration.

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比替格拉韦在孕妇和产后HIV感染者及其婴儿中的药代动力学和安全性。

背景：比替韦在HIV感染者（PWH）和婴儿洗脱期妊娠期的药代动力学数据有限。背景：非随机、开放标签、多中心的比替格拉韦在妊娠PWH及其婴儿中的药代动力学和安全性的iv期前瞻性研究。方法：在妊娠第2、3月及产后口服比替格拉韦（比替格拉韦/恩曲他滨/替诺福韦alafenamide固定剂量组合的组成部分）50 mg，每日1次，进行24小时稳态药代动力学采样。采集脐带血和婴儿冲洗样本。采用经验证的LC-MS/MS方法测定比替替韦总浓度和游离浓度。计算具有90%置信区间（CI）的参与者内几何平均比率（GMR），以比较妊娠第2和第3个月与产后的药代动力学。获得婴儿艾滋病毒检测结果。结果：纳入27对母婴。比替格拉韦AUC0-24在妊娠中期降低46% (n = 12；P = 0.002；GMR 0.54;90% CI: 0.43-0.69)，妊娠晚期降低52% (n=24；P < 0.0001；GMR 0.48;90% CI: 0.43-0.55)。C24浓度高于比替格拉韦蛋白调整EC95的估计值0.162µg/mL。脐带血药浓度与母体血药浓度之比中位数为1.38 (n=17；四分位数：1.17,1.63)。婴儿比替替韦洗脱期的中位T1/2为33.2小时（四分位数：25.7,45.9），Cmax为2.06µg/mL（四分位数：1.37,2.72）。结论：与产后相比，妊娠期间比替格拉韦暴露较低，但C24浓度高于比替格拉韦蛋白调节的EC95。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JAIDS Journal of Acquired Immune Deficiency Syndromes 医学-传染病学

CiteScore

5.80

自引率

5.60%

发文量

490

审稿时长

3-6 weeks

期刊介绍： JAIDS: Journal of Acquired Immune Deficiency Syndromes seeks to end the HIV epidemic by presenting important new science across all disciplines that advance our understanding of the biology, treatment and prevention of HIV infection worldwide. JAIDS: Journal of Acquired Immune Deficiency Syndromes is the trusted, interdisciplinary resource for HIV- and AIDS-related information with a strong focus on basic and translational science, clinical science, and epidemiology and prevention. Co-edited by the foremost leaders in clinical virology, molecular biology, and epidemiology, JAIDS publishes vital information on the advances in diagnosis and treatment of HIV infections, as well as the latest research in the development of therapeutics and vaccine approaches. This ground-breaking journal brings together rigorously peer-reviewed articles, reviews of current research, results of clinical trials, and epidemiologic reports from around the world.