比克替拉韦在感染HIV的孕妇、产后妇女及其婴儿中的药代动力学和安全性

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

作者信息

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

机构信息

Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA.

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.

出版信息

J Acquir Immune Defic Syndr. 2025 Mar 1;98(3):300-307. doi: 10.1097/QAI.0000000000003571.

DOI:10.1097/QAI.0000000000003571

PMID:39813286

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11798693/

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.

摘要

背景

关于感染艾滋病毒的孕妇（PWH）中比克替拉韦的药代动力学及婴儿清除情况的数据有限。

设置

一项关于比克替拉韦在怀孕PWH及其婴儿中的药代动力学和安全性的非随机、开放标签、多中心IV期前瞻性研究。

方法

在孕中期、孕晚期及产后，对口服比克替拉韦50毫克每日一次（固定剂量复方比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺的组成部分）进行稳态24小时药代动力学采样。采集脐带血和婴儿清除样本。采用经过验证的液相色谱-串联质谱法测量总比克替拉韦和游离比克替拉韦浓度。计算参与者内部几何平均比率（GMR）及其90%置信区间（CI），以比较孕中期与孕晚期及产后的药代动力学。获取婴儿艾滋病毒检测结果。

结果

纳入了27对母婴。与产后相比，比克替拉韦在给药后0至24小时的浓度-时间曲线下面积在孕中期降低了46%（n = 12；P = 0.002；GMR 0.54；90% CI：0.43至0.69），在孕晚期降低了52%（n = 24；P < 0.0001；GMR 0.48；90% CI：0.43至0.55）。C24浓度高于比克替拉韦蛋白校正后的95%有效浓度0.162μg/mL。脐带血与母血浓度的中位数比率为1.38（n = 17；四分位数：1.17 - 1.63）。婴儿比克替拉韦清除的中位数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）。总体而言，88% - 92%的参与者在整个孕期和产后维持病毒载量低于40拷贝/mL。所有可得的婴儿艾滋病毒检测结果均为阴性。怀孕PWH及其婴儿的安全性概况是可接受的。