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
{"title":"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。","authors":"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","doi":"10.1097/QAI.0000000000003571","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.</p><p><strong>Setting: </strong>Nonrandomized, open-label, multicenter phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Bictegravir exposure was lower during pregnancy compared with postpartum, yet C 24 concentrations were greater than the bictegravir protein-adjusted 95% effective concentration.</p>","PeriodicalId":14588,"journal":{"name":"JAIDS Journal of Acquired Immune Deficiency Syndromes","volume":" ","pages":"300-307"},"PeriodicalIF":2.9000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798693/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants.\",\"authors\":\"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\",\"doi\":\"10.1097/QAI.0000000000003571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout.</p><p><strong>Setting: </strong>Nonrandomized, open-label, multicenter phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Bictegravir exposure was lower during pregnancy compared with postpartum, yet C 24 concentrations were greater than the bictegravir protein-adjusted 95% effective concentration.</p>\",\"PeriodicalId\":14588,\"journal\":{\"name\":\"JAIDS Journal of Acquired Immune Deficiency Syndromes\",\"volume\":\" \",\"pages\":\"300-307\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798693/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAIDS Journal of Acquired Immune Deficiency Syndromes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/QAI.0000000000003571\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAIDS Journal of Acquired Immune Deficiency Syndromes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/QAI.0000000000003571","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Pharmacokinetics and Safety of Bictegravir in Pregnant and Postpartum Persons With HIV and Their Infants.
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.
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.
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