{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:50:45Z","timestamp":1784026245625,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017420","name":"Penta Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017420","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006209","name":"Radboudumc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pregnancy is associated with physiological changes, resulting in altered pharmacokinetics, which may impact antiretroviral drug exposure. To assure health and prevent vertical transmission of HIV, it is imperative to reach adequate drug exposure. This study aims to determine the impact of pregnancy on bictegravir pharmacokinetics, examine mechanisms responsible for lower exposure, report on placental transfer, safety, and efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This open-label pharmacokinetic study, included women living with HIV who used bictegravir, emtricitabine with tenofovir alafenamide. Plasma samples were obtained in third trimester, as well as 4\u20136 weeks postpartum. If feasible, cord blood and maternal plasma at delivery were obtained.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixteen participants were included. Geometric mean area under the curve for total bictegravir was 48.8\u2005mg*h\/L (coefficient of variation (CV) 25.9%) in third trimester and 99.2\u2005mg*L\/h (CV 32.9%) postpartum, with a geometric mean ratio (90% CI) of 0.49 (0.44\u20130.55); 24\u2005h post-dosing, median (IQR) unbound fractions were 0.15 (0.13\u20130.18)% and 0.11 (0.10\u20130.13) during pregnancy and postpartum, respectively. Median (IQR) ratio between pregnancy and postpartum was 173.7% (127.8\u2013305.7) for glucuronidation-metabolite (M15) and 200.7% (150.0\u2013224.9) for sulfation-metabolite (M20). Low-level viraemia was noted in several participants, but no vertical transmission occurred. Cord blood maternal plasma ratio (IQR) was 1.3 (1.0\u20131.4). No congenital anomalies were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although bictegravir exposure is decreased during pregnancy, mainly due to altered protein binding and increased glucuronidation and sulfation, trough levels remained above the PA-IC95. No vertical transmission occurred and no congenital anomalities were observed. Bictegravir was shown to have profound placental transfer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag159","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:43:15Z","timestamp":1776944595000},"source":"Crossref","is-referenced-by-count":1,"title":["Exploring the pharmacokinetic mechanisms that affect bictegravir exposure during pregnancy"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8674-1448","authenticated-orcid":false,"given":"L","family":"van der Wekken-Pas","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmacology and Toxicology, Radboudumc , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-5728","authenticated-orcid":false,"given":"C","family":"Hidalgo-Tenorio","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen de las Nieves, Instituto de Investigaci\u00f3n Biosanitario de Granada (IBS-Grana), Granada, Spain Infectious Diseases Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J K","family":"Rockstroh","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Bonn, Bonn, Germany Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"van Bremen","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Bonn, Bonn, Germany Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Richel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboudumc , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4564-1963","authenticated-orcid":false,"given":"J","family":"Molto","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitari Germans Trias I Pujol and Fundaci\u00f3 Lluita Contra les Infeccions, Badalona, Spain and CIBERINFEC, Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J S","family":"Lambert","sequence":"additional","affiliation":[{"name":"Saint James Hospital, Dublin, Ireland Department of Infectious Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"de Kanter","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Cura\u00e7ao Medical Center , Willemstad, Cura\u00e7ao"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Konopnicki","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Saint-Pierre University Hospital , Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-2818","authenticated-orcid":false,"given":"D","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology and Toxicology, Radboudumc , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-9934","authenticated-orcid":false,"given":"A","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmacology and Toxicology, Radboudumc , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026050611255571000_dkag159-B1","author":"World Health Organisation"},{"key":"2026050611255571000_dkag159-B2","doi-asserted-by":"publisher","first-page":"849","DOI":"10.3390\/v15040849","article-title":"Prevention of the vertical transmission of HIV; A recap of the journey so far","volume":"15","author":"Cardenas","year":"2023","journal-title":"Viruses"},{"key":"2026050611255571000_dkag159-B3","author":"European AIDS Clinical Society"},{"key":"2026050611255571000_dkag159-B4","author":"Panel on Treatment of HIV in Pregnancy and Prevention of Perinatal Transmission"},{"key":"2026050611255571000_dkag159-B5","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1097\/QAD.0000000000003032","article-title":"First pharmacokinetic data of bictegravir in pregnant women living with HIV","volume":"35","author":"Bukkems","year":"2021","journal-title":"AIDS"},{"key":"2026050611255571000_dkag159-B6","doi-asserted-by":"publisher","first-page":"F1","DOI":"10.1097\/QAD.0000000000003783","article-title":"A study of the pharmacokinetics, safety, and efficacy of bictegravir\/emtricitabine\/tenofovir alafenamide in virologically suppressed pregnant women with HIV","volume":"38","author":"Zhang","year":"2024","journal-title":"AIDS"},{"key":"2026050611255571000_dkag159-B7","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/QAI.0000000000003571","article-title":"Pharmacokinetics and safety of bictegravir in pregnant and postpartum persons with HIV and their infants","volume":"98","author":"Powis","year":"2025","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026050611255571000_dkag159-B8","doi-asserted-by":"publisher","first-page":"989","DOI":"10.2165\/00003088-200544100-00001","article-title":"Pregnancy-induced changes in pharmacokinetics","volume":"44","author":"Anderson","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"2026050611255571000_dkag159-B9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s11095-018-2352-2","article-title":"Pregnancy-associated changes in pharmacokinetics and their clinical implications","volume":"35","author":"Koren","year":"2018","journal-title":"Pharm Res"},{"key":"2026050611255571000_dkag159-B10","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.70134","article-title":"Population pharmacokinetics of bictegravir during pregnancy and postpartum: role of adherence in maintaining therapeutic exposure","volume":"66","author":"Sun","year":"2026","journal-title":"J Clin Pharmacol"},{"key":"2026050611255571000_dkag159-B11","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1097\/QAD.0000000000002637","article-title":"Placental transfer of the integrase strand inhibitors cabotegravir and bictegravir in the ex-vivo human cotyledon perfusion model","volume":"34","author":"Pencol\u00e9","year":"2020","journal-title":"AIDS"},{"key":"2026050611255571000_dkag159-B12","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1093\/jac\/dkab424","article-title":"Bictegravir pharmacokinetics in a late-presenting HIV-1-infected pregnant woman: a case report","volume":"77","author":"L\u00ea","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2026050611255571000_dkag159-B13","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jchromb.2018.12.008","article-title":"Development and validation of an UPLC-MS\/MS bioanalytical method for simultaneous quantification of the antiretroviral drugs dolutegravir, elvitegravir, raltegravir, nevirapine and etravirine in human plasma","volume":"1105","author":"Bollen","year":"2019","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2026050611255571000_dkag159-B14","doi-asserted-by":"publisher","first-page":"115832","DOI":"10.1016\/j.jpba.2023.115832","article-title":"Development, validation and clinical implementation of a UPLC-MS\/MS bioanalytical method for simultaneous quantification of cabotegravir and rilpivirine E-isomer in human plasma","volume":"238","author":"Bevers","year":"2024","journal-title":"J Pharm Biomed Anal"},{"key":"2026050611255571000_dkag159-B15","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1128\/AAC.46.3.884-886.2002","article-title":"International interlaboratory quality control program for measurement of antiretroviral drugs in plasma","volume":"46","author":"Aarnoutse","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"key":"2026050611255571000_dkag159-B16","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1097\/00126334-200303010-00007","article-title":"Brief report: evaluation of antiretroviral drug measurements by an interlaboratory quality control program","volume":"32","author":"Droste","year":"2003","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026050611255571000_dkag159-B17","author":"U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases"},{"key":"2026050611255571000_dkag159-B18","author":"European Medicines Agency"},{"issue":"9\u201311","key":"2026050611255571000_dkag159-B19","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1080\/00498254.2022.2159569","article-title":"Human and nonclinical disposition of [14C]bictegravir, a potent integrase strand-transfer inhibitor for the treatment of HIV-1 infection","volume":"52","author":"Subramanian","year":"2022","journal-title":"Xenobiotica Fate Foreign Compd Biol Syst"},{"key":"2026050611255571000_dkag159-B20","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1093\/cid\/cix534","article-title":"Lowered rilpivirine exposure during the third trimester of pregnancy in human immunodeficiency virus type 1-infected women","volume":"65","author":"Schalkwijk","year":"2017  15","journal-title":"Clin Infect Dis"},{"key":"2026050611255571000_dkag159-B21","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1093\/cid\/civ366","article-title":"Raltegravir in HIV-1-infected pregnant women: pharmacokinetics, safety, and efficacy","volume":"61","author":"Blonk","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2026050611255571000_dkag159-B22","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1097\/QAD.0000000000002767","article-title":"Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV","volume":"35","author":"Brooks","year":"2021","journal-title":"AIDS"},{"key":"2026050611255571000_dkag159-B23","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1093\/cid\/ciab1010","article-title":"Tenofovir alafenamide plasma concentrations are reduced in pregnant women living with human immunodeficiency virus (HIV): data from the PANNA network","volume":"75","author":"Bukkems","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2026050611255571000_dkag159-B24","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1111\/j.1468-1293.2011.00965.x","article-title":"Effect of pregnancy on emtricitabine pharmacokinetics","volume":"13","author":"Stek","year":"2012","journal-title":"HIV Med"},{"key":"2026050611255571000_dkag159-B25","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1097\/QAD.0b013e32835c208b","article-title":"The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women","volume":"27","author":"Colbers","year":"2013","journal-title":"AIDS"},{"key":"2026050611255571000_dkag159-B26","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1093\/cid\/ciae218","article-title":"Bictegravir use during pregnancy: a multicenter retrospective analysis evaluating HIV viral suppression and perinatal outcomes","volume":"79","author":"Holt","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2026050611255571000_dkag159-B27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1097\/QAI.0000000000003708","article-title":"Perinatal and early infant outcomes after bictegravir exposure in pregnancy: a Canadian surveillance study","volume":"100","author":"Wong","year":"2025","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026050611255571000_dkag159-B28","author":"European AIDS Clinical Society"},{"key":"2026050611255571000_dkag159-B29","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1097\/QAI.0000000000002830","article-title":"Optimizing dolutegravir initiation in neonates using population pharmacokinetic modeling and simulation","volume":"89","author":"Piscitelli","year":"2022","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026050611255571000_dkag159-B30","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-086543","article-title":"Cohort profile: the Swiss mother and child HIV cohort study (MoCHiV)","volume":"14","author":"Paioni","year":"2024","journal-title":"BMJ Open"},{"key":"2026050611255571000_dkag159-B31","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25846","article-title":"Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project","volume":"24","author":"Lyerly","year":"2021","journal-title":"J Int AIDS Soc"},{"key":"2026050611255571000_dkag159-B32","author":"National Academies of Sciences, Engineering, and Medicine"},{"key":"2026050611255571000_dkag159-B33"},{"key":"2026050611255571000_dkag159-B34","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.26401","article-title":"Evaluation of long-acting cabotegravir safety and pharmacokinetics in pregnant women in Eastern and Southern Africa: a secondary analysis of HPTN 084","volume":"28","author":"Delany-Moretlwe","year":"2025","journal-title":"J Int AIDS Soc"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/6\/dkag159\/68229994\/dkag159.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/6\/dkag159\/68229994\/dkag159.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:26:02Z","timestamp":1778081162000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag159\/8671051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag159","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,5]]},"article-number":"dkag159"}}