{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:33:35Z","timestamp":1782369215208,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Clinical studies in aging people living with HIV (PLWH) are sparse for the novel integrase inhibitor bictegravir, leading to some uncertainty about dosing recommendations for elderly PLWH. The objective of this study was to investigate the continuous impact of aging on bictegravir pharmacokinetics by combining clinically observed data with modeling to support a safe and efficient anti\u2010HIV therapy with advanced age. A physiologically\u2010based pharmacokinetic (PBPK) model was developed for bictegravir with clinically observed data from phase I studies. The predictive model performance was verified using bictegravir plasma concentrations sampled as part of the general therapeutic drug monitoring (TDM) program of the Swiss HIV Cohort Study in young (20\u201355\u00a0years) and elderly PLWH (55\u201385\u00a0years). The verified PBPK model subsequently predicted the continuous impact of aging on bictegravir pharmacokinetics across adulthood (20\u201399\u00a0years). Bictegravir exposure was unchanged in elderly compared with young PLWH when analyzing the TDM data of the Swiss HIV Cohort Study. PBPK simulations predicted clinically observed data from 60 young and 32 elderly PLWH mostly within the 95% confidence interval, demonstrating the predictive power of the used modeling approach. Simulations predicted drug exposure to increase up to 40% during adulthood, which was not statistically significantly different from the age\u2010related pharmacokinetic changes of other HIV and non\u2010HIV drugs. Sex had no impact on the age\u2010related changes of bictegravir pharmacokinetics. Considering the safety margin of bictegravir, a dose adjustment for the novel integrase inhibitor is<jats:italic>a priori<\/jats:italic>not necessary in elderly PLWH in the absence of severe comorbidities.<\/jats:p>","DOI":"10.1002\/cpt.2178","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T07:01:36Z","timestamp":1612162896000},"page":"1025-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Physiologically\u2010Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV"],"prefix":"10.1111","volume":"109","author":[{"given":"Felix","family":"Stader","sequence":"first","affiliation":[{"name":"Departments of Medicine and Clinical Research University Hospital Basel Basel Switzerland"},{"name":"University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Courlet","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Battegay","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Clinical Research University Hospital Basel Basel Switzerland"},{"name":"University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Clinical Research University Hospital Basel Basel Switzerland"},{"name":"University of Basel Basel Switzerland"},{"name":"Department of Molecular and Clinical Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0896-4"},{"key":"e_1_2_10_2_1","unstructured":"European Medicines Agency.Biktavry<https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/biktarvy> (2018). Accessed May 6 2020."},{"key":"e_1_2_10_3_1","unstructured":"AIDSinfo.Department of Health and Human Services Adults and Adolescents Antiretroviral Guidelines Panel* Classifies a Fixed\u2010Dose Combination Product of Bictegravir\/Tenofovir Alafenamide\/Emtricitabine as One of the Recommended Initial Regimens for Most People with HIV<https:\/\/aidsinfo.nih.gov> (2018). Accessed May 6 2020."},{"key":"e_1_2_10_4_1","unstructured":"European AIDS Clinical Society.European AIDS Clinical Society Guidelines Version 10.0<https:\/\/www.eacsociety.org\/files\/2019_guidelines\u201010.0_final.pdf> (2019). Accessed December 15 2019."},{"key":"e_1_2_10_5_1","unstructured":"U.S. Food and Drug Administration.BIKTARVY. Highlights of prescribing information<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210251s000lbl.pdf> (2018). 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Pharmacol."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(99)00147-7"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20322"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20502"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9210-3"},{"key":"e_1_2_10_17_1","first-page":"A74\u2010A","article-title":"P176 Clinical pharmacology of the HIV integrase strand transfer inhibitor bictegravir","volume":"93","author":"Zhang H.","year":"2017","journal-title":"Sex. Transmitted Infect."},{"key":"e_1_2_10_18_1","unstructured":"U.S. Food and Drug Administration.Physiologically based pharmacokinetic analysis \u2010 format and content. Guidance for industry <https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM531207.pdf> (2016). 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