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The objective of this study was to investigate whether ageing leads to clinically relevant pharmacokinetic changes of antiretrovirals that would support a dose adjustment based on the age of the treated PLWH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma concentrations for 10 first\u2010line antiretrovirals were obtained in PLWH \u226555 years, participating in the Swiss HIV Cohort Study, and used to proof the predictive performance of our physiologically based pharmacokinetic (PBPK) model. The verified PBPK model predicted the continuous effect of ageing on HIV drug pharmacokinetics across adulthood (20\u201399 years). The impact of ethnicity on age\u2010related pharmacokinetic changes between whites and other races was statistically analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinically observed concentration\u2013time profiles of all investigated antiretrovirals were generally within the 95% confidence interval of the PBPK simulations, demonstrating the predictive power of the modelling approach used. The predicted decline in drug clearance drove age\u2010related pharmacokinetic changes of antiretrovirals, resulting in a maximal 70% [95% confidence interval: 40%, 120%] increase in antiretrovirals exposure across adulthood. Peak concentration, time to peak concentration and apparent volume of distribution were predicted to be unaltered by ageing. There was no statistically significant difference of age\u2010related pharmacokinetic changes between studied ethnicities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dose adjustment for antiretrovirals based on the age of male and female PLWH is<jats:italic>a priori<\/jats:italic>not necessary in the absence of severe comorbidities considering the large safety margin of the current first\u2010line HIV treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14402","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T19:05:20Z","timestamp":1590779120000},"page":"458-470","source":"Crossref","is-referenced-by-count":21,"title":["Effect of ageing on antiretroviral drug pharmacokinetics using clinical data combined with modelling and 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Pharmacology Institute of Translational Medicine University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Battegay","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research University Hospital Basel, Basel Switzerland"},{"name":"University of Basel Basel 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":"Melissa A.","family":"Penny","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel Switzerland"},{"name":"University of Basel Basel 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