{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:24:24Z","timestamp":1793291064544,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:00:00Z","timestamp":1706918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss National Foundation","award":["188504"],"award-info":[{"award-number":["188504"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Obesity is increasingly prevalent among people with human immunodeficiency virus (HIV, PWH). Obesity can reduce drug exposure; however, limited data are available for long-acting (LA) antiretrovirals. We performed in silico trials using physiologically based pharmacokinetic (PBPK) modeling to determine the effect of obesity on the exposure of LA cabotegravir and rilpivirine after the initial injection and after multiple injections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Our PBPK model was verified against available clinical data for LA cabotegravir and rilpivirine in normal weight\/ overweight (body mass index [BMI] &amp;lt;30\u2005kg\/m2) and in obese (BMI &amp;gt;30\u2005kg\/m2). Cohorts of virtual individuals were generated to simulate the exposure of LA cabotegravir\/rilpivirine up to a BMI of 60\u2005kg\/m2. The fold change in LA cabotegravir and rilpivirine exposures (area under the curve [AUC]) and trough concentrations (Cmin) for monthly and bimonthly administration were calculated for various BMI categories relative to normal weight (18.5\u201325\u2005kg\/m2).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Obesity was predicted to impact more cabotegravir than rilpivirine with a decrease in cabotegravir AUC and Cmin of &amp;gt;35% for BMI &amp;gt;35\u2005kg\/m2 and in rilpivirine AUC and Cmin of &amp;gt;18% for BMI &amp;gt;40\u2005kg\/m2 at steady-state. A significant proportion of morbidly obese individuals were predicted to have both cabotegravir and rilpivirine Cmin below the target concentration at steady-state with the bimonthly administration, but this was less frequent with the monthly administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Morbidly obese PWH are at risk of presenting suboptimal Cmin for cabotegravir\/rilpivirine after the first injection but also at steady-state particularly with the bimonthly administration. Therapeutic drug monitoring is advised to guide dosing interval adjustment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae060","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T12:56:57Z","timestamp":1706878617000},"page":"477-486","source":"Crossref","is-referenced-by-count":22,"title":["Effect of Obesity on the Exposure of Long-acting Cabotegravir and Rilpivirine: A Modeling Study"],"prefix":"10.1093","volume":"79","author":[{"given":"Sara","family":"Bettonte","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel , Basel , Switzerland"},{"name":"Faculty of Medicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Berton","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel , Basel , Switzerland"},{"name":"Faculty of Medicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Stader","sequence":"additional","affiliation":[{"name":"Certara UK Limited , Sheffield , United Kingdom"}],"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":"Faculty of Medicine, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-7050","authenticated-orcid":false,"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel , Basel , Switzerland"},{"name":"Faculty of Medicine, University of Basel , Basel , Switzerland"},{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool , Liverpool , United Kingdom"},{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, University Hospital Lausanne and University of Lausanne , Lausanne , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"2024081609305019900_ciae060-B1","author":"World Health Organization"},{"key":"2024081609305019900_ciae060-B2","author":"World Health Organization"},{"key":"2024081609305019900_ciae060-B3","doi-asserted-by":"crossref","first-page":"ofu040","DOI":"10.1093\/ofid\/ofu040","article-title":"Obesity trends and body mass index changes after starting antiretroviral treatment: the 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pharmacokinetic modeling in regulatory decision-making at the European Medicines Agency","volume":"102","author":"Luzon","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"2024081609305019900_ciae060-B13","doi-asserted-by":"crossref","first-page":"ofad361","DOI":"10.1093\/ofid\/ofad361","article-title":"Impact of obesity on the drug-drug interaction between dolutegravir and rifampicin or any other strong inducers","volume":"10","author":"Berton","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2024081609305019900_ciae060-B14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/YIC.0b013e32833948fa","article-title":"Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study","volume":"25","author":"Gopal","year":"2010","journal-title":"Int Clin 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analysis of rilpivirine in HIV-1-infected individuals","volume":"61","author":"Aouri","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2024081609305019900_ciae060-B29","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s40262-021-01005-1","article-title":"Pharmacokinetics and drug-drug interactions of long-acting intramuscular cabotegravir and rilpivirine","volume":"60","author":"Hodge","year":"2021","journal-title":"Clin Pharmacokinet"},{"key":"2024081609305019900_ciae060-B30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.antiviral.2014.05.009","article-title":"Etravirine plasma exposure is associated with virological efficacy in treatment-experienced HIV-positive patients","volume":"108","author":"Calcagno","year":"2014","journal-title":"Antiviral Res"},{"key":"2024081609305019900_ciae060-B31","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/cid\/ciae016","article-title":"Virological failure after switch to 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