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To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct\u2010acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV\u2010infected population.<\/jats:p>","DOI":"10.1002\/psp4.12604","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T07:43:04Z","timestamp":1627026184000},"page":"826-838","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy"],"prefix":"10.1002","volume":"10","author":[{"given":"Xavier","family":"Woot de Trixhe","sequence":"first","affiliation":[{"name":"Janssen R&amp;D Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Krzyzanski","sequence":"additional","affiliation":[{"name":"University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Janssen R&amp;D Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jos\u00e9","family":"Perez\u2010Ruixo","sequence":"additional","affiliation":[{"name":"Janssen R&amp;D Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.116"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.35"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5386.103"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24272"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1137\/080714579"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203110110"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2013.04.012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2015.04.017"},{"key":"e_1_2_8_11_1","volume-title":"Monolix version 2018 R2","author":"Lixoft","year":"2016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27202"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.08.034"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-014-9363-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5973-3_5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04082"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1201\/b18041"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5424.110"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13594-13605.2005"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.12604","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T17:47:40Z","timestamp":1693244860000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.12604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":18,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/psp4.12604"],"URL":"https:\/\/doi.org\/10.1002\/psp4.12604","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,23]]},"assertion":[{"value":"2020-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}