{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:28:24Z","timestamp":1791912504926,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:p>\n                    Antiviral treatments against hepatitis B virus (HBV) suppress viral replication but do not eradicate the virus, and need therefore to be taken lifelong to avoid relapse. Mathematical models can be useful to support the development of curative anti\u2010HBV agents; however, they mostly focus on short\u2010term HBV DNA data and neglect the complex host\u2010pathogen interaction. This work aimed to characterize the effect of treatment with lamivudine and\/or pegylated interferon (Peg\u2010IFN) in 1,300 patients (hepatitis B envelope antigen (HBeAg)\u2013positive and HBeAg\u2010negative) treated for 1\u2009year. A mathematical model was developed incorporating two populations of infected cells, namely , with a high transcriptional activity, that progressively evolve into , at a rate , representing cells with integrated HBV DNA that have a lower transcriptional activity. Parameters of the model were estimated in patients treated with lamivudine or Peg\u2010IFN alone (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a0894), and the model was then validated in patients treated with lamivudine plus Peg\u2010IFN (\n                    <jats:italic>N<\/jats:italic>\n                    \u00a0=\u00a0436) to predict the virological response after a year of combination treatment. Lamivudine had a larger effect in blocking viral production than Peg\u2010IFN (99.4\u201399.9% vs. 91.8\u201395.1%); however, Peg\u2010IFN had a significant immunomodulatory effect, leading to an enhancement of the loss rates of  (\u00d71.7 in HBeAg\u2010positive patients),  (&gt; \u00d77 irrespective of HBeAg status), and  (\u00d74.6 and \u00d72.0 in HBeAg\u2010positive and HBeAg\u2010negative patients, respectively). Using this model, we were able to describe the synergy of the different effects occurring during treatment with combination and predicted an effect of 99.99% on blocking viral production. This framework can therefore support the optimization of combination therapy with new anti\u2010HBV agents.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2798","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T04:47:06Z","timestamp":1669006026000},"page":"390-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Semi\u2010mechanistic Model to Characterize the Long\u2010Term Dynamics of Hepatitis B Virus Markers During Treatment With Lamivudine and Pegylated Interferon"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-7798","authenticated-orcid":false,"given":"Selma","family":"El Messaoudi","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Infection, Antimicrobials, Modelling, Evolution  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Lemenuel\u2010Diot","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, Roche Innovation Center  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Infection, Antimicrobials, Modelling, Evolution  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-5482","authenticated-orcid":false,"given":"J\u00e9r\u00e9mie","family":"Guedj","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Infection, Antimicrobials, Modelling, Evolution  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"Global progress report on HIV viral hepatitis and sexually transmitted infections<https:\/\/www.who.int\/publications\u2010detail\u2010redirect\/9789240027077>. 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