{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:26:02Z","timestamp":1789881962606,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The combination of sofosbuvir (<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>) plus an <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A inhibitor are rapidly decreasing, the combination of these <jats:styled-content style=\"fixed-case\">DAA<\/jats:styled-content>s will be the standard treatment in most low\u2010 to middle\u2010income countries in the future.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To identify key predictors of response that can be used to tailor treatment decisions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort of 216 consecutive patients infected with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (<jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content>) + daclatasvir (n = 176) or <jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The overall <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content> rate was high (94.4%; n = 204), regardless of the time to viral suppression or low\u2010level viraemia at the end of treatment. The model\u2010based predicted <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> levels at the end of treatment could not differentiate patients who did from those who did not achieve <jats:styled-content style=\"fixed-case\">SVR<\/jats:styled-content>. The presence of <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A resistance\u2010associated substitutions [position 28 (OR = 70.3, <jats:italic>P<\/jats:italic>&lt;.001) and\/or 31 (OR = 61.6, <jats:italic>P<\/jats:italic> = .002)] at baseline was predictive of virological failure in cirrhotic patients but was not associated with on\u2010treatment viral kinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This real\u2010world study confirms the excellent results of clinical trials with therapies based on a combination of <jats:styled-content style=\"fixed-case\">SOF<\/jats:styled-content> plus an <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A inhibitor. It suggests that a personalized approach including baseline <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A inhibitor resistance testing may inform treatment decisions in cirrhotic patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.14478","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T20:33:45Z","timestamp":1514061225000},"page":"665-673","source":"Crossref","is-referenced-by-count":19,"title":["Viral kinetics analysis and virological characterization of treatment failures in patients with chronic hepatitis C treated with sofosbuvir and an <scp>NS<\/scp>5A inhibitor"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-5467","authenticated-orcid":false,"given":"S.","family":"Fourati","sequence":"first","affiliation":[{"name":"Department of Virology Henri Mondor Hospital National Reference Center for Viral Hepatitis B, C and D University of Paris\u2010Est Cr\u00e9teil France"},{"name":"INSERM U955 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Guedj","sequence":"additional","affiliation":[{"name":"INSERM U1137 IAME Paris France"},{"name":"Universit\u00e9 Paris Diderot Sorbonne Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Chevaliez","sequence":"additional","affiliation":[{"name":"Department of Virology Henri Mondor Hospital National Reference Center for Viral Hepatitis B, C and D University of Paris\u2010Est Cr\u00e9teil France"},{"name":"INSERM U955 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. H. T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"INSERM U1137 IAME Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Roudot\u2010Thoraval","sequence":"additional","affiliation":[{"name":"Department of Public Health Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Ruiz","sequence":"additional","affiliation":[{"name":"INSERM U955 Cr\u00e9teil France"},{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Soulier","sequence":"additional","affiliation":[{"name":"Department of Virology Henri Mondor Hospital National Reference Center for Viral Hepatitis B, C and D University of Paris\u2010Est Cr\u00e9teil France"},{"name":"INSERM U955 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Scoazec","sequence":"additional","affiliation":[{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Varaut","sequence":"additional","affiliation":[{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Poiteau","sequence":"additional","affiliation":[{"name":"Department of Virology Henri Mondor Hospital National Reference Center for Viral Hepatitis B, C and D University of Paris\u2010Est Cr\u00e9teil France"},{"name":"INSERM U955 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Francois","sequence":"additional","affiliation":[{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mallat","sequence":"additional","affiliation":[{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"H\u00e9zode","sequence":"additional","affiliation":[{"name":"Department of Hepatology Henri Mondor Hospital University of Paris\u2010Est Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010M.","family":"Pawlotsky","sequence":"additional","affiliation":[{"name":"Department of Virology Henri Mondor Hospital National Reference Center for Viral Hepatitis B, C and D University of Paris\u2010Est Cr\u00e9teil France"},{"name":"INSERM U955 Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.08.043"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306218"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503153"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70050-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"e_1_2_7_8_1","unstructured":"J Hepatol 2016 EASL recommendations on treatment of hepatitis C 2016"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27826"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.01.007"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.04.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.06.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203110110"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02611-14"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.97"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28491"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29005"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27726"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ170"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13165"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.12.034"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.14478","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.14478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T13:41:40Z","timestamp":1695044500000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.14478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,22]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/apt.14478"],"URL":"https:\/\/doi.org\/10.1111\/apt.14478","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,22]]}}}