{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:28:33Z","timestamp":1791260913847,"version":"4.1.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Clin Microbiol"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of &lt;1 log IU\/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a &gt;3-fold shift in 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (\n            <jats:italic>P<\/jats:italic>\n            = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.\n          <\/jats:p>","DOI":"10.1128\/jcm.03633-14","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T02:21:46Z","timestamp":1430360506000},"page":"2195-2202","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin"],"prefix":"10.1128","volume":"53","author":[{"given":"Sylvie","family":"Larrat","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire Grenoble, P\u00f4le Biologie, Laboratoire de Virologie, D\u00e9partement des Agents Infectieux, Grenoble, France"},{"name":"Universit\u00e9 Grenoble Alpes, Unit of Virus Host Cell Interactions UMI 3265 UJF-EMBL-CNRS, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Vallet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Europ\u00e9enne de Bretagne, UFR M\u00e9decine et des Sciences de la Sant\u00e9, LUBEM, Brest, France"},{"name":"Laboratoire de Virologie, Centre Hospitalier R\u00e9gional Universitaire, Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"David-Tchouda","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Grenoble, P\u00f4le Recherche, Cellule d'\u00c9valuation M\u00e9dico-\u00c9conomique Innovation, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alban","family":"Caporossi","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Grenoble, P\u00f4le Biologie, Laboratoire de Virologie, D\u00e9partement des Agents Infectieux, Grenoble, France"},{"name":"Universit\u00e9 Grenoble Alpes, TIMC-IMAG\/CNRS\/UMR 5525, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Margier","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Grenoble, P\u00f4le Recherche, Cellule d'\u00c9valuation M\u00e9dico-\u00c9conomique Innovation, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Rami\u00e8re","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre de Biologie Nord, H\u00f4pital de la Croix Rousse, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Scholtes","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre de Biologie Nord, H\u00f4pital de la Croix Rousse, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Ha\u00efm-Boukobza","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Paul Brousse, Villejuif, France"},{"name":"INSERM U785, Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine Le Kremlin-Bic\u00eatre, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Roque-Afonso","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Paul Brousse, Villejuif, France"},{"name":"INSERM U785, Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine Le Kremlin-Bic\u00eatre, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Besse","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire H\u00f4tel Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Andr\u00e9-Garnier","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire H\u00f4tel Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiane","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Laboratoire Alphabio, H\u00f4pital Ambroise Par\u00e9, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Halfon","sequence":"additional","affiliation":[{"name":"Laboratoire Alphabio, H\u00f4pital Ambroise Par\u00e9, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Pivert","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie-Bact\u00e9riologie, Centre Hospitalier Universitaire Angers, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"LeGuillou-Guillemette","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie-Bact\u00e9riologie, Centre Hospitalier Universitaire Angers, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Abravanel","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire, Institut F\u00e9d\u00e9ratif de Biologie, INSERM U563, Centre Hospitalier Universitaire Toulouse Purpan, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Guivarch","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Centre Hospitalier Universitaire, Institut F\u00e9d\u00e9ratif de Biologie, INSERM U563, Centre Hospitalier Universitaire Toulouse Purpan, Toulouse, 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