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Virological patterns of HCV patients with failure to interferon‐free regimens
The study characterized the virological patterns and the resistance‐associated substitutions (RASs) in patients with failure to IFN‐free regimens enrolled in the real‐life setting. All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania...
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Published in: | Journal of medical virology 2018-05, Vol.90 (5), p.942-950 |
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creator | Starace, Mario Minichini, Carmine De Pascalis, Stefania Macera, Margherita Occhiello, Laura Messina, Vincenzo Sangiovanni, Vincenzo Adinolfi, Luigi E. Claar, Ernesto Precone, Davide Stornaiuolo, Gianfranca Stanzione, Maria Ascione, Tiziana Caroprese, Mara Zampino, Rosa Parrilli, Gianpaolo Gentile, Ivan Brancaccio, Giuseppina Iovinella, Vincenzo Martini, Salvatore Masarone, Mario Fontanella, Luca Masiello, Addolorata Sagnelli, Evangelista Punzi, Rodolfo Salomone Megna, Angelo Santoro, Renato Gaeta, Giovanni B. Coppola, Nicola |
description | The study characterized the virological patterns and the resistance‐associated substitutions (RASs) in patients with failure to IFN‐free regimens enrolled in the real‐life setting. All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home‐made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub‐optimal DAA regimen, 19 with a simeprevir‐based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub‐optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8‐57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub‐optimal regimen group (12.5%, P |
doi_str_mv | 10.1002/jmv.25022 |
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All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home‐made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub‐optimal DAA regimen, 19 with a simeprevir‐based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub‐optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8‐57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub‐optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0‐25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir‐based regimen group (31.6%) and sub‐optimal regimen group (18.7%). In our real‐life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.25022</identifier><identifier>PMID: 29315640</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Antiviral Agents - administration & dosage ; antiviral therapy ; chronic HCV hepatitis ; DAA failure ; DAAs ; Drug Resistance, Viral ; Female ; Genetic Variation ; Genotype ; Genotypes ; Hepacivirus - classification ; Hepacivirus - genetics ; Hepacivirus - isolation & purification ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - virology ; Hospitals, University ; Humans ; Interferon ; Italy ; Male ; Microbiology ; Middle Aged ; Mutation, Missense ; Patients ; Prevalence ; RASs ; Sequence Analysis, DNA ; Treatment Failure ; Viral Nonstructural Proteins - genetics ; Virology</subject><ispartof>Journal of medical virology, 2018-05, Vol.90 (5), p.942-950</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-76eb05b03476fc062e681fbe9df4ca727def820c3e779f802d8a7a38dd9b8c523</citedby><cites>FETCH-LOGICAL-c3532-76eb05b03476fc062e681fbe9df4ca727def820c3e779f802d8a7a38dd9b8c523</cites><orcidid>0000-0001-5897-4949 ; 0000-0003-2817-8436</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29315640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Starace, Mario</creatorcontrib><creatorcontrib>Minichini, Carmine</creatorcontrib><creatorcontrib>De Pascalis, Stefania</creatorcontrib><creatorcontrib>Macera, Margherita</creatorcontrib><creatorcontrib>Occhiello, Laura</creatorcontrib><creatorcontrib>Messina, Vincenzo</creatorcontrib><creatorcontrib>Sangiovanni, Vincenzo</creatorcontrib><creatorcontrib>Adinolfi, Luigi E.</creatorcontrib><creatorcontrib>Claar, Ernesto</creatorcontrib><creatorcontrib>Precone, Davide</creatorcontrib><creatorcontrib>Stornaiuolo, Gianfranca</creatorcontrib><creatorcontrib>Stanzione, Maria</creatorcontrib><creatorcontrib>Ascione, Tiziana</creatorcontrib><creatorcontrib>Caroprese, Mara</creatorcontrib><creatorcontrib>Zampino, Rosa</creatorcontrib><creatorcontrib>Parrilli, Gianpaolo</creatorcontrib><creatorcontrib>Gentile, Ivan</creatorcontrib><creatorcontrib>Brancaccio, Giuseppina</creatorcontrib><creatorcontrib>Iovinella, Vincenzo</creatorcontrib><creatorcontrib>Martini, Salvatore</creatorcontrib><creatorcontrib>Masarone, Mario</creatorcontrib><creatorcontrib>Fontanella, Luca</creatorcontrib><creatorcontrib>Masiello, Addolorata</creatorcontrib><creatorcontrib>Sagnelli, Evangelista</creatorcontrib><creatorcontrib>Punzi, Rodolfo</creatorcontrib><creatorcontrib>Salomone Megna, Angelo</creatorcontrib><creatorcontrib>Santoro, Renato</creatorcontrib><creatorcontrib>Gaeta, Giovanni B.</creatorcontrib><creatorcontrib>Coppola, Nicola</creatorcontrib><title>Virological patterns of HCV patients with failure to interferon‐free regimens</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>The study characterized the virological patterns and the resistance‐associated substitutions (RASs) in patients with failure to IFN‐free regimens enrolled in the real‐life setting. All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home‐made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub‐optimal DAA regimen, 19 with a simeprevir‐based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub‐optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8‐57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub‐optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0‐25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir‐based regimen group (31.6%) and sub‐optimal regimen group (18.7%). In our real‐life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amino Acid Substitution</subject><subject>Antiviral Agents - administration & dosage</subject><subject>antiviral therapy</subject><subject>chronic HCV hepatitis</subject><subject>DAA failure</subject><subject>DAAs</subject><subject>Drug Resistance, Viral</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Hepacivirus - classification</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - isolation & purification</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - virology</subject><subject>Hospitals, University</subject><subject>Humans</subject><subject>Interferon</subject><subject>Italy</subject><subject>Male</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Mutation, Missense</subject><subject>Patients</subject><subject>Prevalence</subject><subject>RASs</subject><subject>Sequence Analysis, DNA</subject><subject>Treatment Failure</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>Virology</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kL1OwzAURi0EoqUw8AIoEhNDyrWd2MmIKqCgoi7QNcrPdXGVxMVOqLrxCDwjT0JKChvT1ZWOzicdQs4pjCkAu15V72MWAmMHZEghFn4Mkh6SIdBA-ELQcEBOnFsBQBQzdkwGLOY0FAEMyXyhrSnNUudp6a3TpkFbO88obzpZ7H6NdeO8jW5ePZXqsrXoNcbTdccptKb--vhUFtGzuNQV1u6UHKm0dHi2vyPycnf7PJn6s_n9w-Rm5uc85MyXAjMIM-CBFCoHwVBEVGUYFyrIU8lkgSpikHOUMlYRsCJKZcqjooizKA8ZH5HL3ru25q1F1yQr09q6m0wYUM5kwMWOuuqp3BrnLKpkbXWV2m1CIdmlS7p0yU-6jr3YG9uswuKP_G3VAdc9sNElbv83JY9Pi175DdkCeSk</recordid><startdate>201805</startdate><enddate>201805</enddate><creator>Starace, Mario</creator><creator>Minichini, Carmine</creator><creator>De Pascalis, Stefania</creator><creator>Macera, Margherita</creator><creator>Occhiello, Laura</creator><creator>Messina, Vincenzo</creator><creator>Sangiovanni, Vincenzo</creator><creator>Adinolfi, Luigi E.</creator><creator>Claar, Ernesto</creator><creator>Precone, Davide</creator><creator>Stornaiuolo, Gianfranca</creator><creator>Stanzione, Maria</creator><creator>Ascione, Tiziana</creator><creator>Caroprese, Mara</creator><creator>Zampino, Rosa</creator><creator>Parrilli, Gianpaolo</creator><creator>Gentile, Ivan</creator><creator>Brancaccio, Giuseppina</creator><creator>Iovinella, Vincenzo</creator><creator>Martini, Salvatore</creator><creator>Masarone, Mario</creator><creator>Fontanella, Luca</creator><creator>Masiello, Addolorata</creator><creator>Sagnelli, Evangelista</creator><creator>Punzi, Rodolfo</creator><creator>Salomone Megna, Angelo</creator><creator>Santoro, Renato</creator><creator>Gaeta, Giovanni B.</creator><creator>Coppola, Nicola</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0001-5897-4949</orcidid><orcidid>https://orcid.org/0000-0003-2817-8436</orcidid></search><sort><creationdate>201805</creationdate><title>Virological patterns of HCV patients with failure to interferon‐free regimens</title><author>Starace, Mario ; Minichini, Carmine ; De Pascalis, Stefania ; Macera, Margherita ; Occhiello, Laura ; Messina, Vincenzo ; Sangiovanni, Vincenzo ; Adinolfi, Luigi E. ; Claar, Ernesto ; Precone, Davide ; Stornaiuolo, Gianfranca ; Stanzione, Maria ; Ascione, Tiziana ; Caroprese, Mara ; Zampino, Rosa ; Parrilli, Gianpaolo ; Gentile, Ivan ; Brancaccio, Giuseppina ; Iovinella, Vincenzo ; Martini, Salvatore ; Masarone, Mario ; Fontanella, Luca ; Masiello, Addolorata ; Sagnelli, Evangelista ; Punzi, Rodolfo ; Salomone Megna, Angelo ; Santoro, Renato ; Gaeta, Giovanni B. ; Coppola, Nicola</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-76eb05b03476fc062e681fbe9df4ca727def820c3e779f802d8a7a38dd9b8c523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amino Acid Substitution</topic><topic>Antiviral Agents - 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All 87 consecutive HCV patients with failed IFN‐free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home‐made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub‐optimal DAA regimen, 19 with a simeprevir‐based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub‐optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8‐57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub‐optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0‐25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir‐based regimen group (31.6%) and sub‐optimal regimen group (18.7%). In our real‐life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29315640</pmid><doi>10.1002/jmv.25022</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5897-4949</orcidid><orcidid>https://orcid.org/0000-0003-2817-8436</orcidid></addata></record> |
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subjects | Adult Aged Aged, 80 and over Amino Acid Substitution Antiviral Agents - administration & dosage antiviral therapy chronic HCV hepatitis DAA failure DAAs Drug Resistance, Viral Female Genetic Variation Genotype Genotypes Hepacivirus - classification Hepacivirus - genetics Hepacivirus - isolation & purification Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - virology Hospitals, University Humans Interferon Italy Male Microbiology Middle Aged Mutation, Missense Patients Prevalence RASs Sequence Analysis, DNA Treatment Failure Viral Nonstructural Proteins - genetics Virology |
title | Virological patterns of HCV patients with failure to interferon‐free regimens |
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