Impact of resistance‐associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir
Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre‐existence of Y93 H resistance‐associated variants (RAVs) in the non‐structural protein 5A (NS5A) region. The aim o...
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| creator | Ikeda, Hiroki Watanabe, Tsunamasa Okuse, Chiaki Matsumoto, Nobuyuki Ishii, Toshiya Yamada, Norie Shigefuku, Ryuta Hattori, Nobuhiro Matsunaga, Kotaro Nakano, Hiroyasu Hiraishi, Tetsuya Kobayashi, Minoru Yasuda, Kiyomi Yamamoto, Hiroyuki Yasuda, Hiroshi Kurosaki, Masayuki Izumi, Namiki Yotsuyanagi, Hiroshi Suzuki, Michihiro Itoh, Fumio |
| description | Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre‐existence of Y93 H resistance‐associated variants (RAVs) in the non‐structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post‐treatment was possible. Pre‐treatment RAVs in the non‐structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)‐Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR‐Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1–25% in 5 patients, 26–75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of |
| doi_str_mv | 10.1002/jmv.24608 |
| format | Article |
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The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post‐treatment was possible. Pre‐treatment RAVs in the non‐structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)‐Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR‐Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1–25% in 5 patients, 26–75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of <1%, 1–25%, 26–75%, and ≥76% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (P < 0.0001). The dominancy of pre‐treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct‐acting antiviral agent treatments. J. Med. Virol. 89:99–105, 2017. © 2016 Wiley Periodicals, Inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.24608</identifier><identifier>PMID: 27329864</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antiviral Agents - therapeutic use ; asunaprevir ; Carbamates ; Clinical outcomes ; daclatasvir ; Drug Resistance, Viral ; Female ; Genotype ; Genotype & phenotype ; Genotyping Techniques ; HCV ; Hepacivirus - classification ; Hepacivirus - genetics ; Hepacivirus - isolation & purification ; Hepatitis ; Hepatitis C virus ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - virology ; Humans ; Imidazoles - therapeutic use ; Isoquinolines - therapeutic use ; Male ; Middle Aged ; Mutation, Missense ; Polymerase Chain Reaction ; Prospective Studies ; Pyrrolidines ; resistance‐associated variant ; Sulfonamides - therapeutic use ; Sustained Virologic Response ; sustained virological response ; Treatment Outcome ; Valine - analogs & derivatives ; Viral Nonstructural Proteins - genetics ; Virology</subject><ispartof>Journal of medical virology, 2017-01, Vol.89 (1), p.99-105</ispartof><rights>2016 Wiley Periodicals, Inc.</rights><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4568-61e36448c3bf8c58a5a4f3e188c82f2ec770e3d10fde56ea97f8894db37435b3</citedby><cites>FETCH-LOGICAL-c4568-61e36448c3bf8c58a5a4f3e188c82f2ec770e3d10fde56ea97f8894db37435b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.24608$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.24608$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27329864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ikeda, Hiroki</creatorcontrib><creatorcontrib>Watanabe, Tsunamasa</creatorcontrib><creatorcontrib>Okuse, Chiaki</creatorcontrib><creatorcontrib>Matsumoto, Nobuyuki</creatorcontrib><creatorcontrib>Ishii, Toshiya</creatorcontrib><creatorcontrib>Yamada, Norie</creatorcontrib><creatorcontrib>Shigefuku, Ryuta</creatorcontrib><creatorcontrib>Hattori, Nobuhiro</creatorcontrib><creatorcontrib>Matsunaga, Kotaro</creatorcontrib><creatorcontrib>Nakano, Hiroyasu</creatorcontrib><creatorcontrib>Hiraishi, Tetsuya</creatorcontrib><creatorcontrib>Kobayashi, Minoru</creatorcontrib><creatorcontrib>Yasuda, Kiyomi</creatorcontrib><creatorcontrib>Yamamoto, Hiroyuki</creatorcontrib><creatorcontrib>Yasuda, Hiroshi</creatorcontrib><creatorcontrib>Kurosaki, Masayuki</creatorcontrib><creatorcontrib>Izumi, Namiki</creatorcontrib><creatorcontrib>Yotsuyanagi, Hiroshi</creatorcontrib><creatorcontrib>Suzuki, Michihiro</creatorcontrib><creatorcontrib>Itoh, Fumio</creatorcontrib><title>Impact of resistance‐associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir</title><title>Journal of medical virology</title><addtitle>J Med Virol</addtitle><description>Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre‐existence of Y93 H resistance‐associated variants (RAVs) in the non‐structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post‐treatment was possible. Pre‐treatment RAVs in the non‐structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)‐Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR‐Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1–25% in 5 patients, 26–75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of <1%, 1–25%, 26–75%, and ≥76% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (P < 0.0001). The dominancy of pre‐treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct‐acting antiviral agent treatments. J. Med. Virol. 89:99–105, 2017. © 2016 Wiley Periodicals, Inc.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antiviral Agents - therapeutic use</subject><subject>asunaprevir</subject><subject>Carbamates</subject><subject>Clinical outcomes</subject><subject>daclatasvir</subject><subject>Drug Resistance, Viral</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Genotyping Techniques</subject><subject>HCV</subject><subject>Hepacivirus - classification</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - isolation & purification</subject><subject>Hepatitis</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - virology</subject><subject>Humans</subject><subject>Imidazoles - therapeutic use</subject><subject>Isoquinolines - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation, Missense</subject><subject>Polymerase Chain Reaction</subject><subject>Prospective Studies</subject><subject>Pyrrolidines</subject><subject>resistance‐associated variant</subject><subject>Sulfonamides - therapeutic use</subject><subject>Sustained Virologic Response</subject><subject>sustained virological response</subject><subject>Treatment Outcome</subject><subject>Valine - analogs & derivatives</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>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0c9u1DAQBnALUdFt4cALIEtc4JCu_8VxjmhVaFERl6rXaOJMileJE2xnq70h8QI8I09Sw5YekJA4eeT56ZNGHyEvOTvjjIn1dtydCaWZeUJWnNW6qFnFn5IV40oXWvPymJzEuGWMmVqIZ-RYVFLURqsV-X45zmATnXoaMLqYwFv8-e0HxDhZBwk7uoPgwCfaTaPzeb2nk6cpIKQR87fzdIbk8hjpnUtf6MXmht6in9J-RsrbnGvR7Zy_pR3YARLEnQtriIuHOWCen5OjHoaILx7eU3L9_vx6c1Fcff5wuXl3VVhValNojlIrZaxse2NLAyWoXiI3xhrRC7RVxVB2nPUdlhqhrnpjatW1slKybOUpeXOIncP0dcGYmtFFi8MAHqclNtworZhUTPwHFbpiXEiV6eu_6HZags93ZCWVqkxdVlm9PSgbphgD9s0c3Ahh33DW_OqwyR02vzvM9tVD4tKO2D3KP6VlsD6AOzfg_t9JzcdPN4fIe1LcqFg</recordid><startdate>201701</startdate><enddate>201701</enddate><creator>Ikeda, Hiroki</creator><creator>Watanabe, Tsunamasa</creator><creator>Okuse, Chiaki</creator><creator>Matsumoto, Nobuyuki</creator><creator>Ishii, Toshiya</creator><creator>Yamada, Norie</creator><creator>Shigefuku, Ryuta</creator><creator>Hattori, Nobuhiro</creator><creator>Matsunaga, Kotaro</creator><creator>Nakano, Hiroyasu</creator><creator>Hiraishi, Tetsuya</creator><creator>Kobayashi, Minoru</creator><creator>Yasuda, Kiyomi</creator><creator>Yamamoto, Hiroyuki</creator><creator>Yasuda, Hiroshi</creator><creator>Kurosaki, Masayuki</creator><creator>Izumi, Namiki</creator><creator>Yotsuyanagi, Hiroshi</creator><creator>Suzuki, Michihiro</creator><creator>Itoh, Fumio</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><scope>7X8</scope></search><sort><creationdate>201701</creationdate><title>Impact of resistance‐associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir</title><author>Ikeda, Hiroki ; Watanabe, Tsunamasa ; Okuse, Chiaki ; Matsumoto, Nobuyuki ; Ishii, Toshiya ; Yamada, Norie ; Shigefuku, Ryuta ; Hattori, Nobuhiro ; Matsunaga, Kotaro ; Nakano, Hiroyasu ; Hiraishi, Tetsuya ; Kobayashi, Minoru ; Yasuda, Kiyomi ; Yamamoto, Hiroyuki ; Yasuda, Hiroshi ; Kurosaki, Masayuki ; Izumi, Namiki ; Yotsuyanagi, Hiroshi ; Suzuki, Michihiro ; Itoh, Fumio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4568-61e36448c3bf8c58a5a4f3e188c82f2ec770e3d10fde56ea97f8894db37435b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antiviral Agents - 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Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ikeda, Hiroki</au><au>Watanabe, Tsunamasa</au><au>Okuse, Chiaki</au><au>Matsumoto, Nobuyuki</au><au>Ishii, Toshiya</au><au>Yamada, Norie</au><au>Shigefuku, Ryuta</au><au>Hattori, Nobuhiro</au><au>Matsunaga, Kotaro</au><au>Nakano, Hiroyasu</au><au>Hiraishi, Tetsuya</au><au>Kobayashi, Minoru</au><au>Yasuda, Kiyomi</au><au>Yamamoto, Hiroyuki</au><au>Yasuda, Hiroshi</au><au>Kurosaki, Masayuki</au><au>Izumi, Namiki</au><au>Yotsuyanagi, Hiroshi</au><au>Suzuki, Michihiro</au><au>Itoh, Fumio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of resistance‐associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J Med Virol</addtitle><date>2017-01</date><risdate>2017</risdate><volume>89</volume><issue>1</issue><spage>99</spage><epage>105</epage><pages>99-105</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><abstract>Sustained virological responses (SVR) by daclatasvir (DCV) and asunaprevir (ASV) therapy for genotype 1b hepatitis C virus (HCV) infected patients has been significantly affected by pre‐existence of Y93 H resistance‐associated variants (RAVs) in the non‐structural protein 5A (NS5A) region. The aim of this study was to elucidate the dominancy of naturally occurring RAVs in viral quasispecies on treatment outcomes in patients with HCV. In total, 138 patients were prospectively selected from 152 patients treated with DCV and ASV, where evaluation of treatment outcomes at 12 weeks post‐treatment was possible. Pre‐treatment RAVs in the non‐structural protein 3 and NS5A regions were detected by polymerase chain reaction (PCR)‐Invader assays, and the ratio of Y93H RAVs in viral quasispecies was measured by quantitative PCR‐Invader assay. Among 25 patients detected the Y93H RAV, the Y93H ratio was 1–25% in 5 patients, 26–75% in 7 patients, and ≥76% in 13 patients. Overall, SVR at 12 weeks after the completion of treatment (SVR12) was 91% (125/138), and those with Y93H ratios of <1%, 1–25%, 26–75%, and ≥76% were 99%, 100%, 71%, and 23%, respectively. Thus, the SVR12 decreased as the HCV Y93H ratio increased (P < 0.0001). The dominancy of pre‐treatment RAVs of DCV and ASV affected its treatment outcomes, suggesting that evaluating the dominancy of HCV RAVs could be required for every other direct‐acting antiviral agent treatments. J. Med. Virol. 89:99–105, 2017. © 2016 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27329864</pmid><doi>10.1002/jmv.24608</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antiviral Agents - therapeutic use asunaprevir Carbamates Clinical outcomes daclatasvir Drug Resistance, Viral Female Genotype Genotype & phenotype Genotyping Techniques HCV Hepacivirus - classification Hepacivirus - genetics Hepacivirus - isolation & purification Hepatitis Hepatitis C virus Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - virology Humans Imidazoles - therapeutic use Isoquinolines - therapeutic use Male Middle Aged Mutation, Missense Polymerase Chain Reaction Prospective Studies Pyrrolidines resistance‐associated variant Sulfonamides - therapeutic use Sustained Virologic Response sustained virological response Treatment Outcome Valine - analogs & derivatives Viral Nonstructural Proteins - genetics Virology |
| title | Impact of resistance‐associated variant dominancy on treatment in patients with HCV genotype 1b receiving daclatasvir/asunaprevir |
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