Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus
Current treatment of chronic hepatitis C virus (HCV) infection is based on the combination of pegylated interferon‐α and ribavirin. The recent development of direct‐acting antiviral (DAA) molecules that are active on HCV, together with in vitro and in vivo studies showing that these drugs may lead t...
Gespeichert in:
| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2011-05, Vol.53 (5), p.1742-1751 |
|---|---|
| 1. Verfasser: | |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1751 |
|---|---|
| container_issue | 5 |
| container_start_page | 1742 |
| container_title | Hepatology (Baltimore, Md.) |
| container_volume | 53 |
| creator | Pawlotsky, Jean‐Michel |
| description | Current treatment of chronic hepatitis C virus (HCV) infection is based on the combination of pegylated interferon‐α and ribavirin. The recent development of direct‐acting antiviral (DAA) molecules that are active on HCV, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on DAAs. A new standard‐of‐care treatment will soon be available for both treatment‐naive and treatment‐experienced patients infected with HCV genotype 1, based on a triple combination of pegylated interferon‐α, ribavirin, and a protease inhibitor (either telaprevir or boceprevir). With this therapy, most failures to eradicate infection in treatment‐adherent patients are due to an inadequate response to pegylated interferon‐α and ribavirin, in the context of a low genetic barrier to resistance of first‐generation protease inhibitors. This article reviews patterns of resistance to HCV DAA drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon‐α and ribavirin, the consequences of treatment failure, and possible means of optimizing future therapies that use DAAs. (HEPATOLOGY 2011;) |
| doi_str_mv | 10.1002/hep.24262 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_863768205</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>863768205</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4502-59bf0341ec3514762965fde38f971888a124604df60c79711036ca82fbf1b95e3</originalsourceid><addsrcrecordid>eNp90c1qVDEYBuBQKnZsXfQGSqCIujhtvvxnKUO1QsEu6jpkcpJpypkzY5Jj6c5L8Bq9ElNntCDoKpA8fD95EToGcgaE0PPbsDmjnEq6h2YgqOoYE2QfzQhVpDPAzAF6UcodIcRwqp-jAwpMcWlghuxNDq6uwlhxdGmYcsBu7HEOJZXqRh_wfaq3uE85-Prj23fnaxqXzdT0NWU34D5Py4Ld0qWxVNwmcTXVVPAct_epHKFn0Q0lvNydh-jz-4ub-WV39enDx_m7q85zQWgnzCISxiF4JoArSY0UsQ9MR6NAa-2Ackl4HyXxql0BYdI7TeMiwsKIwA7R623dTV5_mUKpdpWKD8PgxrCeitWSKakpEU2--a8EpaQUIJhu9PQveree8tj2aEq2co_DNvV2q3xel5JDtJucVi4_WCD2MR_bfsX-yqfZk13FabEK_R_5O5AGXu2AK94NMbcMUnlyHCRow5o737r7NISHf3e0lxfX29Y_ASWBphE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1766823514</pqid></control><display><type>article</type><title>Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Pawlotsky, Jean‐Michel</creator><creatorcontrib>Pawlotsky, Jean‐Michel</creatorcontrib><description>Current treatment of chronic hepatitis C virus (HCV) infection is based on the combination of pegylated interferon‐α and ribavirin. The recent development of direct‐acting antiviral (DAA) molecules that are active on HCV, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on DAAs. A new standard‐of‐care treatment will soon be available for both treatment‐naive and treatment‐experienced patients infected with HCV genotype 1, based on a triple combination of pegylated interferon‐α, ribavirin, and a protease inhibitor (either telaprevir or boceprevir). With this therapy, most failures to eradicate infection in treatment‐adherent patients are due to an inadequate response to pegylated interferon‐α and ribavirin, in the context of a low genetic barrier to resistance of first‐generation protease inhibitors. This article reviews patterns of resistance to HCV DAA drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon‐α and ribavirin, the consequences of treatment failure, and possible means of optimizing future therapies that use DAAs. (HEPATOLOGY 2011;)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.24262</identifier><identifier>PMID: 21374691</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; Drug Resistance, Viral ; Drug Therapy, Combination ; Drugs ; Failure ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepacivirus - drug effects ; Hepatitis ; Hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - drug therapy ; Hepatology ; HIV ; Human immunodeficiency virus ; Humans ; Interferon ; Interferon-alpha - therapeutic use ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Pharmacology. Drug treatments ; Polyethylene Glycols - therapeutic use ; Protease Inhibitors - therapeutic use ; Recombinant Proteins ; Ribavirin - therapeutic use ; Treatment Failure</subject><ispartof>Hepatology (Baltimore, Md.), 2011-05, Vol.53 (5), p.1742-1751</ispartof><rights>Copyright © 2011 American Association for the Study of Liver Diseases</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4502-59bf0341ec3514762965fde38f971888a124604df60c79711036ca82fbf1b95e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.24262$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.24262$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24161893$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21374691$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pawlotsky, Jean‐Michel</creatorcontrib><title>Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Current treatment of chronic hepatitis C virus (HCV) infection is based on the combination of pegylated interferon‐α and ribavirin. The recent development of direct‐acting antiviral (DAA) molecules that are active on HCV, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on DAAs. A new standard‐of‐care treatment will soon be available for both treatment‐naive and treatment‐experienced patients infected with HCV genotype 1, based on a triple combination of pegylated interferon‐α, ribavirin, and a protease inhibitor (either telaprevir or boceprevir). With this therapy, most failures to eradicate infection in treatment‐adherent patients are due to an inadequate response to pegylated interferon‐α and ribavirin, in the context of a low genetic barrier to resistance of first‐generation protease inhibitors. This article reviews patterns of resistance to HCV DAA drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon‐α and ribavirin, the consequences of treatment failure, and possible means of optimizing future therapies that use DAAs. (HEPATOLOGY 2011;)</description><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Drug Resistance, Viral</subject><subject>Drug Therapy, Combination</subject><subject>Drugs</subject><subject>Failure</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepacivirus - drug effects</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatology</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Interferon</subject><subject>Interferon-alpha - therapeutic use</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Protease Inhibitors - therapeutic use</subject><subject>Recombinant Proteins</subject><subject>Ribavirin - therapeutic use</subject><subject>Treatment Failure</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c1qVDEYBuBQKnZsXfQGSqCIujhtvvxnKUO1QsEu6jpkcpJpypkzY5Jj6c5L8Bq9ElNntCDoKpA8fD95EToGcgaE0PPbsDmjnEq6h2YgqOoYE2QfzQhVpDPAzAF6UcodIcRwqp-jAwpMcWlghuxNDq6uwlhxdGmYcsBu7HEOJZXqRh_wfaq3uE85-Prj23fnaxqXzdT0NWU34D5Py4Ld0qWxVNwmcTXVVPAct_epHKFn0Q0lvNydh-jz-4ub-WV39enDx_m7q85zQWgnzCISxiF4JoArSY0UsQ9MR6NAa-2Ackl4HyXxql0BYdI7TeMiwsKIwA7R623dTV5_mUKpdpWKD8PgxrCeitWSKakpEU2--a8EpaQUIJhu9PQveree8tj2aEq2co_DNvV2q3xel5JDtJucVi4_WCD2MR_bfsX-yqfZk13FabEK_R_5O5AGXu2AK94NMbcMUnlyHCRow5o737r7NISHf3e0lxfX29Y_ASWBphE</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Pawlotsky, Jean‐Michel</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wolters Kluwer Health, Inc</general><scope>IQODW</scope><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>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201105</creationdate><title>Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus</title><author>Pawlotsky, Jean‐Michel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4502-59bf0341ec3514762965fde38f971888a124604df60c79711036ca82fbf1b95e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Drug Resistance, Viral</topic><topic>Drug Therapy, Combination</topic><topic>Drugs</topic><topic>Failure</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepacivirus - drug effects</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatology</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Interferon</topic><topic>Interferon-alpha - therapeutic use</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyethylene Glycols - therapeutic use</topic><topic>Protease Inhibitors - therapeutic use</topic><topic>Recombinant Proteins</topic><topic>Ribavirin - therapeutic use</topic><topic>Treatment Failure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pawlotsky, Jean‐Michel</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pawlotsky, Jean‐Michel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2011-05</date><risdate>2011</risdate><volume>53</volume><issue>5</issue><spage>1742</spage><epage>1751</epage><pages>1742-1751</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Current treatment of chronic hepatitis C virus (HCV) infection is based on the combination of pegylated interferon‐α and ribavirin. The recent development of direct‐acting antiviral (DAA) molecules that are active on HCV, together with in vitro and in vivo studies showing that these drugs may lead to the selection of resistant viruses if administered alone, has raised concerns that resistance may undermine therapy based on DAAs. A new standard‐of‐care treatment will soon be available for both treatment‐naive and treatment‐experienced patients infected with HCV genotype 1, based on a triple combination of pegylated interferon‐α, ribavirin, and a protease inhibitor (either telaprevir or boceprevir). With this therapy, most failures to eradicate infection in treatment‐adherent patients are due to an inadequate response to pegylated interferon‐α and ribavirin, in the context of a low genetic barrier to resistance of first‐generation protease inhibitors. This article reviews patterns of resistance to HCV DAA drugs in development, the mechanisms underlying treatment failure when these drugs are combined with pegylated interferon‐α and ribavirin, the consequences of treatment failure, and possible means of optimizing future therapies that use DAAs. (HEPATOLOGY 2011;)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21374691</pmid><doi>10.1002/hep.24262</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0270-9139 |
| ispartof | Hepatology (Baltimore, Md.), 2011-05, Vol.53 (5), p.1742-1751 |
| issn | 0270-9139 1527-3350 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_863768205 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Biological and medical sciences Drug Resistance, Viral Drug Therapy, Combination Drugs Failure Gastroenterology. Liver. Pancreas. Abdomen Hepacivirus - drug effects Hepatitis Hepatitis C Hepatitis C virus Hepatitis C, Chronic - drug therapy Hepatology HIV Human immunodeficiency virus Humans Interferon Interferon-alpha - therapeutic use Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Pharmacology. Drug treatments Polyethylene Glycols - therapeutic use Protease Inhibitors - therapeutic use Recombinant Proteins Ribavirin - therapeutic use Treatment Failure |
| title | Treatment failure and resistance with direct‐acting antiviral drugs against hepatitis C virus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T15%3A59%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Treatment%20failure%20and%20resistance%20with%20direct%E2%80%90acting%20antiviral%20drugs%20against%20hepatitis%20C%20virus&rft.jtitle=Hepatology%20(Baltimore,%20Md.)&rft.au=Pawlotsky,%20Jean%E2%80%90Michel&rft.date=2011-05&rft.volume=53&rft.issue=5&rft.spage=1742&rft.epage=1751&rft.pages=1742-1751&rft.issn=0270-9139&rft.eissn=1527-3350&rft.coden=HPTLD9&rft_id=info:doi/10.1002/hep.24262&rft_dat=%3Cproquest_cross%3E863768205%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1766823514&rft_id=info:pmid/21374691&rfr_iscdi=true |