{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T12:04:47Z","timestamp":1776513887751,"version":"3.51.2"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.16594.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000}}],"reference-count":27,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K01532X\/1"],"award-info":[{"award-number":["MR\/K01532X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12023\/22"],"award-info":[{"award-number":["MC_UU_12023\/22"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["14\/02\/17"],"award-info":[{"award-number":["14\/02\/17"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["206296, 090532\/Z\/09\/Z"],"award-info":[{"award-number":["206296, 090532\/Z\/09\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:\u00a0<\/ns3:bold>\n                    The World Health Organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:\u00a0<\/ns3:bold>\n                    A total of\n                    <ns3:bold\/>\n                    202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1\/2). Participants not cured following first-line treatment were retreated with 12 weeks\u2019 sofosbuvir\/ledipasvir\/ribavirin. The primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:\u00a0<\/ns3:bold>\n                    All evaluable participants achieved SVR12 overall (197\/197, 100% [95% CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95% CI -3.8%, +3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91% [86%-97%] (92\/101) for fixed-duration vs 48% [39%-57%] (47\/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23\/32)) than VUS1 (36% [25%-48%] (24\/66)). Overall, first-line SVR12 was 72% [65%-78%] (70\/101) without ribavirin and 68% [61%-76%] (69\/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3\/26)) than without (38% [21%-58%] (11\/29), p=0.01).\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:\u00a0<\/ns3:bold>\n                    Unsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir\/ledipasvir\/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly\u00a0reduced resistance emergence in those failing first-line therapy.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>ISRCTN Registration<\/ns3:bold>\n                    : 37915093 (11\/04\/2016).\n                  <\/ns3:p>","DOI":"10.12688\/wellcomeopenres.16594.2","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T07:16:44Z","timestamp":1627543004000},"page":"93","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6475-5056","authenticated-orcid":false,"given":"Graham 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Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T06:28:05Z","timestamp":1628749685000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":27,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.16594.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.18848.r45219","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.18848.r45220","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.18848.r45219","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.18848.r45220","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.18848.r45220, Kittiyod Poovorawan, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand, 03 Aug 2021, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2#referee-response-45220","order":0,"name":"referee-response-45220","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.18848.r45219, George Lau, The Humanity & Health Medical Centre, Hong Kong, Hong Kong, 12 Aug 2021, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/6-93\/v2#referee-response-45219","order":1,"name":"referee-response-45219","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [206296]. STOP-HCV-1 was funded by the National Institutes of Health Research\u2019s Efficacy Mechanism Evaluation programme (Project number 14\/02\/17). Virological analysis was supported by MRC Stratified Medicine Consortium (MR\/K01532X\/1 \u2013 STOP-HCV Consortium) and core funding to the Wellcome Trust Centre for Human Genetics provided by the Wellcome Trust (090532\/Z\/09\/Z). The MRC Clinical Trials Unit at UCL is supported by funding from the MRC (MC_UU_12023\/22). ASW is an NIHR Senior Investigator. GC is supported in part by the BRC of Imperial College NHS Trust and is an NIHR Research Professor. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}