{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:05:57Z","timestamp":1760853957167,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T00:00:00Z","timestamp":1514419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K01AI110181","R00AI120851"],"award-info":[{"award-number":["K01AI110181","R00AI120851"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["K24DA034621"],"award-info":[{"award-number":["K24DA034621"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Summary<\/jats:title>Treatment with the direct\u2010acting antiviral agent (DAA<\/jats:styled-content>) sofosbuvir (SOF<\/jats:styled-content>), an NS<\/jats:styled-content>5B inhibitor, and velpatasvir (VEL<\/jats:styled-content>), an NS<\/jats:styled-content>5A inhibitor, demonstrates viral cure rates of \u226595% in hepatitis C virus (HCV<\/jats:styled-content>) genotypes (GT<\/jats:styled-content>) 1\u20106. Here, we investigated intrapatient HCV<\/jats:styled-content> diversity in NS<\/jats:styled-content>5A and NS<\/jats:styled-content>5B using Shannon entropy to examine the relationship between viral diversity and treatment outcome. At baseline, HCV<\/jats:styled-content> diversity was lowest in patients infected with HCV GT<\/jats:styled-content>3 as compared to the other GT<\/jats:styled-content>s, and viral diversity was greater in NS<\/jats:styled-content>5A than NS<\/jats:styled-content>5B (P<\/jats:italic>\u00a0<\u00a0.0001). Treatment outcome with SOF<\/jats:styled-content>\/VEL<\/jats:styled-content> or the comparator regimen of SOF<\/jats:styled-content> with ribavirin (RBV<\/jats:styled-content>) was not correlated with baseline diversity. However, among persons treated with SOF<\/jats:styled-content>\/VEL<\/jats:styled-content>, a decrease in diversity from baseline was observed at relapse in the majority virologic failures, consistent with a viral bottleneck event at relapse. In contrast, an increase in diversity was observed in 27% of SOF<\/jats:styled-content>+RBV<\/jats:styled-content> virologic failures. We investigated whether the increase in diversity was due to an increase in the transition rate, one mode of potential RBV<\/jats:styled-content>\u2010mediated mutagenesis; however, we found no evidence of this mechanism. Overall, we did not observe that viral diversity at baseline influenced treatment outcome, but the diversity changes observed at relapse can improve our understanding of RBV<\/jats:styled-content> viral suppression in vivo.<\/jats:p>","DOI":"10.1111\/jvh.12825","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T14:06:53Z","timestamp":1510063613000},"page":"344-353","source":"Crossref","is-referenced-by-count":2,"title":["Intrapatient viral diversity and treatment outcome in patients with genotype 3a hepatitis C virus infection on sofosbuvir\u2010containing regimens"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-0921","authenticated-orcid":false,"given":"N.","family":"Bhardwaj","sequence":"first","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Ragonnet\u2010Cronin","sequence":"additional","affiliation":[{"name":"University of California San Diego San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Murrell","sequence":"additional","affiliation":[{"name":"University of California San Diego San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Chodavarapu","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Martin","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Chang","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. J.","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-6352","authenticated-orcid":false,"given":"M.","family":"Sulkowski","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9633-8019","authenticated-orcid":false,"given":"A.","family":"Mangia","sequence":"additional","affiliation":[{"name":"Casa Sollievo della Sofferenza Hospital San Giovanni Rotondo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. O.","family":"Wertheim","sequence":"additional","affiliation":[{"name":"University of California San Diego San Diego CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Osinusi","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"McNally","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Brainard","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Mo","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. S.","family":"Svarovskaia","sequence":"additional","affiliation":[{"name":"Clinical Virology Gilead Sciences Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26744"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70216-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13027"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512612"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214853"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316366"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402454"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512610"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11531990-000000000-00000"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0b013e3181960819"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03153"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.12.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S55864"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100349200"},{"key":"e_1_2_8_17_1","first-page":"218","article-title":"Mechanism of action of ribavirin in the treatment of chronic hepatitis C","volume":"3","author":"Te HS","year":"2007","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04082"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-001-0308-0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2125"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.03.022"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i36.4808"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt768"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08309"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i12.1617"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti079"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002507"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu400"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msv035"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/v7092857"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vew024"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986706778773059"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-402"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2008.00980.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840380413"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3046"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00201-09"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.035"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.12.005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1177\/135965350300800603","article-title":"The potentiating effect of ribavirin on interferon in the treatment of hepatitis C: lack of evidence for ribavirin\u2010induced viral mutagenesis","volume":"8","author":"Schinkel J","year":"2003","journal-title":"Antivir Ther"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2893.2001.00265.x"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12825","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12825","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T08:02:43Z","timestamp":1695542563000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,28]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1111\/jvh.12825"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12825","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"type":"print","value":"1352-0504"},{"type":"electronic","value":"1365-2893"}],"subject":[],"published":{"date-parts":[[2017,12,28]]}}}