{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:51:27Z","timestamp":1791478287824,"version":"4.3.4"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI068634"],"award-info":[{"award-number":["AI068634"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI068636"],"award-info":[{"award-number":["AI068636"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI106701"],"award-info":[{"award-number":["AI106701"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals is an open-label, 2-cohort, Phase 1 clinical trial in which the second cohort assessed the safety and efficacy of 8 weeks of ledipasvir\/sofosbuvir for the treatment of acute HCV infections in participants with chronic human immunodeficiency virus (HIV)-1 infections. This final analysis of the second cohort had a planned accrual of 27 participants, based on non-inferiority criteria, compared to the study-defined, historical, sustained virologic response (SVR) of 60% with pegylated-interferon\/ribavirin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled 27 men (9 Hispanic; 11 White, non-Hispanic; 5 Black, non-Hispanic; 2 Asian or Pacific Islander; median age 46 years). Most (96%) had HCV genotype-1 infection and 59% had the favorable interleukin 28B CC genotype. The median baseline HCV RNA load was 6.17 log10 IU\/mL (interquartile range 4.51 \u2013 6.55). All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment (90% confidence interval 90\u2013100%), achieving non-inferiority versus the 60% historic benchmark. No treatment discontinuations occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This multicenter clinical trial, investigating 8 weeks of ledipasvir\/sofosbuvir for acute HCV infections in men with HIV infections, reports a 100% SVR. This study provides the rationale for larger studies of shortened courses of direct-acting antiviral therapies in persons with HIV infections, including those with high baseline HCV RNA loads.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trials Registration<\/jats:title><jats:p>NCT02128217.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciy913","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T20:07:53Z","timestamp":1542053273000},"page":"514-522","source":"Crossref","is-referenced-by-count":26,"title":["Ledipasvir\/Sofosbuvir for 8 Weeks to Treat Acute Hepatitis C Virus Infections in Men With Human Immunodeficiency Virus Infections: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals"],"prefix":"10.1093","volume":"69","author":[{"given":"Susanna","family":"Naggie","sequence":"first","affiliation":[{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Fierer","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Hughes","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Y","family":"Kim","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Luetkemeyer","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Vu","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhoanna","family":"Roa","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Rwema","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M","family":"Brainard","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc, Foster City, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G","family":"McHutchison","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc, Foster City, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion G","family":"Peters","sequence":"additional","affiliation":[{"name":"University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J","family":"Kiser","sequence":"additional","affiliation":[{"name":"University of Colorado, Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M","family":"Marks","sequence":"additional","affiliation":[{"name":"Weill Cornell, New York City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T","family":"Chung","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Acquired Immunodeficiency Syndrome Clinical Trials Group (ACTG) A5327 Study Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Alston-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Weichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thucuma","family":"Sise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Cosimano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswald","family":"Dadson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Luetkemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Dwyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Grenade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Stroberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Ilmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Henn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi","family":"Kiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Sbrolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Nuffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wyles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"McGregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tondria","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Tebas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Bedimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto C","family":"Arduino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristoteles","family":"Villamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2019091012042297700_CIT0001","author":"Global Hepatitis Report 2017","year":"2017"},{"key":"2019091012042297700_CIT0002","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1053\/j.gastro.2009.02.006","article-title":"Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men","volume":"136","author":"van de Laar","year":"2009","journal-title":"Gastroenterology"},{"key":"2019091012042297700_CIT0003","first-page":"453","article-title":"Increases in hepatitis C virus infection related to injection drug use among persons aged \u226430 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012","volume":"64","author":"Zibbell","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2019091012042297700_CIT0004","author":"EASL Recommendations on Treatment of Hepatitis C 2016","year":"2016","journal-title":"J Hepatol"},{"key":"2019091012042297700_CIT0005","unstructured":"American Association for the Study of Liver Disease, Infectious Diseases Society of America . Recommendations for testing, managing, and treating hepatitis C. Available at: http:\/\/www.hcvguidelines.org\/"},{"key":"2019091012042297700_CIT0006","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S1473-3099(16)30408-X","article-title":"Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study","volume":"17","author":"Deterding","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2019091012042297700_CIT0007","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S2468-1253(17)30003-1","article-title":"Ledipasvir-sofosbuvir for 6 weeks to treat acute hepatitis C virus genotype 1 or 4 infection in patients with HIV coinfection: an open-label, single-arm trial","volume":"2","author":"Rockstroh","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2019091012042297700_CIT0008","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/cid\/cix025","article-title":"Sofosbuvir plus ribavirin without interferon for treatment of acute hepatitis C virus infection in HIV-1-infected individuals: SWIFT-C","volume":"64","author":"Naggie","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2019091012042297700_CIT0009","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1080\/15284336.2017.1280594","article-title":"Sofosbuvir in the treatment of early HCV infection in HIV-infected men","volume":"18","author":"El Sayed","year":"2017","journal-title":"HIV Clin Trials"},{"key":"2019091012042297700_CIT0010","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1002\/hep.28844","article-title":"Sofosbuvir and ribavirin for 6 weeks is not effective among people with recent hepatitis C virus infection: The DARE-C II study","volume":"64","author":"Martinello","year":"2016","journal-title":"Hepatology"},{"key":"2019091012042297700_CIT0011","volume-title":"Gilead Sciences","author":"Gilead Sciences. Harvoni U.S. prescribing information","year":"2015"},{"key":"2019091012042297700_CIT0012","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1056\/NEJMoa1501315","article-title":"Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1","volume":"373","author":"Naggie","year":"2015","journal-title":"N Engl J Med"},{"key":"2019091012042297700_CIT0013","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/135965350601100817","article-title":"Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals","volume":"11","author":"Vogel","year":"2006","journal-title":"Antivir Ther"},{"key":"2019091012042297700_CIT0014","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/QAD.0b013e328343443b","volume":"25","author":"Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference","year":"2011","journal-title":"Aids"},{"key":"2019091012042297700_CIT0015","author":"US Department of Health and Human Services, N.I.o.H., National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse dvents"},{"key":"2019091012042297700_CIT0016","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1086\/596770","article-title":"Characteristics and treatment outcomes among HIV-infected individuals in the Australian trial in acute hepatitis C","volume":"48","author":"Matthews","year":"2009","journal-title":"Clin Infect Dis"},{"key":"2019091012042297700_CIT0017","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2893.2009.01167.x","article-title":"Early treatment improves outcomes in acute hepatitis C virus infection: a meta-analysis","volume":"17","author":"Corey","year":"2010","journal-title":"J Viral Hepat"},{"key":"2019091012042297700_CIT0018","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1473-3099(13)70059-8","article-title":"Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial","volume":"13","author":"Deterding","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"2019091012042297700_CIT0019","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.virol.2014.12.033","article-title":"T cell exhaustion during persistent viral infections","volume":"479-480","author":"Kahan","year":"2015","journal-title":"Virology"},{"key":"2019091012042297700_CIT0020","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.immuni.2017.09.006","article-title":"Early transcriptional divergence marks virus-specific primary human CD8+ T cells in chronic versus acute infection","volume":"47","author":"Wolski","year":"2017","journal-title":"Immunity"},{"key":"2019091012042297700_CIT0021","article-title":"The DAHHS 2 Study: 8 weeks of grazoprevir plus elbasvir for acute hepatitis C virus genotype 1 or 4 infection.","volume-title":"25th Conference on Retroviruses and Opportunistic Infections","author":"Boerekamps"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/69\/3\/514\/29022294\/ciy913.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T21:18:58Z","timestamp":1662412738000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/69\/3\/514\/5421820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,28]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3,28]]},"published-print":{"date-parts":[[2019,7,18]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciy913","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8,1]]},"published":{"date-parts":[[2019,3,28]]}}}