{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:48:45Z","timestamp":1780613325116,"version":"3.54.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Fifty-three participants (53\/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP &amp; ELF scores were 6.2 (IQR 4.6\u20137.8) kPa, 325 (IQR 279\u2013351) dB\/m and 9.1 (IQR 8.6\u20139.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target &gt;90%]; 83% (95%CI 70%-92%) participant retention [target &gt;65%]; 5.5% of data were missing [target &lt;20%]. There were noo Serious Adverse Reactions; mild-moderate intensity Adverse Reactions were reported by five participants (5\/23, 22% (95%CI 5%-49%)) [target &lt;10%]. All Adverse Reactions resolved. Secondary outcomes: no important differences were seen by treatment group for the change from baseline in LSM, CAP or ELF scores<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p><jats:bold>Clinical trial registry:<\/jats:bold> ISCRTN, registration number <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.isrctn.com\/31461655\" xlink:type=\"simple\">31461655<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0288598","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T17:35:59Z","timestamp":1689356159000},"page":"e0288598","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepmarc: A 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7186-2482","authenticated-orcid":true,"given":"Daniel","family":"Bradshaw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iga","family":"Abramowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Bremner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Gilleece","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Housman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Miras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Orkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashini","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Curnock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gompels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-1417","authenticated-orcid":true,"given":"Emily","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chadwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicky","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"issue":"6","key":"pone.0288598.ref001","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.jhep.2015.11.004","article-title":"EASL-EASD-EASO 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I. Conceptual framework and item selection","volume":"30","author":"JE Ware","year":"1992","journal-title":"Med Care."},{"issue":"5","key":"pone.0288598.ref030","first-page":"353","article-title":"The validity and reproducibility of a work productivity and activity impairment instrument.","volume":"4","author":"MC Reilly","year":"1993","journal-title":"PharmacoeconomicsEpub 1993"},{"key":"pone.0288598.ref031","author":"U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS","year":"2009","journal-title":"Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0."},{"key":"pone.0288598.ref032","first-page":"869","article-title":"A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus AIDS","volume":"30","author":"M Thompson","year":"2016"},{"issue":"3","key":"pone.0288598.ref033","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/liv.12896","article-title":"The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease","volume":"36","author":"KM Irvine","year":"2016","journal-title":"Liver international: official journal of the International Association for the Study of the Liver"},{"issue":"1","key":"pone.0288598.ref034","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/QAI.0b013e3182a7a97a","article-title":"Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients","volume":"65","author":"RM Gulick","year":"2014","journal-title":"Journal of acquired immune deficiency syndromes"},{"key":"pone.0288598.ref035","doi-asserted-by":"crossref","first-page":"i5239","DOI":"10.1136\/bmj.i5239","article-title":"CONSORT 2010 statement: extension to randomised pilot and feasibility trials","volume":"355","author":"SM Eldridge","year":"2016","journal-title":"BMJ"},{"key":"pone.0288598.ref036","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/biomet\/26.4.404","article-title":"The use of confidence or fiducial limits illustrated in the case of the binomial","volume":"26","author":"CJ Clopper","year":"1934","journal-title":"Biometrika"},{"key":"pone.0288598.ref037","volume-title":"An introduction to medical statistics","author":"M. Bland","year":"2015","edition":"4"},{"key":"pone.0288598.ref038","volume-title":"Stata Statistical Software: Release 17","author":"StataCorp. 2021.","year":"2021"},{"issue":"4","key":"pone.0288598.ref039","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jcv.2011.12.024","article-title":"Comparison of the rate and size of HIV-1 viral load blips with Roche COBAS TaqMan HIV-1 versions 1.0 and 2.0 and implications for patient management","volume":"53","author":"NJ Garrett","year":"2012","journal-title":"Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology"},{"key":"pone.0288598.ref040","author":"SL Pett","year":"2021"},{"key":"pone.0288598.ref041","author":"P Ingiliz","year":"2021"},{"issue":"8","key":"pone.0288598.ref042","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/infdis\/jiaa246","article-title":"Prevalence and Risk Factors of Moderate-to-Severe Hepatic Steatosis in Human Immunodeficiency Virus Infection: The Copenhagen Co-morbidity Liver Study","volume":"222","author":"DM Kirkegaard-Klitbo","year":"2020","journal-title":"The Journal of infectious diseases"},{"issue":"6","key":"pone.0288598.ref043","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/cid\/cix467","article-title":"Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus-Infected Patients With Nonalcoholic Fatty Liver Disease. 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