The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB-4 > 1.45), significant fibrosis (APRI > 1.5 or FIB-4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB-4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57-0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3-1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART-naïve HIV-positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis.
Bibliographical noteFunding Information:
Supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes Ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Supported by NIH Grants UM1-AI068641 and UM1-AI120197. Dr. Dharan has received support through an Australian Government Research Training Program Scholarship. The Kirby Institute is funded by the
Australian Government Department of Health and Ageing. The Burnet Institute receives funding from the Victorian Operational Infrastructure Support Program. Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health (award R01DA015999), Janssen-Cilag Pty Ltd and Gilead Sciences Inc as investigator-initiated studies. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Australian Government. Dr. Matthews is supported by an Australian National Health and Medical Research Council Fellowship. © 2018 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30296 Potential conflict of interest: Dr. Sarmento-Castro advises and is on the speakers bureau for MSD, Abbvie, and Gilead. Dr. Matthews received grants from Gilead and Abbvie. Dr. Rockstroh consults for Abbott, Abivax, Merck and ViiV. He consults and is on the speakers bureau for Gilead. Dr. Stephan advises for Abbvie, ViiV, Bristol Myers Squibb, Jannsen, Stada, and Astellas. He advises for and received grants from Gilead and MSD.
© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.