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Benefit of early versus deferred antiretroviral therapy on progression of liver fibrosis among people with HIV in the START randomized trial

Dharan, NJ; Neuhaus, J; Rockstroh, JK; Peters, L; Gordin, F; Arenas-Pinto, A; Emerson, C; ... INSIGHT START Study Group, ; + view all (2018) Benefit of early versus deferred antiretroviral therapy on progression of liver fibrosis among people with HIV in the START randomized trial. Hepatology 10.1002/hep.30296. (In press). Green open access

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Abstract

BACKGROUND: The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with HIV is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment trial (START) 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 antiretroviral therapy (ART) on liver fibrosis progression. DESIGN AND INTERVENTION: 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 enrolment (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. RESULTS: Of the 4684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4580 participants (2273 immediate treatment; 2307 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, 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. This article is protected by copyright. All rights reserved.

Type: Article
Title: Benefit of early versus deferred antiretroviral therapy on progression of liver fibrosis among people with HIV in the START randomized trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hep.30296
Publisher version: https://doi.org/10.1002/hep.30296
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: APRI, FIB-4, liver disease, non-invasive markers
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10061685
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