Cause-specific mortality in HIV-positive patients who survived ten years after starting antiretroviral therapy

• Type of Material: Article
• Authors: Adam Trickey, University of Bristol; Margaret T. May, University of Bristol; Janne Vehreschild, German Centre for Infection Research; Niels Obel, Copenhagen University Hospital; Michael John Gill, University of Calgary; Heidi Crane, University of Washington; Christoph Boesecke, Universität Bonn; Hasina Samji, British Columbia Centre for Excellence in HIV-AIDS; Sophie Grabar, Interactions Arbres/Micro-organismes (IaM); Charles Cazanave, Groupe Hospitalier Pellegrin; Matthias Cavassini, Centre Hospitalier Universitaire Vaudois; Leah Shepherd, University College London; Antonella d'Arminio Monforte, Università degli Studi di Milano; Colette Smit, Stichting HIV Monitoring; Michael Saag, University of Alabama; Fiona Lampe, University College London; Vicky Hernando, Centro Nacional de Epidemiologia; Marta Montero, Hospital Universitari i Politècnic La Fe; Robert Zangerle, Medizinische Universitat Innsbruck; Amy C. Justice, Yale University; Timothy Sterling, Vanderbilt University; Jose Miro, University of Barcelona; Suzanne Ingle, University of Bristol; Jonathan A. C. Sterne, University of Bristol; Jodie L. Guest, Emory University
• Language: English
• Date: 2016-08-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Trickey et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0160460
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 8
• Start Page: e0160460
• End Page: e0160460
• Grant/Funding Information: Sources of funding of individual cohorts include the Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the French, Italian and Spanish Ministries of Health, the Swiss National Science Foundation (grant 33CS30_134277), the Ministry of Science and Innovation and the “Spanish Network for AIDS Research (RIS; ISCIII-RETIC RD06/006), the Stichting HIV Monitoring, the European Commission (EuroCoord grant 260694), the British Columbia and Alberta Governments, the National Institutes of Health (NIH) [UW Center for AIDS Research (CFAR) (NIH grant P30 AI027757), UAB CFAR (NIH grant P30 AI027767), The Vanderbilt-Meharry CFAR (NIH grant P30 AI54999), National Institute on Alcohol Abuse and Alcoholism (U10-AA13566, U24-AA020794), the US Department of Veterans Affairs, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the VHA Office of Research and Development and unrestricted grants from Abbott, Gilead, Tibotec-Upjohn, ViiV Healthcare, MSD, GlaxoSmithKline, Pfizer, Bristol Myers Squibb, Roche and Boehringer-Ingelheim.; COHERE receives funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement n° 260694.; Jonathan Sterne is funded by National Institute for Health Research Senior Investigator award NF-SI-0611-10168.; The Danish HIV Cohort Study is founded by Preben and Anne Simonsens Foundation. Data from 11 European cohorts were pooled in June 2014 within COHERE in EuroCoord (www.cohere.org and www.EuroCoord.net).; This work was supported by the UK Medical Research Council (MRC) MR/J002380/1—http://www.mrc.ac.uk/—and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union.
• Keywords: Middle Aged; Female; Young Adult; Adult; Male; Demography; Humans; Survival Analysis; Risk Factors; Anti-HIV Agents; Aged; Adolescent; HIV-1; HIV Infections
• Research Categories: Health Sciences, Public Health; Health Sciences, Epidemiology

Abstract

Objectives: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. Methods: We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results: During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liverrelated disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions: Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. Copyright: