Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation

• Type of Material: Article
• Authors: April C Pettit, Vanderbilt University; Mark J Giganti, Vanderbilt University; Suzanne M Ingle, University of Bristol; Margaret T May, University of Bristol; Bryan E Shepherd, Vanderbilt University; Michael J Gill, University of Calgary; Gerd Fatkenheuer, University of Cologne; Sophie Abgrall, University of Paris 06; Michael S Saag, University of Alabama; Julia Del Amo, Carlos III Health Institute; Amy C Justice, Yale University; Jose M Miro, University of Barcelona; Matthias Cavasinni, Lausanne University Hospital; Francois Dabis, Bordeaux University Hospital; Antonella D Monforte, University of Milan; Peter Reiss, University of Amsterdam; Jodie L. Guest, Emory University; David Moore, British Columbia Centre for Excellence in HIV/AIDS; Leah Shepherd, University College London; Niels Obel, Copenhagen University Hospital
• Language: English
• Date: 2018-01-01
• Publisher: Wiley Open Access
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/jia2.25031
• Title of Journal or Parent Work: Journal of the International AIDS Society
• ISSN: 1758-2652
• Volume: 21
• Issue: 1
• Start Page: e25031
• End Page: e25031
• Grant/Funding Information: COHERE receives funding from the European Union Seventh Framework Programme (FP7/2007‐2013) under EuroCoord grant agreement no 260694.; Jose M. Miró received a personal intensification research grant #INT15/00168 during 2016 from Instituto de Salud Carlos III, Madrid, Spain.; Sources of funding for April Pettit: National Institutes of Health K08 AI104352.; Vanderbilt University Medical Center: Vanderbilt‐Meharry CFAR (NIH P30 AI 54999), Tennessee CFAR (NIH P30 AI110527), Sterling K24 (NIH K 24 AI065298).; Jonathan Sterne is funded by National Institute for Health Research Senior Investigator award NF‐SI‐0611‐10168.; PISCIS was supported in part by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Madrid (Spain), and Spanish Network for AIDS Research (RIS; ISCIII‐RETIC RD06/006).; The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, the Netherlands; and the Augustinus Foundation, Denmark.; This work was jointly funded by the UK Medical Research Council (MRC) (grant number MR/J002380/1) 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: Science & Technology; non-AIDS mortality; POPULATION-BASED COHORT; marginal structural model; RISK-FACTORS; MYOCARDIAL-INFARCTION; non-Hodgkin's lymphoma; DEATH; COLLABORATION ART-CC; Infectious Diseases; LIFE EXPECTANCY; Immunology; UNINFECTED INDIVIDUALS; Pneumocystis jiroveci pneumonia; tuberculosis; Life Sciences & Biomedicine; AIDS-defining events; HIV-INFECTED PATIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; IMPACT
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Introduction: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. Methods: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. Results: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). Conclusions: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.