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Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection

Borges, AH; O'Connor, JL; Phillips, AN; Neaton, JD; Grund, B; Neuhaus, J; Vjecha, MJ; ... Lundgren, JD; + view all (2016) Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection. The Journal of Infectious Diseases , 214 (3) pp. 408-416. 10.1093/infdis/jiw173. Green open access

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Abstract

BACKGROUND: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation. METHODS: Participants receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non–AIDS-related death, AIDS, cardiovascular disease (CVD), and non–AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log2-transformed IL-6, hsCRP, and D-dimer levels were calculated using Cox models. Marginal models modelling multiple events tested for equal effects of biomarker levels on different end points. RESULTS: Among 4304 participants, there were 157 all-cause deaths, 117 non–AIDS-related deaths, 101 AIDS cases, 121 CVD cases, and 99 non–AIDS-defining malignancies. IL-6 was more strongly associated with most end points, compared with hsCRP. IL-6 appeared to be a stronger predictor than D-dimer for CVD and non–AIDS-defining malignancies, but 95% CIs overlapped. Independent associations of IL-6 were stronger for non–AIDS-related death (HR, 1.71; 95% CI, 1.43–2.04) and all-cause death (HR, 1.56; 95% CI, 1.33–1.84) and similar for CVD (HR, 1.35; 95% CI, 1.12–1.62) and non–AIDS-defining malignancies (HR, 1.30; 95% CI, 1.06–1.61). There was heterogeneity of IL-6 (P < .001) but not hsCRP (P = .15) or D-dimer (P = .20) as a predictor for different end points. CONCLUSIONS: IL-6 is a stronger predictor of fatal events than of CVD and non–AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals.

Type: Article
Title: Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/infdis/jiw173
Publisher version: http://dx.doi.org/10.1093/infdis/jiw173
Language: English
Additional information: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. This is a pre-copyedited, author-produced PDF of an article accepted for publication in The Journal of Infectious Diseases following peer review. The version of record Borges, AH; O'Connor, JL; Phillips, AN; Neaton, JD; Grund, B; Neuhaus, J; Vjecha, MJ; (2016) Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection. The Journal of Infectious Diseases , 214 (3) pp. 408-416. 10.1093/infdis/jiw173 is available online at: http://dx.doi.org/10.1093/infdis/jiw173
Keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, HIV, inflammation, IL-6, hsCRP, D-dimer, cardiovascular disease, cancer, INCIDENT CARDIOVASCULAR-DISEASE, ANTIRETROVIRAL THERAPY ART, CORONARY-HEART-DISEASE, T-CELL-ACTIVATION, MENDELIAN RANDOMIZATION, COAGULATION BIOMARKERS, INFLAMMATORY MARKERS, RISK, CANCER, DEATH
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/1490437
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