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

Álvaro H. Borges, Jemma L. O'Connor, Andrew N. Phillips, James D. Neaton, Birgit Grund, Jacqueline Neuhaus, Michael J. Vjecha, Alexandra Calmy, Kersten K. Koelsch, Jens D. Lundgren

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalJournal of Infectious Diseases
Volume214
Issue number3
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (grants U01AI46957 and U01AI068641 to the ESPRIT and SMART and grants U01AI042170 and U01AI46362 to the SMART), the Research Council at Rigshospitalet, and the Danish National Research Foundation (grant DNRF126).

Publisher Copyright:
© 2016 The Author.

Keywords

  • D-dimer
  • HIV
  • IL-6
  • cancer
  • cardiovascular disease
  • hsCRP
  • inflammation

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