Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 214, Issue 3, Pages 408-416Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw173
Keywords
HIV; inflammation; IL-6; hsCRP; D-dimer; cardiovascular disease; cancer
Categories
Funding
- National Institutes of Health [U01AI46957, U01AI068641, U01AI042170, U01AI46362]
- Research Council at Rigshospitalet
- Danish National Research Foundation [DNRF126]
- Medical Research Council [MC_UU_12023/23] Funding Source: researchfish
Ask authors/readers for more resources
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 log(2)-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available