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Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive ART.

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Hsu DC, Ma YF, Hur S, Li D, Rupert A, Scherzer R, Kalapus SC, Deeks S, Sereti I, Hsue PY,


Hsu DC, Ma YF, Hur S, Li D, Rupert A, Scherzer R, Kalapus SC, Deeks S, Sereti I, Hsue PY, (click to view)

Hsu DC, Ma YF, Hur S, Li D, Rupert A, Scherzer R, Kalapus SC, Deeks S, Sereti I, Hsue PY,

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AIDS (London, England) 2016 5 12()

Abstract
OBJECTIVE
To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection.

DESIGN
Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy.

METHODS
Cryopreserved mononuclear cells and plasma were used to evaluate markers of T cell and monocyte activation, inflammation and coagulopathy. Carotid artery intima-media thickness (CIMT) was measured by high-resolution ultrasound at the common, bifurcation and internal carotid regions. Associations of immunologic markers with CIMT and all-cause mortality were assessed using multivariable linear regression and Cox proportional hazards regression.

RESULTS
The majority of participants were male (93%) and white (67%), median age of 48.5 years and median CD4 T cell count of 522 cells/μL. The median baseline IMT was 1.0 mm. Over a median of 8.3 years of follow-up, 12 deaths occurred.In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte CCR5 expression (5.4%, 95%CI [2.4-8.4], p = 0.001) was associated with greater common carotid IMT. Higher plasma IL-6 was associated with greater bifurcation (8.0%, 95%CI [2.3-13.7], p = 0.007) and overall mean IMT (5.2%, 95%CI [0.7-9.7], p = 0.026).Finally, higher plasma IL-6 (HR 1.9, 95%CI [1.0-3.7], p = 0.030), internal carotid (HR 4.1, 95%CI [1.2-13.7], p = 0.022) and mean IMT (HR 5.2, 95%CI [1.2-22.1], p = 0.026) were individually associated with all-cause mortality.

CONCLUSIONS
Higher monocyte CCR5 expression and plasma IL-6 were associated with atherosclerosis, independent of traditional cardiovascular risk factors. IL-6 and CIMT were individually associated with all-cause mortality. The impact of therapies targeting immune activation in CVD in treated HIV infection merits additional investigation.

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