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

Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive antiretroviral therapy.
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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) 30(13) 2065-74 doi 10.1097/QAD.0000000000001149

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 men (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-year follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte C-C motif chemokine receptor 5 (CCR5) expression [5.4%, P = 0.001] was associated with greater common CIMT. Higher plasma IL-6 was associated with greater bifurcation [8.0%, P = 0.007] and overall mean IMT [5.2%, P = 0.026]. Finally, higher plasma IL-6 [hazard ratio 1.9, P = 0.030], internal carotid [hazard ratio 4.1, P = 0.022] and mean IMT [hazard ratio 5.2, P = 0.026] were individually associated with all-cause mortality.

CONCLUSION
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 cardiovascular disease in treated HIV infection merits additional investigation.

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