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

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.