To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection.
Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy.
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.
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.
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.