Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals

Objectives The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART). Methods Baseline mean common carotid artery (CCA) intima-media thickness (IMT) and carotid plaque (IMT>1.5cm) were evaluated in the first 60 subjects enrolled in the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial. All subjects were adults on stable ART with evidence of heightened T-cell activation (CD8+CD38+HLA-DR+19%) or increased inflammation (high-sensitivity C-reactive protein 2mg/L). All had fasting low-density lipoprotein (LDL) cholesterol 130mg/dL. Results Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/L, respectively. All had HIV-1 RNA<400 HIV-1 RNA copies/mL. Mean CCA-IMT was correlated with log-transformed CD8+CD38+HLA-DR+ percentage (r=0.326; P=0.043), and concentrations of interleukin-6 (r=0.283; P=0.028), soluble vascular cell adhesion molecule (sVCAM; r=0.434; P=0.004), tumour necrosis factor- receptor-I (TNFR-I; r=0.591; P<0.0001) and fibrinogen (r=0.257; P=0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P=0.007) and fibrinogen (P=0.033) remained significant. Subjects with plaque (n=22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P=0.002], and had a higher CD8+CD38+HLA-DR+ percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P=0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P=0.008] compared with those without plaque. Pro-inflammatory monocyte subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque. Conclusions Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol.