Abstract Body

Background: Chronic HIV-1 infection is characterized by systemic immune activation and inflammation and may contribute to cardiovascular disease (CVD) risk. We assessed relationships of monocyte [MO] subsets, CD38+HLA-DR+CD8+ T cells and various cytokines, to HIV immune dysregulation and carotid intima-media thickness (cIMT).

Methods: We conducted a longitudinal analysis from a cohort study of CVD risk in HIV-infected subjects aged > 40 years on stable antiretroviral therapy (ART) > 6 months. Fasting blood was assessed for glucose, insulin and lipids. Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry for MO subsets [classical MO (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14low/+CD16++)] and CD38+HLA-DR+ CD8+ T cells at baseline. Plasma biomarker multiplexing was performed. Soluble biomarkers included sE-selectin, sVCAM-1, sICAM-1, MMP-9, MPO, tPA-1, CRP, SAA, SAP, IL-1β, IL-6, IL-8, IL-10, TNF-α, MCP-1, VEGF, IFN-γ, and NT ProBNP. High resolution B-mode ultrasound images of the right carotid bifurcation were obtained at baseline and year 2. Changes in cIMT were assessed. Pearson correlation and linear regression were used for statistical analysis.

Results: We studied 50 subjects: 84% male, median age 49 (Q1,Q3: 46, 56) years, median CD4 count 461 (317,578) cells/mm3, with HIV RNA<50 copies/ml in 84%. Change in cIMT correlated positively with log values of non-classical MO count (r=0.37, p=0.020) and percentage (r=0.36, p=0.025), MCP-1 (r=0.42, p=0.0024) and TNF-a (r=0.30, p=0.036). Non-classical MO percentage correlated with MCP-1 (r=0.32, p=0.045). Among the monocyte subsets, only non-classical MO predicted cIMT at the bifurcation independent of age, BMI, smoking, CD4 percent and presence of HIV RNA (β=0.13, p=0.040). Additionally, if study subjects were split by the non-classical MO percentage median value (7.33%) to High and Low levels, then the baseline cIMT value itself tended to predict the cIMT change at year 2 at the High level (R2=19.6%), but not at Low level of non-classical MO (R2=0.2%).

Conclusions: HIV immune dysregulation is associated with elevated levels of non-classical MO. Increased non-classical MO subsets parallel increases in pro-inflammatory cytokines such as MCP-1. Non-classical MO predict progression of cIMT at the bifurcation in HIV-infected individuals on suppressive ART independent of traditional cardiometabolic and HIV immunovirologic factors, and may contribute to CVD.