Background: Chronic inflammation contributes to premature cardiovascular disease (CVD) among HIV⁺ patients. Identifying immunologic mechanisms that may accelerate HIV-related atherogenesis will help identify new treatment strategies.

Methods: We evaluated coronary artery calcium (CAC) progression in a prospective HIV cohort enrolled from 2004 to 2006 (the SUN Study). We abstracted clinical data and measured CAC by computed tomography scans at enrollment and 2 years later. We defined 2-year progression, using a validated approach, as either: incident (change from undetectable to detectable), or significant increase (difference ≥2.5 on square root scale). We characterized cellular immunophenotypes by multi-color flow cytometry of baseline cryopreserved peripheral blood mononucular cells (Table) and identified predictors of CAC progression by logistic regression after adjusting for traditional and HIV-related risk factors.

Results: Baseline characteristics for participants with baseline and 2-year CAC assessments (n = 436) were:

median age 42 years, 78% male, 59% non-Hispanic white, 41% smokers, 20% taking antihypertensive therapy, 9% diabetic, median total cholesterol 180 mg/dL, median CD4 count 481cells/mm³, 78% receiving HAART, 72% plasma HIV RNA level <400 copies/mL, and 82% (n = 356) no detectable CAC. At 2 years, 12.6% (n = 55) had CAC progression; 6.4% (n = 28) with incident CAC and 6.2% (n = 27) with significantly increased CAC. Factors associated with CAC progression included: older age, male gender, antihypertensive therapy, lipid-lowering therapy, and a higher Framingham risk score (p <0.05 for all). The table presents associations between baseline frequencies of immunophenotypes and CAC progression adjusted for traditional and HIV-related risk factors. Higher frequencies of activated monocytes (CD14⁺/CD16⁺ or CD14^var/CD16⁺) were independently associated with greater likelihood of CAC progression, but tissue factor expression, and T cell activation and senescence phenotypes were not.

Conclusions: Monocyte activation was independently associated with greater CAC progression in this contemporary HIV cohort. In contrast to T cell activation that has been classically associated with AIDS-related disease progression, these data highlight the consequences of persistent activation of innate immunity for HIV-related CVD risk and emphasize the need for treatments directed at monocyte activation.