Immunologic predictors of coronary artery calcium progression in a contemporary HIV cohort

Abstract

Background: Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies.

Methods: Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors.

Results: Baseline characteristics for the analysis cohort (n=436) were median age 42 years, median CD4 cell count 481 cells/μl, and 78% receiving antiretroviral therapy. Higher frequencies of CD16 monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14/CD16 (P=0.02), 1.36 for CD14/CD16 (P=0.06), and 1.69 for CD14/CD16 (P=0.01)]. Associations for CD16 monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers.

Conclusion: Circulating CD16 monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.

Figure 1. Monocyte Phenotype by CAC Outcome

After gating on live cells that express HLA-DR and lack expression of markers of T, B, and NK cells (CD2, CD3, CD19, CD20, and CD56), the proportions of monocytes expressing CD14 (horizontal axis) and CD16 (vertical axis) are shown for representative patients with: A) No CAC: absent at baseline and at year 2 follow up, B) Incident CAC: absent at baseline but detectable at year 2 follow up, C) Stable CAC: detectable at baseline but without significant increase over 2 years of follow up, and D) Increased CAC: detectable at baseline with a significant increase over 2 years of follow up. The percent of cells for each quadrant are reported in the outer most corner. Greater frequencies of CD14+/CD16+ (upper right quadrant) and CD14^var/CD16+ (both upper quadrants combined) are seen with subsequent CAC progression (‘B’ and ‘D’).