The Relationship Between Monocyte Activation Markers And Atherosclerosis In HIV/AIDS Patients

[Purpose]:To compare the difference of ABI and PWV between ARV naive HIV-infected subjects and HIV negative controls. To investigate the association between the markers of monocyte activation and atherosclerosis in HIV-infected patients and explore the possible risk factors of atherosclerosis in HIV-infected individuals. To compare the difference of status of atherosclerosis between HAART-treated patients and ARV naive HIV-infected subjects.[Methods]:We enrolled40HIV-infected patients without receiving HAART and20age and gender ratio matched HIV negative controls. We used non-invasive parameters pulse wave velocity (PWV) and ankle brachial index (ABI) to evaluate the function of the arterial wall as an indicator of atherosclerotic vascular damage and compared the difference of ABI and PWV between two groups. Using flow-cytometry,we differentiated monocytes into CD14++CD16-and CD16+cells, which we further subdivided into CD14++CD16+and CD14dim CD16+cells. CD14++CD16+monocyte percentage and CD16+monocyte percentage are regarded as markers of monocyte activation. We determined CD14++CD16+monocyte and CD16+monocyte percentage and compared the difference of these monocyte activation markers between two groups. Neopterin is produced by activated monocyte/macrophages on stimulation with interferon-y released from T lymphocytes and is an activation marker for monocyte/macrophages. Using ELISA-based assays, we measured plasms neopterin concentrations and compared the difference between both groups. We divided all the subjects into group with arterial stiffness and group without arterial stiffness based on PWV value. We compared CD14++CD16+monocyte percentage, CD16+monocyte percentage and plams neopterin concentraion between the group with arterial stiffness and group without arterial stiffness and explored the role of chronic monocyte activation induced by HIV in atherosclerosis.In addtion, to compare the status of atherosclerotic vascular damage between HAART treated patients (patients who had received HAART for more than12months were defined as HAART treated patients)and ART naive subjects, we assessed ABI and PWV in both groups.[Results]:A lower ABI and a higher PWV were found in ART naive HIV-infected subjects conpared with age and gender ratio matched HIV negative controls. The percentage of artery stiffness was significantly higher in ART naive HIV-infected patients. Comparing with HIV negative controls,the monocyte activation markers CD14++CD16+monocyte percentage, CD16+monocyte percentage and plasms neoperin concentration were significantly higher in ART-naive HIV-infected subjects. The monocyte activation marker CD14++CD16+monocyte percentage was corrletaed with T lymphocyte activation marker the ratio of CD8+CD38+/CD8+and the plasma neoperin concentration was found to be correlated with CD14++CD16+monocyte percentage. We divided all the subjects into group with artery stiffness and group without artery stiffness based on PWV value. Older age, HIV infection, the level of hsCRP and the percentage of CD16+monocyte were correlated with arterial stiffness. Comparing with HAART-naive subjects, HAART treated patients had significantly higher PWV. The percentage of diabetes and the level of glucose and triglyceride were also significantly higher in HAART treated patients.[Conclusions]:(1) Comparing with HIV-uninfected subjects, ARV naive HIV-infected individuals are at increased risk of atherosclerosis and cardiovascular events.(2) Chronic immune activation induced by HIV will increase the level of monocyte activation, inducing the increase of the CD14++CD16+monocyte percentage,CD16+monocyte percentage and plasms neoperin concentration.(3) In HIV-infected subjects, monocyte activation marker CD14++CD16+monocyte percentage is correlated with T lymphocyte activation marker the ratio of CD8+CD38+/CD8+and plasma neoperin concentration is found to be correlated with CD14++CD16+monocyte percentage.(4)HIV infection, older age, high level of HsCRP and CD16+monocyte percentage are correlated with artery stiffness and increased risk of atherosclerosis and cardiovascular events. Our result reveals a signicant association between CD16+monocytes and hsCRP with atherosclerosis in HIV-infected subjects with low cardiovascular risks, suggesting that chronic immune activation and inflammation may contribute to atherosclerosis in HIV-infected individuals.(5) HAART-treated patients were likely to have further increased risk of atherosclerosis and cardiovascular events, partly attributed to side effects of HAART on long terms such as high level of glucose and triglyceride.