Association of Cytomegalovirus DNA and Immunologic Markers of Cardiovascular Disease

Background. Persons living with human immunodeficiency virus (HIV) (PLWH) with high cytomegalovirus (CMV)-specific interferon (IFN) gamma response have increased numbers of endothelium homing receptor (CX3CR1)(+)-expressing cells that are associated with cardiovascular disease. The current study was performed to investigate the effect of cellular levels of CMV DNA on these markers. Methods. Eighty paired peripheral blood mononuclear cell samples were collected >= 12 months apart from 40 CMV-seropositive PLWH with suppressed HIV RNA, who started antiretroviral therapy at median of 3-months of infection. The samples were assessed for CMV-specific IFN-gamma response by means of enzyme-linked immunospot assay, and participants were classified as low responders (LRs) or high responders (HRs) based on IFN-gamma production (<= 100 or >100 spot-forming units [SFUs]/10(5) cells). Results. Of the 40 participants, 26 (65%) were HRs and 14 (35%) LRs at baseline, which did not change over time or by CMV levels (median at first/second time points, 383/308 SFUs/10(6) cells for HRs vs 21/41 SFUs/10(6) for LRs). A decrease in IFN-gamma over time was associated with higher CMV DNA levels (P < .01). High CMV response was also associated with increased CD28(+)CD27(-)CD4(+) T cells expressing CX3CR1 (P < .001). Similarly, increased IFN-gamma production was associated with increased CMV-specific CX3CR1(+)CD28(+)CD27(-)CD4(+) and CD8(+) T cells (P < .001). Conclusions. These findings demonstrate that levels of CMV-specific IFN-gamma response in PLWH are stable over time, and that HRs have increased circulating T cells expressing CX3CR1 that may put them at increased risk of cardiovascular disease and other inflammatory diseases.