| Publication Abstract Display | | Type: Published Abstract | | Title: Association of subclinical CMV DNA and immunologic markers of cardiovascular disease. | | Authors: Garg A, Gianella S, Nakazawa M, Spector S | | Year: | | Publication: CROI 2018 | | Volume: Issue: Pages: | | Abstract:HIV-CMV co-infected persons are at increased risk of cardiovascular disease (CVD) associated with persistent inflammation. Persons with high interferon (IFN)- response to CMV have increased numbers of endothelium homing receptor (CX3CR1)-expressing cells that are associated with CVD. Here, we investigated the effect of subclinical CMV replication on these markers.
80 paired PBMC samples were collected from 40 CMV-seropositive, early HIV-infected men starting ART within a median of 3 mo from estimated date of infection, and achieved suppressed HIV RNA within a median of 3 mo on ART. PBMC were obtained 12 mo apart (1st sample a median of 34 wks post-ART initiation). IFN response to CMV was determined by ELISPOT using a peptide pool of CMVpp65 antigen; CMV specific memory T cells were identified by flow cytometry. CMV and EBV levels were measured by ddPCR. Data were analyzed using a mixed effects regression model to predict associations between CMV shedding, IFN production and CX3CR1-expressing CD4+ and CD8+ T cells over time. Bayesian hierarchical models were used to quantify individual differences in CMV and EBV replication over time. Participants were classified as low (LR)- or high-responders (HR) according to IFN production (< or >100 SFU/106 cells).
26 (65%) participants were classified as HR and 14 (35%) as LR at the 1st time-point which did not change over time nor was influenced by CMV levels (median SFU/106 cells at 1st/2nd time-point: HR: 383/308 vs LR: 21/41). Change in IFN levels over time was influenced by CMV levels (p<0.01), as individuals with a greater decline in IFN had increased levels of CMV DNA, compared to those with low CMV. Higher CMV was also associated with increased numbers of CD28+CD27-CD4+ T cells expressing CX3CR1 (p<0.001). Similarly, increased IFN production was associated with increased numbers of CMV-specific CX3CR1+CD28+CD27-CD4+ and CD8+ T cells (P<0.001). Using a similar interaction model, EBV was not associated with any of these findings (P>0.2).
These findings demonstrate in HIV-CMV co-infected persons on suppressive ART that higher CMV levels and IFN responses are associated with a subset of CMV-specific memory T cells expressing CX3CR1, and that high and low IFN responders maintain their response category over time. Thus, we have identified a subgroup of HIV-infected CMV IFN HR with increased numbers of circulating T cells expressing CX3CR1 who may be at increased risk of CVD and other inflammatory diseases. |
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