An Evaluation of IL-10 Encoded by Cytomegalovirus in the Prediction of Coronary Artery Disease in People Living with HIV

Cytomegalovirus (CMV) seropositivity associates with cardiovascular disease in healthy adults, but associations are unclear in people living with HIV (PLWH) despite their high CMV burden. However, CMV antibody levels correlated with inflammatory biomarkers only in PLWH who subsequently developed coronary artery disease (CAD), so the effects of CMV in an individual may vary. Here we investigate the role of CMV-encoded interleukin-10 (cmvIL-10) in PLWH on anti-retroviral therapy. Plasma levels of cmvIL-10 and antibodies reactive with a cmvIL-10 peptide or a lysate of CMV-infected fibroblasts were assessed in PLWH with or without CAD. cmvIL-10 was assessed at diagnosis/selection (T0) and 12 months earlier (T-12), with anti-cmvIL-10 also assessed at -24 and -36 months (n = 36-58/group). Plasma cmvIL-10 was recorded as positive in 5-10 PLWH per group, irrespective of CAD status. Of 21 PLWH with detectable cmvIL-10, only six were positive at both timepoints. Anti-cmvIL-10 was measurable in all samples, at levels independent of cmvIL-10, CAD or time of sampling. Amongst PLWH without CAD, the detection of cmvIL-10 associated with higher levels of CXCL10 (T0 and T-12) and lower levels of the IL-1 receptor antagonist (IL-1Ra; T0 only). At T-12, anti-cmvIL-10 correlated with IL-1Ra in PLWH without CAD (<i>p</i> = 0.01), and sCD14 in PLWH with CAD (<i>p</i> = 0.01). Anti-cmvIL-10 correlated with VCAM-1 at several timepoints in both groups. Hence, cmvIL-10 may be produced episodically, inducing anti-cmvIL-10 peptide antibody, which may represent levels of the cytokine averaged over time. Plasma levels of cmvIL-10 and anti-cmvIL-10 antibody associated differently with inflammatory biomarkers in PLWH with and without CAD, suggesting mechanisms by which host responses to CMV may have different clinical consequences.