Diagnostic Implications of MCP-1, IL-18, IL-6 and Comorbidities in Persons with HIV on ART

Background/Objectives: Despite good viremia control with antiretroviral therapy (ART), there is persistent inflammation in persons with HIV (PWH). Among HIV individuals, data on comparative analysis of inflammatory cytokine levels based on presence or absence of non-infectious comorbid diseases (NCDs) is still limited. The assessment of systemic markers of inflammation also requires appropriate sample selection and processing. We hypothesized that serum and plasma inflammatory cytokines are differentially regulated by interplay of ART and comorbidities in PWH. The objectives of this pilot study were to compare serum and plasma levels of inflammatory cytokines in PWH on ART and determine whether differential levels of serum and plasma inflammatory markers are modulated by interplay of ART and NCDs. Method: Clinical and demographic data, as well as paired serum and plasma samples were obtained from 14 participants. Multiplex immunoassay was used to assess immune mediators in both serum and plasma, and clinical data was compared with absolute values of immune mediators. Results: Nine out of 14 PWH presented with one or more NCDs (+NCDs), with hypertension being the most prevalent at 100%. There was no significant difference between mean levels of paired plasma and serum levels of IL-6, and TNF-α, but serum levels of MCP-1, IL-18 and IL-8 were significantly higher in plasma relative to serum (p=0.000002, 0.05 and 0.000005 respectively). MCP-1 levels were comparatively high relative to other analytes, followed by IL-18, but these were independent of NCD. IL-6 expression, though low compared to MCP-1 and IL-18, was significantly higher in both plasma and serum of PWH with NCDs, especially those with hypertension and psychiatric conditions (p=0.0495 and 0.02 respectively). There was no significant difference between mean levels of paired plasma and serum levels of IL-6, IL-18 and TNF-α, but serum levels of MCP-1, IL-18 and IL-8 were significantly higher in plasma relative to serum (p=0.000002, 0.05 and 0.000005 respectively). Conclusion: Selection of serum or plasma for assessment of inflammation is dependent on the cytokine of interest. MCP-1 and IL-18 are possible predictors of HIV infection, while IL-6 level is a possible predictor of comorbidity in PWH on ART irrespective of blood analyte.