Interleukin-6 and Interferon-gamma Ratio as a Predictor of Immune State and Viral Suppression in HIV-1 Infection

Abstract

<title>Abstract</title> Introduction: Cytokine dysregulation is a key feature of HIV-1 infection with plasma Interleukin 6 (IL-6) largely observed to enhance HIV-1 replication whereas Interferon gamma (IFN-γ) inhibits it. Notably, IL-6 inhibits IFN-γ secretion through the STAT3 pathway to support HIV-1 survival. High IL-6: IFN-γ ratios may thus be linked to HIV-1 persistence. Although these cytokines are often evaluated separately, we assessed IL-6: IFN-γ ratio as a predictor of HIV-1 immune state and viral suppression. Methodology: A cross-sectional study was conducted with 240 people living with HIV on Antiretroviral Therapy (ART). Assessments included viral load, CD4 T-cell counts, IL-6, and IFN-γ, followed by the calculation of IL-6: IFN-γ ratios. Participants were categorized into viral suppressing (&lt; 1000 copies) and non-suppressing (&gt; 1000 copies) groups, as well as severe immune suppression (&lt; 200 CD4 T-cells) and non-severe (&gt; 200 CD4 T-cells). Correlations among HIV-1 viral load, CD4 counts, and cytokine levels were analyzed, and Welch’s T-test was used for comparisons. Results No significant correlations were found between HIV-1 viral load, CD4 counts, and the cytokine levels or ratios. However, IL-6 and IL-6: IFN-γ ratios were higher in viral suppressing patients (p = 0.024 and p = 0.017, respectively), while IFN-γ levels did not vary significantly. Among patients on ART for six months, IL-6 was elevated in viral non-suppressing individuals (p = 0.005). The classification accuracy of IL-6, IFN-γ, and their ratio varied, identifying 59%, 41%, and 65% of patients as viral suppressing or non-suppressing. Conclusion The IL-6: IFN-γ ratio enhances the classification accuracy of individuals living with HIV-1 compared to independent tests, though it is not a direct replacement for viral load or CD4 counts. Understanding IL-6 secretion patterns and their impact on IFN-γ may require a comprehensive cytokine profile and comparison with ART-naïve HIV-1 infected individuals.