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Background <p>Tuberculosis (TB) remains the most common opportunistic infection among people living with HIV (PLWH). Dysregulated cytokine responses during HIV/TB co-infection may contribute to immune dysfunction and disease progression. However, the longitudinal dynamics of cytokine profiles and their associations with clinical indicators during treatment remain incompletely understood.</p> Methods <p>In this prospective exploratory longitudinal study, we enrolled 24 patients with HIV/TB co-infection, 24 patients with HIV monoinfection, and 24 healthy controls. Serum concentrations of seven cytokines, including IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ, as well as routine clinical indicators, were measured at baseline and on days 7, 14, 21, 30, 60, 90, and 180 after treatment initiation. Longitudinal changes were analyzed using linear mixed-effects models, and associations between cytokines and clinical indicators were assessed using exploratory Spearman’s rank correlation analysis.</p> Results <p>At baseline, patients with HIV/TB co-infection showed evidence of immune and inflammatory alterations, with higher NEUT, NEUT%, and AST levels and lower LYM, LYM%, and ALB levels than both comparison groups (FDR-adjusted <i>P</i> &lt; 0.05). During follow-up, IL-6 and IL-2 peaked on days 7 and 60, respectively, whereas IFN-γ, TNF-α, and IL-17 peaked on day 21 and subsequently declined. IL-4 and IL-10 peaked on days 60 and 21, respectively, and decreased to levels comparable to those in healthy controls by days 180 and 90, respectively. Exploratory correlation analyses showed time-dependent changes in the associations between cytokines and clinical indicators. The correlations of TNF-α with NEUT and IFN-γ with CD4⁺ T cells and LYM shifted from negative to positive, whereas the correlation between IL-17 and CD8⁺ T cells shifted from positive to negative.</p> Conclusion <p>Patients with HIV/TB co-infection showed stage-specific changes in cytokine profiles and clinical indicators during combined antiretroviral and anti-tuberculosis therapy. Cytokine levels and their associations with clinical indicators changed dynamically and gradually approached a relatively stable state over time. These findings suggest that immune and inflammatory status may evolve during treatment, although further studies are needed to validate these exploratory observations.</p>

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From inflammatory to reconstitution: a longitudinal exploratory study of cytokine dynamics in HIV/TB co-infected patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月20日

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  • Zengjie Qian,
  • Jianjian Li,
  • Cuixian Yang,
  • Mi Zhang,
  • Xia Li,
  • Junyi Zhao,
  • Mei Yang,
  • Hengli Liu,
  • Youwang Lu,
  • Hongli Fan

摘要

Background

Tuberculosis (TB) remains the most common opportunistic infection among people living with HIV (PLWH). Dysregulated cytokine responses during HIV/TB co-infection may contribute to immune dysfunction and disease progression. However, the longitudinal dynamics of cytokine profiles and their associations with clinical indicators during treatment remain incompletely understood.

Methods

In this prospective exploratory longitudinal study, we enrolled 24 patients with HIV/TB co-infection, 24 patients with HIV monoinfection, and 24 healthy controls. Serum concentrations of seven cytokines, including IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ, as well as routine clinical indicators, were measured at baseline and on days 7, 14, 21, 30, 60, 90, and 180 after treatment initiation. Longitudinal changes were analyzed using linear mixed-effects models, and associations between cytokines and clinical indicators were assessed using exploratory Spearman’s rank correlation analysis.

Results

At baseline, patients with HIV/TB co-infection showed evidence of immune and inflammatory alterations, with higher NEUT, NEUT%, and AST levels and lower LYM, LYM%, and ALB levels than both comparison groups (FDR-adjusted P < 0.05). During follow-up, IL-6 and IL-2 peaked on days 7 and 60, respectively, whereas IFN-γ, TNF-α, and IL-17 peaked on day 21 and subsequently declined. IL-4 and IL-10 peaked on days 60 and 21, respectively, and decreased to levels comparable to those in healthy controls by days 180 and 90, respectively. Exploratory correlation analyses showed time-dependent changes in the associations between cytokines and clinical indicators. The correlations of TNF-α with NEUT and IFN-γ with CD4⁺ T cells and LYM shifted from negative to positive, whereas the correlation between IL-17 and CD8⁺ T cells shifted from positive to negative.

Conclusion

Patients with HIV/TB co-infection showed stage-specific changes in cytokine profiles and clinical indicators during combined antiretroviral and anti-tuberculosis therapy. Cytokine levels and their associations with clinical indicators changed dynamically and gradually approached a relatively stable state over time. These findings suggest that immune and inflammatory status may evolve during treatment, although further studies are needed to validate these exploratory observations.