Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients

J Infect. 2017 May;74(5):456-465. doi: 10.1016/j.jinf.2017.01.016. Epub 2017 Feb 9.


Objectives: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.

Methods: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time.

Results: At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)).

Conclusions: None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients.

Keywords: Anti-tuberculosis treatment; Biomarkers; Cambodia; HIV/tuberculosis co-infection; IL-1 receptor antagonist; TB-IRIS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use*
  • Biomarkers / blood*
  • Case-Control Studies
  • Female
  • HIV Infections / complications*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome* / blood
  • Immune Reconstitution Inflammatory Syndrome* / complications
  • Immune Reconstitution Inflammatory Syndrome* / diagnosis
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Male
  • Randomized Controlled Trials as Topic
  • Tuberculosis* / blood
  • Tuberculosis* / complications
  • Tuberculosis* / diagnosis
  • Tuberculosis* / drug therapy


  • Antitubercular Agents
  • Biomarkers
  • Interleukin 1 Receptor Antagonist Protein