The tuberculosis-associated immune reconstitution inflammatory syndrome: recent advances in clinical and pathogenesis...

Antiretroviral therapy (ART) is an essential, life-saving intervention for HIV infection. However, ART initiation is frequently complicated by the tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in TB endemic settings. Here, we summarize the current understanding highlighting the recent evidence.

The incidence of paradoxical TB-IRIS is estimated at 18% (95% CI 16-21%), higher than previously reported and may be over 50% in high-risk groups. Early ART initiation in TB patients increases TB-IRIS risk by greater than two-fold, but is critical in TB patients with CD4 counts less than 50 cells/microl because it improves survival. There remains no validated diagnostic test for TB-IRIS, and biomarkers recently proposed are not routinely used. Prednisone initiated alongside ART in selected patients with CD4 less than 100 cells/microl reduced the risk of paradoxical TB-IRIS by 30% in a recent randomized-controlled trial (RCT) and was not associated with significant adverse effects. Effective also for treating paradoxical TB-IRIS, corticosteroids remain the only therapeutic intervention for TB-IRIS supported by RCT trial data. TB-IRIS pathogenesis studies implicate high antigen burden, innate immune cell cytotoxicity, inflammasome activation and dysregulated matrix metalloproteinases in the development of the condition.

Specific biomarkers would aid in identifying high-risk patients for interventions and a diagnostic test is needed. Clinicians should consider prednisone for TB-IRIS prevention in selected patients. Future research should focus on improving diagnosis and investigating novel therapeutic interventions, especially for patients in whom corticosteroid therapy is contraindicated.