4.2 Review

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

Journal

CURRENT OPINION IN HIV AND AIDS
Volume 13, Issue 6, Pages 512-521

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0000000000000502

Keywords

HIV-1 infection; immune reconstitution inflammatory syndrome; paradoxical; tuberculosis; unmasking

Funding

  1. National Institute for Health Research Academic Clinical Lecturership
  2. British Infection Association
  3. Academy of Medical Sciences UK
  4. Wellcome
  5. Medical Research Council UK
  6. British Heart Foundation
  7. Arthritis Research UK
  8. Royal College of Physicians and Diabetes UK
  9. EDCTP [TMA 2015 CDF-1018]
  10. Wellcome [203135/Z/16/Z, 10218, 104503, 203135, 098316]
  11. UKRI [10218]
  12. CRUK [10218]
  13. NIH [U01A1115940]
  14. South African Research Chairs Initiative of the Department of Science and Technology
  15. National Research Foundation (NRF) of South Africa [64787]
  16. NRF [UID: 85858]
  17. South African Medical Research Council
  18. National Department of Health [SAMRC-RFA-CC: TB/HIV/AIDS-01-2014]
  19. MRC [MC_U117588499] Funding Source: UKRI
  20. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI115940] Funding Source: NIH RePORTER

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Purpose of review 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. Recent findings 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/ml 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/ml 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. Summary 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.

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