The tuberculosis-associated immune reconstitution inflammatory syndrome: recent advances in clinical and pathogenesis research. Issue 6 (November 2018)

• Record Type: Journal Article
• Authors: Walker, Naomi F.; Stek, Cari; Wasserman, Sean; Wilkinson, Robert J.; Meintjes, Graeme
• Is Part Of: Current opinion in HIV & AIDS. Volume 13:Issue 6(2018:Nov.)
• Publication Date: 2018-11
• Subjects: HIV-1 infection -- immune reconstitution inflammatory syndrome -- paradoxical -- tuberculosis -- unmasking; AIDS (Disease) -- Periodicals; HIV infections -- Periodicals; HIV Infections -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; Infections à VIH -- Périodiques; Sida -- Périodiques; AIDS (Disease); HIV infections; Periodicals; 616.9792005
• DOI: 10.1097/COH.0000000000000502
• Languages: English
• ISSNs: 1746-630X

Abstract

Abstract : 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/μl 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/μl 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.