Immune reconstitution inflammatory syndrome (IRIS)

Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response to a variety of pathogens in response to antiretroviral therapy-mediated recovery of the immune system in HIV-infected patients

• IRIS is an exaggerated inflammatory immune response that kills up to one-third of affected people (1)
  
  
• up to 54% of patients develop hyperinflammatory reactions known as immune reconstitution inflammatory syndrome (IRIS) within the first month of antiretroviral therapy (ART) initiation (2)
  
  
  • cryptococcal meningitis (CM), an infection around the brain that is caused by the fungus Cryptococcus neoformans (1)
    • CM-IRIS may be the result of an unbalanced recovery of the immune system leading to an inappropriate immune response to persisting C. neoformans fragments and proteins that are slowly cleared from the body over months
      
      
  • tuberculosis (TB) is the second most common IRIS-associated disease in unselected studies of patients starting ART, accounting for 20% of reported IRIS cases overall, and is the commonest in resource-limited settings (2,3)
    • TB-associated IRIS may present in two ways:
      • 'paradoxical' worsening of symptoms of known disease, either at a new body site or at the original body site, with an incidence of 8-43% of TB-co-infected individuals starting ART;
      • or 'unmasking' of occult Mycobacterium tuberculosis infection, in which infection was not clinically apparent prior to ART but presents floridly during ART, affecting around 5% among those starting ART without known TB infection in South Africa
  • the immunopathogenesis remains poorly understood, but clinical and pathological observations suggest that the mechanisms of IRIS vary according to the target antigen

Reference:

• Boulware DR et al. Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study. PLoS Med. 2010 Dec; 7(12): e1000384
• Narendran G. et al. Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV patients with culture confirmed pulmonary tuberculosis in India and the potential role of IL-6 in prediction. PLoS One. 2013 May 17;8(5):e63541.
• Haddow L et al. Circulating inflammatory biomarkers can predict and characterize tuberculosis-associated immune reconstitution inflammatory syndrome.AIDS: June , 2011; 25(9): 1163-1174