Immune Reconstitution Inflammatory Syndrome (IRIS)



  • Immune Reconstitution Inflammatory Syndrome (IRIS) is an Inflammatory Response with Either Paradoxical Worsening of a Preexisting Infection (“Paradoxical IRIS”) or Worsening of an Unrecognized Preexisting Infection (“Unmasking IRIS”)
    • Treatment of HIV/AIDS with Antiretroviral Therapy (ART) is the Best Described Precipitant of IRIS


Immune Reconstitution Due to Human Immunodeficiency Virus (HIV) Treatment (see Human Immunodeficiency Virus)

AIDS-Defining Illnesses Associated with Immune Reconstitution Inflammatory Syndrome (IRIS)

Clinical Data

  • Systematic Review and Meta-Analysis of IRIS (Lancet Infect Dis, 2010) [MEDLINE]
    • Incidence of IRIS is Variable Across Different AIDS-Defining Illnesses
    • Incidence of IRIS is Inversely Correlated with the CD4 Count at Baseline
      • Higher Incidence of IRIS is Observed in Patients with CD4 <50 cells/μL: particularly in patients with tuberculosis, CMV-associated immune recovery uveitis, and cryptococcal meningitis
      • Higher Incidence of IRIS at Lower CD4 Counts is Not Surprising, Since CMV Retinitis is Typically an Infection Which Occurs at CD4 <50 cells/μL, Cryptococcal Meningitis Typically Occurs at Low CD4 Counts (While Tuberculosis and Kaposi Sarcoma Tend to Occur at Higher CD4 Counts)
    • Mortality Rate Associated with IRIS: 4%
      • Mortality Rate from IRIS is Much Higher with Cryptococcal Meningitis

Immune Reconstitution in Other Clinical Scenarios

  • Treatment of Lepromatous Leprosy (see Leprosy)
    • Epidemiology: cases of IRIS have been described in non-HIV patients treated for leprosy (Rev Infect Dis, 1981) [MEDLINE]
  • Treatment of Tuberculosis (see Tuberculosis)
    • Epidemiology: cases of IRIS have been described in non-HIV patients treated for tuberculosis (Lancet, 1984) [MEDLINE]
  • Engraftment of Hematopoietic Stem Cell Transplant (HSCT) (see Hematopoietic Stem Cell Transplant)
  • Recovery of Neutropenia After Chemotherapy
  • Withdrawal of Anti-Tumor Necrosis Factor-α (TNFα) Therapy (see Anti-Tumor Necrosis Factor-α Therapy)
    • Epidemiology: cases have been described in non-HIV patients with withdrawal of anti-TNFα therapy (Diagn Microbiol Infect Dis, 2009) [MEDLINE]
  • Withdrawal of Corticosteroids (see Corticosteroids)
    • Epidemiology: cases have been described in non-HIV patients with corticosteroid withdrawal
  • Withdrawal of Immunosuppression in Transplant Patients with Cryptococcosis
    • Epidemiology: cases have been reported (Clin Infect Dis, 2005) [MEDLINE]

Clinical Manifestations

General Comments

IRIS Associated with Preexisting Cryptococcal Infection

IRIS Associated with Cytomegalovirus (CMV)

IRIS Associated with Mycobacterial Infection

IRIS Associated with Hepatitis B/C

IRIS Associated with JC Virus

IRIS Associated with Leishmaniasis

IRIS Associated with Pneumocystis Jirovecii

IRIS Associated with Varicella-Zoster Virus (VZV)

IRIS Associated with Sarcoidosis


Delayed Initiation of HIV Therapy