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Immune Reconstitution Inflammatory Syndrome (IRIS)

Hannah Angle


  • An inflammatory syndrome divided into paradoxical and unmasking IRIS.
    • Unmasking IRIS refers to the flare-up of an underlying, preexisting infection in patients with HIV after antiretroviral therapy (ART) initiation
    • Paradoxical IRIS refers to the worsening of a previously treated Infection after Initiation of ART.
  • Typically develops between 1 week to a couple months after starting ART
  • Patients with lower CD4 counts and higher viral loads who respond well to ART are at higher risk of IRIS


  • IRIS is a clinical diagnosis
    • Presentation consistent with either a systemic or localized inflammatory response (specific clinical features dependent on underlying infection)
    • Most often seen in patients with significantly decreased CD4 counts who have a profound virologic and immunologic response to ART
    • Infections most associated with IRIS include meningeal presentations of Mycobacterium tuberculosis and Cryptococcus neoformans.
    • Other Infections include CMV, PJP, HSV, HBV, HHV-8, and Mycobacterium avium complex (MAC)
    • Need to rule out drug-resistant infection or nonadherence to antimicrobials, bacterial superinfection, or medication adverse effect


  • Prior to ART initiation, must evaluate for all opportunistic infections (OI), especially when an inflammatory response could cause swelling in an enclosed space (cryptococcal meningitis/encephalitis, tuberculous meningitis, CMV retinitis)
    • If these serious CNS infections are identified, initiation of ART is often delayed until OI is well-controlled with antimicrobials
  • IRIS is usually a self-limited syndrome as long as infection is adequately treated
    • Patients with IRIS should continue both ART and antimicrobial treatment for underlying OI
    • In severe cases, glucocorticoids can be used to decrease inflammation