Immune Reconstitution Inflammatory Syndrome (IRIS)
Definition | |
Paradoxical IRIS | Paradoxical worsening of symptoms during the ART-induced immune-reconstitution period in association with inflammatory signs (by physical exam, imaging or tissue biopsy), after exclusion of the expected course of a treated/untreated OI or drug toxicities |
Unmasking IRIS | New onset of symptoms during the ART-induced immune-reconstitution period in association with inflammatory signs (by physical exam, imaging or tissue biopsy), after exclusion of the expected course of a treated/ untreated OI or drug toxicities |
Prevention | |
Cryptococcal meningitis: paradoxical IRIS | Start therapy with amphotericin B plus flucytosine and defer start of ART for at least 4 weeks |
Cryptococcal meningitis: unmasking IRIS | Determine serum cryptococcal antigen in newly diagnosed PLWH with CD4 counts < 100 cells/μL. If cryptococcal antigen is detected, exclude active cryptococcal disease, and, in particular, examine CSF to rule out cryptococcal meningitis. If meningitis is ruled out, start pre-emptive therapy. For details, see below the specific section on cryptococcal disease |
Tuberculosis: paradoxical IRIS |
Simultaneous initiation of ART and prophylactic prednisone in persons with CD4 cell count < 100 cells/μL, who started anti-TB treatment within 30 days prior to ART, may reduce risk of TB-IRIS by 30%. Prednisone dose: 40 mg qd po for 2 weeks, followed by 20 mg qd po for 2 weeks |
Treatment | |
In general, OI-IRIS resolve within a few weeks with continuation of specific treatment for the OI, without discontinuing ART and without anti-inflammatory treatment |
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TB-IRIS | Start of systemic corticosteroids is recommended (e.g., prednisone 1.5 mg/kg/day po for 2 weeks, then 0.75 mg/kg/day for 2 weeks) |
Life-threatening CNS-IRIS: TB-meningitis | Prednisone (1.5 mg/kg/day po for 2 weeks, then tapering) |
Life-threatening CNS-IRIS: PML | Methylprednisolone (1 g/day iv for 3-5 days or dexamethasone 0.3 mg/kg/day iv for 3-5 days), then oral tapering |