Immune Reconstitution Inflammatory Syndrome (IRIS)

Definition  
Paradoxical IRIS Paradoxical worsening 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 [1]
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 [1]
Prevention  
Cryptococcal meningitis: paradoxical IRIS Start therapy with amphotericin B plus flucytosine and defer start of cART 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 the 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 for 2 weeks, followed by 20 mg qd for 2 weeks [2]
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.
In cases where anti-inflammatory treatment is contemplated by the physician, corticosteroids or non-steroidal anti-inflammatory agents can be used. However, little or no data support their use or specific administration schedules in the specific conditions
TB-IRIS Start of systemic corticosteroids is recommended (e.g., oral prednisone 1.5 mg/kg/day for 2 weeks, then 0.75 mg/kg/day for 2 weeks) [3]
Life-threatening CNS-IRIS:  TB-meningitis Oral prednisone (1.5 mg/kg/day for 2 weeks, then tapering) [4]
PML iv methylprednisolone (1 g/day for 3-5 days or iv dexamethasone 0.3 mg/kg/day for 3-5 days), then oral tapering