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 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., 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