Immune Reconstitution Inflammatory Syndrome (IRIS)

Paradoxical worsening ("Paradoxical IRIS") or new onset ("Unmasking IRIS") 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
Cryptococcal meningitis: paradoxical IRIS Start therapy with amphotericin B plus flucytosine and defer start of ART for 4-6 weeks
Cryptococcal meningitis: unmasking IRIS

Determine serum cryptococcal antigen in persons newly HIV-diagnosed or unsuccessfully treated with CD4 counts < 100 cells/μL. If cryptococcal antigen is detected, 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
paradoxical IRIS
Prophylactic prednisone (40 mg qd po for 2 weeks, followed by 20 mg qd po for 2 weeks) may be considered as it reduced the risk of TB-IRIS by 30% in persons with CD4 cell count < 100 cells/μL and no TB meningitis or rifampin resistance who started anti-TB treatment within 30 days prior to ART

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 life-threatening or other 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 Prednisone
1.5 mg/kg/day po for 2 weeks, then 0.75 mg/kg/day for 2 weeks
PML-IRIS Methylprednisolone
1 g/day iv for 3-5 days or dexamethasone 0.3 mg/kg/day iv for 3-5 days, then oral tapering