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 |