Immune Reconstitution Inflammatory Syndrome (IRIS)

As general principles:

- risk of paradoxical IRIS can be reduced by appropriately treating cryptococcal meningitis with an optimal regimen including a fungicidal agent and by deferring ART initiation for 4 to 6 weeks.

- unmasking IRIS can be prevented by avoiding ART initiation in undiagnosed cryptococcal meningitis. Therefore, all patients with CD4 T cell counts<100 cells/ µL should be screened for serum cryptococcal antigen, and those with positive results should undergo lumbar puncture to rule out cryptococcal meningitis. Refer also to the specific section on cryptococcal disease.

TB meningitis: Corticosteroids  are recommended as adjuvant treatment (see also Diagnosis and Treatment of TB in Persons with HIV), but their efficacy to prevent paradoxical IRIS is not established.

TB without meningitis: Consider prophylactic prednisone (40 mg qd po for 2 weeks, followed by 20 mg qd po for 2 weeks) in persons with:

• CD4 cell count < 100 cells/µL AND
• who start ART within 30 days after the start of anti-TB treatment AND
• Treated with an optimal anti-TB regimen and clinically responding to antituberculous treatment ⁱ

ⁱ In the reference clinical trial (N Engl J Med 2018;379:1915-1925) persons with rifampin-resistant TB were excluded. In case of optimally-treated rifampin-resistant TB, prophylactic prednisone for IRIS prevention may be considered.

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

Cryptococcal meningitis-IRIS