What is the management approach for immune reconstitution syndrome (IRIS)?

Management of Immune Reconstitution Inflammatory Syndrome (IRIS)

For patients with moderate to severe IRIS, initial treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended, followed by short-term (4-8 weeks) systemic corticosteroid therapy at doses equivalent to 20-40 mg of oral prednisone daily if symptoms do not improve with NSAIDs. 1

Understanding IRIS

IRIS is a consequence of dysregulated immune recovery that occurs after initiation of antiretroviral therapy (ART) in HIV-infected individuals. It manifests in two main forms:

• Unmasking IRIS: Presentation of a previously subclinical infection
• Paradoxical IRIS: Clinical worsening of a previously diagnosed and treated infection

Common opportunistic infections associated with IRIS include:

• Mycobacterium avium complex
• Tuberculosis
• Cryptococcosis
• Cytomegalovirus retinitis
• Pneumocystis pneumonia
• Kaposi sarcoma 1

Risk Factors for IRIS

• Low baseline CD4+ T-cell count (especially <50 cells/μL)
• High viral load before ART initiation
• Rapid decline in viral load after starting ART
• Short interval between treatment of opportunistic infection and ART initiation
• High antigenic burden of opportunistic infection 2, 3

Diagnostic Approach

IRIS should be considered when patients develop inflammatory manifestations after initiating ART, typically within 3-6 months. The reported incidence ranges from 6-39% in patients with AIDS-related conditions 1.

Key diagnostic features include:

• Temporal association with ART initiation (usually within 3-6 months)
• Evidence of immune recovery (increasing CD4 count, decreasing viral load)
• Clinical worsening of a previously recognized condition or unmasking of a subclinical infection
• Exclusion of alternative explanations (treatment failure, new infection, drug toxicity)

Management Algorithm

1. Continue ART in most cases unless life-threatening IRIS develops 1

   • Discontinuation of ART should be considered only in severe, life-threatening cases

2. First-line treatment for moderate to severe symptoms:

   • NSAIDs for initial management 1

3. If symptoms persist or are severe:

   • Short-term corticosteroids (prednisone 20-40 mg daily for 4-8 weeks) 1
   • Note: Corticosteroids are generally contraindicated in Kaposi sarcoma-associated IRIS due to potential exacerbation 1

4. Pathogen-specific therapy:

   • Optimize treatment for the underlying opportunistic infection
   • For mycobacterial infections: Continue or initiate appropriate antimycobacterial therapy 1
   • For fungal infections: Ensure adequate antifungal coverage

5. Management of CNS involvement:

   • More aggressive approach needed for CNS manifestations (especially with cryptococcal or tubercular meningitis)
   • Higher doses of corticosteroids may be required
   • Consider neurosurgical consultation for increased intracranial pressure management 3

Special Considerations

Tuberculosis-associated IRIS

• Continue TB treatment and ART
• Add corticosteroids for severe manifestations
• Monitor closely for clinical response

Cryptococcal-associated IRIS

• Particularly concerning when affecting the CNS
• Management of increased intracranial pressure is critical
• May require repeated lumbar punctures

Kaposi Sarcoma-associated IRIS

• Avoid corticosteroids as they may exacerbate Kaposi sarcoma through stimulatory effects on spindle cells 1
• Management should involve coordination with an HIV specialist
• Continue ART unless life-threatening IRIS develops

Prevention Strategies

• Optimal timing of ART initiation after treating opportunistic infections
• Earlier HIV diagnosis and treatment before severe immunosuppression occurs
• Screening for subclinical opportunistic infections before starting ART in severely immunosuppressed patients
• Initiating ART at CD4+ T-cell counts >350/μL may prevent most cases of IRIS 2

Monitoring

• Close clinical monitoring during the first 3-6 months of ART
• Regular assessment of CD4 counts and viral load
• Vigilance for new or worsening symptoms that could indicate IRIS
• Evaluation of treatment response to both ART and opportunistic infection therapy

Remember that most cases of IRIS are self-limiting, but careful monitoring and appropriate management are essential to reduce morbidity and mortality, particularly in cases involving the central nervous system or respiratory failure.