What is the recommended management for patients experiencing HIV Immune Reconstitution Inflammatory Syndrome (IRIS)?

Management of HIV Immune Reconstitution Inflammatory Syndrome (IRIS)

For patients experiencing HIV Immune Reconstitution Inflammatory Syndrome (IRIS), initial treatment should begin with nonsteroidal anti-inflammatory drugs (NSAIDs), followed by short-term systemic corticosteroids (prednisone 20-40 mg daily for 4-8 weeks) if symptoms do not improve. 1, 2

Understanding IRIS

IRIS is a dysregulated immune recovery that occurs after initiation of antiretroviral therapy (ART) in HIV-infected individuals. It typically manifests within 3-6 months of starting ART, with an incidence ranging from 6-39% in patients with AIDS-related conditions 1.

IRIS can present in two forms:

• Paradoxical IRIS: Worsening of a previously treated opportunistic infection
• Unmasking IRIS: Emergence of a previously subclinical infection

Common opportunistic infections associated with IRIS include:

• Mycobacterium avium complex (MAC)
• Tuberculosis (TB)
• Cryptococcosis
• Cytomegalovirus retinitis
• Pneumocystis pneumonia
• Kaposi sarcoma

Diagnostic Approach

Diagnosis of IRIS requires:

• Temporal association with ART initiation
• Evidence of immune recovery (increasing CD4 count)
• Clinical worsening of a previously recognized condition or unmasking of a subclinical infection
• Exclusion of alternative explanations (treatment failure, new opportunistic infection)

Management Algorithm

Step 1: Continue ART in most cases

• ART should generally be continued unless life-threatening IRIS develops 1
• Discontinuation of ART should only be considered in severe, life-threatening cases, particularly with neurological involvement and depressed consciousness 2, 1

Step 2: Treat underlying opportunistic infection

• Optimize treatment for the underlying opportunistic infection
• For mycobacterial infections, continue or initiate appropriate antimycobacterial therapy 1

Step 3: Symptomatic management

For mild to moderate symptoms:

• NSAIDs as first-line therapy 2, 1

For moderate to severe symptoms that don't respond to NSAIDs:

• Corticosteroids (prednisone 20-40 mg daily for 4-8 weeks) 2, 1, 3
• Evidence from randomized controlled trials supports the use of prednisone for TB-IRIS 2, 3

Special Considerations

For TB-IRIS with CNS involvement:

• Higher doses of corticosteroids
• Consider neurosurgical consultation for increased intracranial pressure management 1
• Consider ART interruption if level of consciousness is depressed 2

For MAC-IRIS:

• Optimize antimycobacterial therapy
• NSAIDs for mild symptoms
• Corticosteroids for moderate to severe symptoms 2

For Kaposi sarcoma-IRIS:

• Avoid corticosteroids due to potential exacerbation 1

Monitoring

Close clinical monitoring is essential 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 1

Cautions and Pitfalls

• Ensure diagnosis of IRIS is certain before initiating corticosteroids, as they have significant side effects 3
• Avoid corticosteroids in viral forms of IRIS generally 3
• Don't confuse IRIS with treatment failure, antimicrobial resistance, or a new opportunistic infection 1, 3
• Remember that IRIS can occur in HIV-negative patients as well, particularly those recovering from immunosuppression 4

The management of IRIS requires balancing control of the inflammatory response with the benefits of continued immune recovery. While IRIS can cause significant morbidity, it does not generally predict poor overall HIV treatment outcomes, and ART should typically be continued while managing the inflammatory response 5.