What is the treatment for Immunoreconstitution (IRIS) syndrome?

Treatment of Immune Reconstitution Inflammatory Syndrome (IRIS)

For immune reconstitution inflammatory syndrome (IRIS), treatment should be tailored to severity, with NSAIDs for mild to moderate cases and corticosteroids (prednisone 0.5-1.0 mg/kg/day for 4-8 weeks with gradual taper) for severe cases, while continuing antiretroviral therapy in most situations. 1

Understanding IRIS

IRIS occurs when patients with HIV initiate antiretroviral therapy (ART) and experience an exaggerated inflammatory response to a previously acquired opportunistic infection or antigen. It typically manifests within the first 3-6 months after starting ART and presents in two main forms:

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

Diagnosis and Assessment

Diagnosis of IRIS is primarily one of exclusion, requiring:

• Temporal relationship with ART initiation
• Evidence of immune recovery (increasing CD4 count, decreasing viral load)
• Exclusion of treatment failure due to drug resistance
• Exclusion of new opportunistic infections
• Clinical or radiological evidence of inflammatory response 1

Risk Factors for IRIS

• Low baseline CD4+ cell count (<50 cells/μL)
• High viral load before treatment initiation
• Rapid decrease in HIV viral load after starting ART
• Early initiation of ART after treatment for opportunistic infections
• Previous opportunistic infections 1

Treatment Algorithm

1. Mild to Moderate IRIS

• First-line: NSAIDs (e.g., ibuprofen) for symptomatic relief 1
• Continue: Both antiretroviral therapy and treatment for the underlying opportunistic infection 1
• Monitor: Assess response to NSAIDs within 1-2 weeks 1

2. Severe IRIS

• First-line: Corticosteroids - prednisone 0.5-1.0 mg/kg/day for 4-8 weeks with gradual taper 1
• Continue: Antiretroviral therapy in most cases 1
• Specific interventions based on affected organ system:
  • Respiratory: Drainage for worsening pleural effusions 1
  • CNS: Aggressive management with corticosteroids and possibly CSF drainage for increased intracranial pressure 1
  • Abdominal: Drainage of abscesses if present 1

3. TB-IRIS (Special Consideration)

• First-line: Prednisone 1.25 mg/kg/day, which has been shown to significantly reduce the need for hospitalization or surgical procedures 1
• Continue: Both antiretroviral therapy and anti-TB medications 1

4. Neurological TB-IRIS

• First-line: High-dose corticosteroids 2
• Consider: ART interruption if level of consciousness is depressed 2

Important Caveats

1. Avoid corticosteroids in viral forms of IRIS (e.g., herpes virus, CMV) as they may worsen the condition 2

2. Kaposi sarcoma-associated IRIS: Glucocorticoids are generally contraindicated as they may cause life-threatening Kaposi sarcoma exacerbation due to stimulatory effects on Kaposi sarcoma spindle cells 3

3. HIV management: Coordinate with an HIV specialist for optimal management. ART should not be delayed or discontinued unless life-threatening IRIS develops 3

4. Monitoring: Continue regular monitoring of both HIV and opportunistic infection treatment response 1

Prevention Strategies

While no established prevention strategies exist, early recognition of risk factors may allow for closer surveillance in susceptible patients 1. Optimizing therapy for opportunistic infections before ART is commenced may help prevent IRIS 4.

Special Considerations

• Tuberculosis meningitis IRIS: Potentially fatal and requires prompt recognition and treatment 1
• Timing of ART initiation: Optimal timing depends on CD4+ count, with earlier initiation recommended for those with lower CD4+ counts 1

By following this treatment approach based on IRIS severity and specific manifestations, clinicians can effectively manage this potentially serious complication of antiretroviral therapy.