What is the management of Immune Reconstitution Inflammatory Syndrome (IRIS) post Antiretroviral Therapy (ART)?

Management of Immune Reconstitution Inflammatory Syndrome (IRIS) Post-ART

Continue both antiretroviral therapy and antimicrobial treatment for the underlying opportunistic infection in most cases of IRIS, adding corticosteroids only for severe manifestations. 1, 2

General Management Principles

Continue Core Therapies

• Do not alter or discontinue ART unless life-threatening complications develop 1, 2
• Maintain antimicrobial therapy for the underlying opportunistic infection 1
• The majority of IRIS cases are self-limiting and resolve with symptomatic management alone 3, 4

Exclude Alternative Diagnoses First

• Rule out treatment failure from drug-resistant organisms (particularly in tuberculosis) 1
• Exclude new opportunistic infections, malignancies (especially non-Hodgkin lymphoma), or drug toxicity 1
• Confirm immune reconstitution is occurring: decreasing HIV viral load and improving CD4 count support IRIS diagnosis rather than treatment failure 1

Severity-Based Treatment Algorithm

Mild to Moderate IRIS

• Administer NSAIDs such as ibuprofen for symptomatic relief 1, 2
• Continue ART and pathogen-specific therapy without modification 1
• Most cases resolve spontaneously within days to weeks 1

Severe IRIS

• Initiate prednisone 1.25 mg/kg/day (50-80 mg/day) for 2-4 weeks 1, 2
• Taper corticosteroids over 6-12 weeks or longer based on clinical response 1
• In a placebo-controlled trial, this dose significantly reduced hospitalization and need for surgical procedures in moderate IRIS 1
• For severe CNS manifestations, consider dexamethasone at higher doses 1

Life-Threatening IRIS

• Consider temporary interruption of ART only in life-threatening cases 4
• This is particularly relevant for CNS tuberculosis IRIS, where severe or fatal neurological complications can occur 1

Pathogen-Specific Considerations

Tuberculosis-IRIS

• Presents with high fevers, worsening respiratory symptoms, enlarging lymph nodes, expanding CNS lesions, worsening pulmonary infiltrates, new/increasing pleural effusions, or intra-abdominal abscesses 1, 2
• Occurs in 7.6% of patients, with 31% requiring hospitalization 1
• For CNS tuberculosis specifically, delay ART initiation until 8 weeks after starting tuberculosis treatment to avoid severe IRIS complications 1
• Drainage may be necessary for worsening pleural effusions or abscesses 1

Cryptococcal-IRIS

• Occurs in approximately 30% of patients with cryptococcal meningitis 1
• Manifests with fever, lymphadenitis, or CNS inflammation with increased intracranial pressure 1, 2
• Continue both ART and antifungal therapy without modification 1
• For severe symptomatic IRIS, use corticosteroids 0.5-1.0 mg/kg/day prednisone equivalent for 2-6 weeks 1
• Manage increased intracranial pressure aggressively with serial lumbar punctures; do not use corticosteroids, mannitol, or acetazolamide for ICP management 1

MAC-IRIS

• Presents as paradoxical worsening despite appropriate antimycobacterial therapy with fever and lymphadenitis 2
• Consider withholding ART until after the first 2 weeks of antimycobacterial therapy to reduce IRIS risk 2

Prevention Strategies

Timing of ART Initiation

• For tuberculosis with CD4 <50 cells/μL (non-CNS): start ART within 2 weeks of tuberculosis treatment to reduce mortality, accepting increased IRIS risk 1, 2
• For tuberculosis with CD4 ≥50 cells/μL: initiate ART at 8-12 weeks after starting tuberculosis treatment 2
• For CNS tuberculosis: delay ART for 8 weeks regardless of CD4 count 1
• For cryptococcosis, delaying ART until completion of induction therapy (first 2 weeks) is prudent, especially with elevated ICP 1

Risk Factor Mitigation

• Screen and treat opportunistic infections before initiating ART when feasible 2
• Patients with CD4 <50 cells/μL, high pathogen burden, and early ART initiation (<2 weeks) are at highest risk 1, 2, 3

Monitoring Requirements

• Monitor for new or worsening symptoms within the first 3-6 months after ART initiation 2, 3
• Track CD4 count recovery and HIV viral load suppression to confirm immune reconstitution 1, 2
• IRIS typically occurs within 3-6 months of starting ART, though timing varies by pathogen 2

Critical Pitfalls to Avoid

• Do not mistake IRIS for treatment failure and unnecessarily change antimicrobial regimens 1
• Do not use corticosteroids for managing increased intracranial pressure in cryptococcal disease 1
• Do not discontinue ART prematurely; interruption should be reserved only for life-threatening cases 4
• Avoid glucocorticoids in patients with Kaposi sarcoma, as they can cause significant disease flares 5