Management of Antiretroviral Therapy in Immune Reconstitution Inflammatory Syndrome
No, you should NOT stop antiretroviral therapy (ART) in patients experiencing Immune Reconstitution Inflammatory Syndrome (IRIS). Continue both ART and antimicrobial therapy for the underlying opportunistic infection unless life-threatening complications develop 1.
Core Management Principle
The fundamental approach is to continue ART while managing the inflammatory response, as the benefits of treating HIV infection outweigh the risks associated with IRIS 2. The overall mortality associated with IRIS is low, and most patients have a self-limiting disease course 3.
When to Continue ART (Standard Approach)
- For mild to moderate IRIS: Continue both ART and treatment for the underlying opportunistic infection without interruption 1
- Initiate NSAIDs (such as ibuprofen) for symptomatic relief as first-line anti-inflammatory therapy 1
- For severe IRIS manifestations: Administer prednisone 0.5-1.0 mg/kg/day (or equivalent) for 2-6 weeks with gradual taper while maintaining ART 1
- For moderate to severe MAC-associated IRIS: Use nonsteroidal anti-inflammatory agents initially; if symptoms do not improve, use short-term (4-8 weeks) systemic corticosteroid therapy in doses equivalent to 20-40 mg of oral prednisone daily 4
Rare Exception: Life-Threatening IRIS
ART interruption may be considered only in life-threatening forms of IRIS 5. This represents an extremely narrow exception to the general rule and should be reserved for:
- Patients with central nervous system involvement with raised intracranial pressure in cryptococcal or tubercular meningitis 3
- Respiratory failure due to acute respiratory distress syndrome (ARDS) 3
- Other immediately life-threatening complications where continuing ART poses imminent mortality risk 5
Critical Distinction: Prevention vs. Treatment
The evidence regarding timing of ART initiation to prevent IRIS is distinct from whether to stop ART once IRIS develops:
Prevention Strategy (Before Starting ART)
- For disseminated MAC disease: Withhold ART until after the first 2 weeks of antimycobacterial therapy to reduce drug interactions, pill burden, and IRIS complications 4, 1
- For tuberculosis with CD4 <50 cells/μL: Start ART within 2 weeks of TB treatment to reduce mortality, accepting increased IRIS risk 1
Treatment Strategy (After IRIS Develops)
- Continue ART in the vast majority of cases 1, 2
- Optimize treatment for the underlying opportunistic infection 5
- Add anti-inflammatory therapy as needed 1
Monitoring and Supportive Care
- Exclude alternative causes for clinical deterioration before attributing symptoms to IRIS 5
- Monitor for new or worsening symptoms within the first 3-6 months after ART initiation 1
- Track CD4 count recovery and viral load suppression to confirm immune reconstitution 1
- Consider therapeutic procedures (such as aspiration of pus collections) which play an important role in some patients 5
Common Pitfall to Avoid
Do not discontinue ART reflexively when IRIS is diagnosed. The presence of an IRIS response does not predict overall HIV or opportunistic infection treatment responses 2. Stopping ART would reverse the immune recovery that is ultimately beneficial for long-term outcomes, even though it temporarily causes inflammatory complications 3.
The evidence is clear and consistent across multiple guidelines: ART continuation is the standard of care for IRIS management, with discontinuation reserved only for the most severe, life-threatening presentations 1, 5, 2, 3.