Immune Reconstitution Inflammatory Syndrome (IRIS)

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IRIS is a phenomenon associated with the occurrence or worsening of opportunistic  infections/malignancies  which  can  occur  early  after  initiation  of  ART  or  at  later  (several  months)  during ART. There is an increased risk for occurrence of IRIS in the following situations:  

  • Treatment naïve patients  
  • Patients with advanced HIV disease with CD4 cell count < 50 cells/mm3  
  • Patients with undiagnosed and untreated opportunistic conditions 
  • Patients who have been introduced on ART before or shortly after initiation of treatment of opportunistic infection/malignancy 
  • In the advent of DTG use, there is increased likelihood for IRIS because of rapid HIV viral load suppression. 

Note: Any OI, malignancy and autoimmune diseases may present as IRIS 

Diagnostic Criteria: 

The criteria for making a diagnosis of IRIS are delineated below: 

Diagnosis of IRIS would require: 

Both major (A plus B) criteria or criterion A plus 2 minor criteria 

Major criteria 

  1. A typical  presentation  of  “opportunistic  infections  or  tumours”  in  patients  responding  to  anti-retroviral therapy (ART) includes: 
    • Localized disease e.g. lymph nodes, liver, spleen 
    • Exaggerated  inflammatory  reaction  e.g.  severe  fever,  with  exclusion  of  other  causes  of painful lesions 
    • Atypical inflammatory response in affected tissues e.g. granulomas, suppuration, necrosis, perivascular lymphocytic inflammatory cell infiltrate 
    • Progression  of  organ  dysfunction  or  enlargement  of  pre-existing  lesions  after  definite, clinical improvement with pathogen specific therapy prior to commencement of ART and  exclusion of treatment toxicity and new diagnoses 
    • Development  or  enlargement  of  cerebral  space  occupying  lesions  after  treatment  for  cerebral cryptococcus or toxoplasmosis 
    • Progressive pneumonitis or the development of organizing pneumonia after treatment of pulmonary-TB or PCP 
    • New onset or worsening of uveitis/vitritis after resolution of CMV retinitis 
    • Fever  and  cytopenia  after  treatment  for  disseminated  Mycobacterium avium  complex (MAC) disease 
    • Enlargement of Kaposi’s sarcoma lesions and subsequent resolution or partial regression without 
    • Commencement of radiotherapy, systemic chemotherapy or intralesional therapy 
  2. Decrease in plasma HIV-RNA level by > 1 log base ten copies/ml (1 log drop = 9/10 of Baseline VL copies). This applies in settings where baseline VL is performed.   

Minor criteria 

  • Increased blood CD4+ cell count after initiation of ART 
  • Increase  in  immune  response  specific  to  the  relevant  pathogen  e.g.  delayed  type hypersensitivity to mycobacterial antigens (PPD conversion) 
  • Spontaneous  resolution  of  disease  without  specific  antimicrobial  therapy  or  tumour chemotherapy with continuation of anti-retroviral therapy. 

Treatment of IRIS 

Mild to moderate forms: 

  • Reassure the patient and do not stop ART 
  • Provide specific treatment for the opportunistic infections/malignancies or other diseases 

Severe life-threatening IRIS 

  • Reassure the patient and Stop ART temporarily 
  • Provide high doses of prednisolone 1mg/kg for 4 weeks then taper down the dose
  • Provide  other  appropriate  supportive  measures  such  as  management  of  fever,  oxygen therapy, i.e. fluids 
  • Restart ART when the patient stabilizes

Note: When using high dose steroids, it is important to rule out Strogyloides stecolaris infection to avoid  disseminated strongylodiasis.