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
- 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
- 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.