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6.4 Immune Reconstitution Inflammatory Syndrome (IRIS)

Table of Contents

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 the course of 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

NB: Any OI may present as IRIS

Diagnostic Criteria:

The criteria for making a diagnosis of IRIS are delineated in Table 6.8:

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.

Table 6.9: Immune Reconstitution Inflammatory Syndrome

Diagnosis of IRIS would require:

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

Major criteria

A. 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

B. 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.

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