12.7 Immune reconstitution inflammatory syndrome (IRIS)

Immune reconstitution inflammatory syndrome (IRIS) occurs after initiation of ART, in the presence of a previously unrecognized, often subclinical, opportunistic infection. Patients present with paradoxical worsening of their clinical status as the immune system recovers on ART.

Symptoms vary according to the infection, but can include fever, enlarging lymph nodes, worsening pulmonary infiltrates, respiratory distress, neurologic signs, or exacerbation of inflammatory changes at other sites.

IRIS can occur anytime between 10 and 180 days after ART initiation (usually 2-4 weeks) and is more common with CD4 count < 50. Mild to moderate forms of IRIS are relatively common in TB patients who are started on ART (seen in up to one third of patients in some studies); however, severe IRIS is relatively rare.

IRIS occurs with respect to TB in two circumstances:
1 - Paradoxical TB IRIS: A patient is diagnosed with TB, starts TB treatment, followed by ART after a few weeks, and then develops IRIS.
2 - Unmasking TB IRIS: A patient is screened for TB before initiation of ART and no TB is found. The patient then starts ART, followed by onset of TB symptoms and signs.

It is important to note that IRIS with respect to TB is a diagnosis of exclusion. Patients with advanced HIV infection may show clinical deterioration for a number of other reasons (all of which should be ruled out before giving the diagnosis of IRIS):
– Clinical worsening due to new opportunistic infections;
– Other subclinical infections unmasked following immune reconstitution with ART initiation;
– TB treatment failure due to DR-TB.

The management of IRIS depends on the clinical status of the patient and the site and extent of involvement. Nonsteroidal anti-inflammatory drugs are used in mild to moderate IRIS cases and corticosteroids in severe IRIS cases (Chapter 9, Section 9.3). The use of corticosteroids can be dangerous if IRIS is misdiagnosed and the clinical deterioration is in fact DR-TB or a different opportunistic infection.

Most cases of IRIS can be treated without interruption of ART; in very severe forms of IRIS, ART may need to be suspended.