TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important complication of the management of TB-HIV co-infected patients. ART causes immune recovery and TB-IRIS follows an exaggerated immune response to persistent TB antigen or viable bacilli.

IRIS typically presents within three months of the initiation of ART but can occur as early as five days. It may occur in up to a third of persons with tuberculosis who initiate ART.

Paradoxical TB-IRIS: usually presents as a worsening of clinical symptoms after initial improvement with TB treatment. Most common clinical manifestations are reoccurrence of constitutional symptoms such as general malaise, fever, loss of weight and worsening of pre-existing lymphadenopathy or respiratory disease. Other possible manifestations are: abscess formation, CNS or hepatic involvement, pericardial effusions, etc.

Another form of immune reconstitution syndrome is the unmasking type. In this type of immune reconstitution patients had undiagnosed TB before the start of ART and TB symptoms only appeared after the start of ART. An international consensus on case definitions for TB-IRIS preferred to call this “ART-associated TB” rather than TB IRIS since it doesn’t necessarily implicate an exagerated immune response.

The paper on case definitions for TB IRIS in resource limited settings can be found on the following link: Meintjes et al. Lancet Infect Dis. 2008 Aug;8(8).

© Graeme Meintjes

Several reports suggest that paradoxical IRIS is more common if ART is started early in the course of TB treatment and in patients with low CD4 counts. Most cases resolve without any intervention and ART can be safely continued. Serious reactions such as tracheal compression, caused by massive adenopathy, or respiratory failure due to extensive pulmonary infiltrates, may occur and can be life-threatening. In that case corticosteroids are recommended. Since most cases of TB IRIS are self-limiting and not associated with increased mortality, the risks of TB-IRIS must be balanced against the benefits of early initiation of ART in severely immunodeficient patients.

A randomized controlled trial conducted in Cape Town showed a beneficial effect of steroids in TB-IRIS. One concern, however, was the frequency of MDR-TB among the TB-IRIS cases (10%), with a risk of fulminant MDR-TB when treated with steroids (Meintjes G et al. AIDS 2010).

We strongly recommend for further reading the following articles on diagnosis and management of TB IRIS: