Immune reconstitution syndrome

Some people taking antiretroviral therapy develop a syndrome known as immune reconstitution inflammatory syndrome. This is characterised by new or paradoxical worsening of tuberculosis symptoms.

This syndrome occurs among people with treated or active but silent M. tuberculosis infection who have had a strong immunological and virological response to antiretroviral therapy. As a result of immune reconstitution, the immune system attacks areas of the body where the bacteria have been lurking.¹

Symptoms may be typical, marked by a worsening of fever, coughing, shortness of breath, lymphadenopathy or worsening of signs of tuberculosis on a chest X-ray. They may also be extrapulmonary and atypical, such as unusual lymphoid swelling leading to bursting, open sores or cerebral masses.

This syndrome appears to be more widespread in resource-limited settings, where tuberculosis is most prevalent, and in patients who begin therapy with low CD4 cell counts, especially below 50 cells/mm³. Symptoms may appear within the first couple months on antiretroviral treatment, but later flare-ups have been reported.

Most experts believe antiretroviral therapy should be continued in these patients, unless the reaction is life-theatening. Patients should also receive tuberculosis treatment even though patients may have negative tuberculosis cultures.

A four-week course of corticosteroid therapy (prednisone) has been shown to reduce the need for hospitalisation and outpatient care, as well as reducing symptoms and inflammatory markers, in  arndomised study in 110 patients diagnosed with TB-IRIS according to a standard clinical definition in South Africa. Patients who received corticosteroids did not suffer an excess of adverse events or infections.²