Tuberculosis associated immune reconstitution inflammatory syndrome in patients infected with HIV: meningitis a potentially life threatening manifestation

Background: Tuberculosis (TB) is the most common co infection in HIV-infected persons in India, requiring concomitant administration of anti TB and antiretroviral therapies. Paradoxical worsening of tuberculosis after anti-retroviral therapy (ART) initiation is frequently seen. Objective: To study the frequency, clinical presentation and outcome of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV infected patients in a TB hospital in North India. Design: A retrospective chart review of HIV-infected TB patients on anti-tubercular treatment (ATT) at time of ART initiation over a 3 year period. Medical records were reviewed for clinical manifestations and outcome in patients who developed TB-IRIS. Results: 514 HIV-infected patients were enrolled between January 2006 and December 2008. Thirteen (12.6%) of 103 patients who had received ART and ATT simultaneously developed paradoxical TB-IRIS. Clinical presentations of paradoxical TB-IRIS included new lymphadenopathy (n = 3), increase in size of existing lymphadenopathy (n = 3), worsening of existing pulmonary lesions (n = 2), appearance of new pleural effusion (n = 1) and prolonged high grade fever (n = 2). Four patients developed new tubercular meningitis as manifestation of TB-IRIS. Our cases developed TB-IRIS a median of 15 days after starting ART (IQR 15-36). TB-IRIS patients were older (> 35 years) than those with no IRIS (P = 0.03), but were not distinguishable by CD4 T-cell count, duration of ATT before ART or the outcome of TB treatment. Eight (62%) patients had a complete recovery while 5 (38%) patients with TB-IRIS died, of which majority (n = 3) had meningitis. Conclusions: Paradoxical TB-IRIS is a frequent problem during concomitant ATT and ART in HIV-TB co infected patients in north India. Meningitis is a potentially life threatening manifestation of TB-IRIS.