A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition

Background & objectives: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. Methods: Retrospective analysis of antiretroviral treatment (ART) naive adults started on highly active ART (HAART) from June 2006 to September 2008 was done. Results: Of the 627 patients studied, 237(38%) had TB at the initiation of HAART. In total, 18(7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95(52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Interpretation & conclusions: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB-associated IRIS.