Does immune reconstitution syndrome promote active tuberculosis in patients receiving highly active antiretroviral therapy?

Abstract

To assess whether highly active anti-retroviral therapy (HAART) contributes to the presentation of active tuberculosis (TB). Retrospective single-centre cohort study. A total of 111 HIV-infected individuals with active TB were identified at an urban teaching hospital between February 1997 and April 2004. Those receiving HAART at the time of TB diagnosis were assessed. Nineteen of 111 (17%) were receiving HAART when TB developed. Within this group there appeared to be two distinct populations. Thirteen of 19, 12 from ethnic or social groups with high background rates of TB, developed disease a median of 41 days (range, 7-109) after starting HAART ('early TB' group). In six of 19 ('late TB' group), TB occurred a median of 358 days after HAART initiation (range, 258-598). The 'early TB' group had lower CD4 cell counts when starting HAART in comparison with the 'late TB' group (median; 87 versus 218 x 10 cells/l; P = 0.04); however no difference was observed in the rate of change of CD4 cell count (P = 0.5) or HIV load. Paradoxical reaction rate in the 'early TB' group was significantly greater than in the 'late-TB' group (62 versus 0%, P = 0.02) and greater than in a similar control population who started HAART while taking anti-TB therapy (62 versus 30%, P = 0.05). These data suggest anti-HIV treatment may amplify the presentation of active TB. This has implications for antiretroviral programmes in countries with high TB rates and warrants prospective investigation of a larger cohort.