The immunomodulatory role of prednisone in patients with HIV-associated tuberculosis and assessment of its impact on lung function outcome

Cari Stek’s thesis assesses the effect of prednisone on immunopathology and lung function in HIV-associated tuberculosis and tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). She uses data collected during the PredART trial, a randomised, double-blind placebocontrolled trial assessing the efficacy of prednisone to prevent TB-IRIS. She uses latent class analysis to assess the performance of the current case definition for TB-IRIS and explores possibilities for its improvement. She assesses associations between cytokine profiles, lta4h genotype, development of TBIRIS and use of prophylactic prednisone. She demonstrates an association of cytokines related to the innate immune system and the development of TB-IRIS and that prednisone results in reduced concentrations of these cytokines. She reviews mechanisms of lung damage in tuberculosis and potential strategies to prevent it, and she assesses the effects of TB-IRIS and prednisone on lung function, finding neither TB-IRIS nor prednisone affect long term lung function outcomes