To have and have not: dissecting protective and pathologic immune recovery in TB-IRIS

Abstract

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a growing concern for advanced HIV/TB coinfected patients in an era where antiretroviral therapy (ART) is started shortly after TB treatment initiation. This perspective discusses potential mechanisms underlying TB-IRIS, focusing on recent studies that implicate coordinated recovery in adaptive and innate immune responses following ART initiation in TB-IRIS. More broadly, HIV/TB patients are probably a heterogeneous group whose outcomes are determined by the direction in which these immune responses change following ART initiation. Finally, in addition to treatment interventions that are in the pipeline for TB-IRIS, we highlight the need for holistic management of HIV/TB coinfected patients, which go beyond the current definition of TB-IRIS and take into consideration long-term consequences of robust immune recovery on ART.