Unmasked Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Disease: A Disease Spectrum after Initiation of Antiretroviral Therapy

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Abstract
Antiretroviral therapy (ART) has beneficial effects on mortality and lowers the incidence of diseases caused by opportunistic infections, such as tuberculosis (TB). AlthoughARThas sustained long-term benefits, the risk ofTB is high during the first 3 months after ART initiation. Among cases of ART-associated TB, we define “unmasked TB” as that which occurs in patients with reactivation disease who develop clinically recognizable TB after ART with the restoration of previously acquired TB antigen-specific functional immune responses. TB cases with clinical evidence of an inflammatory syndrome are a subset of these unmasked cases, which we define as “unmasked TB-immune reconstitution inflammatory syndrome.” With more widespread use of ART in areas with a high prevalence of TB, unmasked TB will likely become more common. TB diagnostics with improved sensitivity and specificity are urgently needed to detect subclinical TB before it is unmasked.