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

Antiretroviral therapy (ART) has beneficial effects on mortality and lowers the incidence of diseases caused by opportunistic infections, such as tuberculosis (TB). Although ART has sustained long-term benefits, the risk of TB 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.