BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) represents an unexpected inflammatory response shortly after initiation of antiretroviral therapy (ART) in some human immunodeficiency virus (HIV)–infected patients with underlying neoplasia or opportunistic infections, including tuberculosis. We hypothesized that IRIS is associated with increased glycolysis and that (18)F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) could help identify high-risk subjects. METHODS: In this prospective cohort study, 30 HIV-infected patients (CD4(+) count