Immunopathogenesis and diagnosis of tuberculosis and tuberculosis- associated immune reconstitution inflammatory syndrome during early antiretroviral therapy

Julian H. Elliott, Khol Vohith, Sarun Saramony, Chin Savuth, Chan Dara, Chel Sarim, Sarah Huffam, Robert Oelrichs, Pouv Sophea, Vonthanak Saphonn, John Kaldor, David A. Cooper, Mean Chhi Vun, Martyn A. French

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Background: In many settings, the benefits of antiretroviral therapy (ART) are reduced by the high early incidence of tuberculosis and tuberculosis- associated immune reconstitution inflammatory syndrome (TB-IRIS). Methods: We used tuberculin skin testing and the QuantiFERON-TB Gold In-Tube assay to investigate cellular immune responses to purified protein derivative (PPD) and region of difference 1 (RD1) antigens during the first 24 weeks of ART. Results: TB-IRIS and ART-associated tuberculosis occurred in 15 of 75 (20%) and 11 of 231 (4.8%) participants at risk, respectively. Greater increases in interferon γ (IFN-γ) and skin test responses to PPD were seen at week 24 and 12 in participants with TB-IRIS (P ≤ .04), respectively. Raw IFN-γ responses to RD1 antigens and PPD corrected for pre-ART CD4+ T cell counts were higher at all time points in individuals with ART-associated tuberculosis (P ≤ .001) and were associated with areas under receiver operator characteristic curves of 0.90 for RD1 (95% confidence interval [CI], 0.78-1.00) and 0.92 for PPD (95% CI, 0.83-1.00) for the diagnosis of ARTassociated tuberculosis. Pre-ART IFN-γ responses enabled stratification of participants into groups with risks of subsequent tuberculosis of 0.7%, 9.3%, and 30.0%. Conclusions: Type 1 effector T cell responses are prominent in ART-associated tuberculosis, but additional immune defects may be more important in paradoxical TB-IRIS. IFN-γ release assays may contribute to the prediction and diagnosis of tuberculosis during early ART.

Original languageEnglish
Pages (from-to)1736-1745
Number of pages10
JournalThe Journal of Infectious Diseases
Issue number11
Publication statusPublished - Nov 2009

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