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Tuberculosis-associated immune restoration disease is associated with increased PPD-specific T cell responses detected by a whole blood interferon-γ release assay
Presented by Julian H Elliott, Australia.
Elliott J.H.1, Sarun S.2, Chin S.3, Chan D.3, Chel S.2, Huffam S.2, Oelrichs R.4, Hun C.2, Pouv S.2, Teng K.H.2, Teng H.2, Saphonn V.2, Kaldor J.1, Cooper D.1, French M.5, Mean C.V.2
1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia, 2National Center for HIV/AIDS, Dermatology and STDs, Ministry of Health, Phnom Penh, Cambodia, 3National Institute of Public Health, Ministry of Health, Phnom Penh, Cambodia, 4World Bank, Global HIV/AIDS Program, Washington D.C., United States, 5University of Western Australia, Perth, Australia
Objectives: Tuberculosis-associated Immune Restoration Disease (TB-IRD) is a significant complication of early antiretroviral therapy (ART) in high TB incidence settings. We aimed to characterise TB-IRD and the potential role of simple tests in the diagnosis of TB-IRD.
Methods: In a prospective cohort study of HIV-infected adults commencing ART at an ambulatory clinic in Phnom Penh, Cambodia, we administered tuberculin skin tests (TSTs) and undertook QuantiFERON-TB Gold In-Tube assays with PPD and RD1 antigens prior to ART, at months 1, 3 and 6 of treatment, and at the time of suspected mycobacterial disease, including IRD.
Results: Of 155 enrolled adults, 83 (54%) were male, median age was 33 years, median pre-ART CD4+ cell count 61 cells/mm3 and 123 (79%) patients were in WHO stage 3 or 4. Fifty-three episodes of mycobacterial disease were documented in 46 (30%) patients. Of the 27 patients commencing ART during TB treatment, six (22%) developed ‘paradoxical’ TB-IRD, two required prednisolone therapy and one patient died. In multivariate analyses, the only factor associated with development of TB-IRD was WHO stage 4 disease (OR 19.83; p=0.01). Pre-ART interferon-g release in response to PPD, RD1 and a mitogen positive control did not differ between groups. After one month of ART responses to both PPD and RD1 antigens were significantly higher in patients developing TB-IRD (p=0.04 and p<0.001 respectively). Median PPD responses increased 70-fold in the TB-IRD group and only 2-fold in those without TB-IRD. A smaller, non-significant trend was seen in TST response. Overall, antigen responses remained relatively stable after the first month of ART.
Conclusions: We report the first evidence to suggest that simple whole blood interferon-g release assays may have a role in the diagnosis of TB-IRD. Further research is urgently needed to define the potential contribution of these assays to reducing morbidity and mortality during early ART in resource-limited settings.
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