4th International AIDS Society Conference on HIV Pathogenesis and Treatment Sydney, Australia - July 22 - 25, 2007

TUBERCULOSIS-ASSOCIATED IMMUNE RESTORATION DISEASE IS ASSOCIATED WITH INCREASED PPD-SPECIFIC T CELL RESPONSES DETECTED BY A WHOLE BLOOD INTERFERON-γ RELEASE ASSAY

IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Abstract No. MOAB101

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-γ 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-γ 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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2007-07-22
MOAB101
TB / HIV: Still a Deadly Partnership

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