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Pathogenesis and identification of predictive factors of TB-IRIS in HIV patients under HAART
Framework programme:
Project number:
EC contribution:
€ 2,475,482
36 Months
Starting date:
January 2007

Keywords: Undesirable effect, ART, IRIS, developing countries, Tuberculosis, HIV


The Immune Reconstitution Inflammatory Syndrome (IRIS) is an undesirable effect of effective antiretroviral therapy (ART) in HIV-infected patients. It is a pathological inflammatory response against microorganisms, which are "recognized" as new by the regenerating immune system in response to ART. Tuberculosis-associated IRIS (TB-IRIS) is expected to become a major cause of HIV-associated morbidity as an increasing number of patients have access to ART in areas where both HIV infection and TB are endemic.

The lack of a clear-cut case-definition and reliable predictive markers make clinical management of TB-IRIS less efficient. The exact immunopathological mechanisms underlying TB-IRIS are not known. It is hereby put forward that TBIRIS occurs when immunity is unevenly reconstituted after ART and in the presence of a high burden of M tuberculosis antigens.

The overall aim of this study is to understand the pathogenesis of TB-IRIS, and to define its determinants by conducting a comprehensive investigation of clinical, virological, immunological and molecular parameters in a cohort of HIV-infected patients with different levels of exposure to TB. The occurrence of TB-IRIS will be used as the outcome variable. The clinical presentation of TBIRIS will be assessed and the predictive value of different biological markers of HIV infection and tuberculosis (including the immune response induced by the novel TB protein HBHA), will be evaluated. Parallel to the clinical studies, there will be a study on whether defective reconstitution patterns associated with TB-IRIS can be linked to 3 types of key player cells. Cellular and molecular immunology techniques to characterize aberrant restoration profiles of regulatory T cells, effector T cells and monocyte/macrophages that are associated with TB-IRIS will be used. Results will be used to formulate guidelines for the diagnosis and therapy of TB-IRIS and to define clinically relevant predictors for the occurrence of TBIRIS.

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