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Content archived on 2024-05-29

Pathogenesis and identification of predictive factors of TB-IRIS in HIV patients under HAART

Objective

Summary: 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 germs, 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. We postulate that TB-IRIS 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. We will use the occurrence of TB-IRIS as the outcome variable. The clinical presentation of TB-IRIS 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, we will examine whether defective reconstitution patterns associated with TB-IRIS can be linked to 3 types of key player cells. We will use 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. Our 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 TB-IRIS.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP6-2005-LIFESCIHEALTH-6
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Funding Scheme

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STREP - Specific Targeted Research Project

Coordinator

INSTITUTE OF TROPICAL MEDICINE
EU contribution
No data
Total cost

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No data

Participants (6)

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