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 natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVmedical and health sciencesclinical medicinepneumologytuberculosis Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2005-2.3.0-5 - Undesirable consequences of drugs and vaccines for poverty-related diseases Call for proposal FP6-2005-LIFESCIHEALTH-6 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator INSTITUTE OF TROPICAL MEDICINE EU contribution No data Address Nationalestraat 155 ANTWERPEN Belgium See on map Links Website Opens in new window Total cost No data Participants (6) Sort alphabetically Sort by EU Contribution Expand all Collapse all INFECTIOUS DISEASES INSTITUTE Uganda EU contribution No data Address Faculty of Medicine, Makerere University,Mulago Hospital Complex 22418 KAMPALA See on map Links Website Opens in new window Total cost No data UNIVERSITE LIBRE DE BRUXELLES Belgium EU contribution No data Address 50 Avenue F Roosevelt BRUSSELS See on map Links Website Opens in new window Total cost No data ACADEMIC MEDICAL CENTER Netherlands EU contribution No data Address Meibergdreef 9 22700 AMSTERDAM See on map Links Website Opens in new window Total cost No data FLANDERS INTERUNIVERSITY INSTITUTE FOR BIOTECHNOLOGY Belgium EU contribution No data Address Rijvisschestraat 120 GENT See on map Links Website Opens in new window Total cost No data INSTITUT PASTEUR DE LILLE France EU contribution No data Address Rue du Prof. Calmette, 1 245 LILLE See on map Links Website Opens in new window Total cost No data JOINT CLINICAL RESEARCH CENTRE Uganda EU contribution No data Address Butikiro House, Plot No. 893 Ring Road 10005 KAMPALA See on map Links Website Opens in new window Total cost No data
