The progressive tissular accumulation of iron in HIV infection has deleterious consequenses. Therefore more studies are needed on:
- mechanisms by which iron and its chelation modulate oxidative stress and HIV-1 replication;
- effects of iron-lowering drugs on AIDS-related opportunistic pathogens;
- effects of iron chelation in HIV-infected patients.
Iron is known to progressively accumulate in several tissues of HIV-infected patients, such as the macrophages. This excessive iron burden leads to an increased oxidative stress, a decreased host defence and a stimulation of the growth of many AIDS-related opportunistic pathogens. The proposed investigors' network will study:
1- The mechanisms by which iron or its chelation (by the natural ferritin or by iron chelators) modulates oxidative stress and HIV-1 replication.
2- The activities of iron chelators from different classes and of drugs that lower cytosolic iron concentration on AIDS-related opportunistic pathogens from bacterial (Mycobacterium tuberculosis and M. avium), fungal (Cryptococcus neoformans and Candida albicans) and protozoal (Leishmania spp.) origin.
3- The effects of iron chelation therapy in HIV-1 infected patients. The first investigation will concern the effects of desferrioxamine on viral load and plasma cytokine patterns; depending on the results of this pilot study, other investigations will follow.