Abstracts
Résumé
Les stratégies d’immunothérapie de l’infection par le VIH utilisant des cytokines ont pour objectifs d’interférer avec les mécanismes de dérégulation de l’homéostasie lymphocytaire T induits par le virus, de potentialiser les effets des antiviraux sur la restauration immunitaire et de mobiliser les réservoirs du virus. Les interleukines 2 et 7 (IL-2 et IL-7) sont les cytokines les plus prometteuses. Un bénéfice clinique potentiel de ces stratégies est l’arrêt des traitements antiviraux, dont la toxicité à long terme est une préoccupation majeure. Par ailleurs, les effets d’une telle immuno-intervention sur la régulation de l’homéostasie lymphocytaire T ou sur les fonctions immunologiques en présence du VIH nous renseignent également sur la physiopathologie de l’infection.
Summary
The theoretical objectives of cytokine therapies in HIV infection are to impact T cell homeostasis and/or to improve immune functions or the mobilization of the HIV reservoir. Among cytokines, IL-2 and IL-7 are promising agents under clinical evaluation. Intermittent administration of IL-2 is by far the furthest studied strategy in HIV infection. This cytokine increases CD4 T lymphocytes in HIV-infected individuals. Recent clinical data showed that this effect is sustained over years. IL-2 therapy induces a peripheral expansion of T cells as a consequence of prolonged survival of T cells and decreased immune activation. These effects suggest that a cytokine therapy may interfere with critical factors of HIV disease. Recent data provide arguments that IL-2 therapy improves immune functions in HIV-infected patients. Whether these effects may be translated into clinical benefits is under evaluation in ongoing phase III studies. The potential interest of IL-7 in the treatment of HIV-infection is based on its crucial role on T cell homeostasis both in thymic output and peripheral T proliferation and survival. Although no data in human are still available, recent studies provide arguments to assess this cytokine in HIV infection. Phase I studies are ongoing or planned.
Appendices
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