Cytokine-based modulation of immune function in HIV infection.

PURPOSE OF REVIEW

Immunomodulatory strategies using cytokines have been proposed in the treatment of HIV infection. The theoretical objectives of these approaches are to impact T-cell homeostasis and improve immune functions or the mobilization of the HIV reservoir. Among cytokines IL-2 and IL-7 are promising agents under clinical evaluation. IL-2 therapy is by far the most studied strategy in HIV infection. This cytokine increases CD4 T lymphocytes in HIV-infected individuals.

SUMMARY

Recent clinical data showed that this effect is sustained over years. Most recent studies support the notion that IL-2 therapy induces a peripheral expansion of T cells as a consequence of the prolonged survival of T cells and decreased immune activation. These effects suggest that a cytokine therapy may impact critical factors of HIV disease. Recent data provide arguments that IL-2 therapy combined with highly active antiretroviral therapy improves immune functions. Whether these effects may be translated into clinical benefits is under evaluation in ongoing phase III studies. The potential interest in IL-7 for the treatment of HIV infection is based on its crucial role on T-cell homeostasis, both in thymic output and peripheral T-cell proliferation and survival. Although no data in humans are yet available, recent studies have provided arguments in favour of evaluating the potential interest in this cytokine for treatment of HIV infection. Phase I studies are ongoing or planned.