The potential role of interleukin-2 in patients with HIV infection

Interleukin-2 (IL-2) is a T cell derived cytokine that leads to a sustained expansion of the CD4+ T cell pool when given as 5-day cycles approximately every 8 weeks. An extensive series of phase I/II studies have been carried out and have leaded to the initiation of two phase III trials that are currently enrolling patients in 23 countries. Studies of the mechanisms of action have revealed that IL-2 is capable of inducing the polyclonal proliferation of CD4+ and CD8+ T cells, even in the absence of expression of the high affinity IL-2 receptor. While IL-2 leads to a 6-fold increase in T cell proliferation and a 2-fold increase in T cell death, the primary mechanism of action leading to expansion of the CD4+ T cell pool appears to be an increase in CD4+ T cell survival. While early work focused on the ability of IL-2 to exert these effects in patients with relatively early stages of HIV infection, more recent work, in the setting of HAART, indicates that these effects may be seen at all stages of HIV disease. The results of the phase III studies should provide an answer to the question of whether or not this is a strategy that will be of clinical benefit.