Low-dose daily interleukin-2 immunotherapy: accelerating immune restoration and expanding HIV-specific T-cell immunity without toxicity

There is now a great deal of interest in therapies focused on improving the function of the immune system in the treatment of individuals infected with the HIV. Although the antiviral drugs effectively suppress replication of the virus, they cannot cure the infection. Therefore, it now appears that both antivirals and immune system stimulants will be necessary to maximally suppress residual latent virus, thereby allowing the discontinuation of the antivirals without relapse of detectable plasma virus. Interleukin-2 (IL-2) the first cytokine to be discovered at the molecular level has been used as a therapeutic in HIV infection, because it is critical for a normal functioning immune response. IL-2 is essential for the survival and proliferative expansion of antigen-activated T cells and natural killer (NK) cells, and also for promoting their differentiated functions of cytokine secretion and cytolysis. However, as IL-2 stimulates both the innate and acquired immune responses, when used as a therapeutic it can lead to severe toxicity when given in high doses. This review focuses on low dose, daily IL-2 therapy, used to accelerate the recovery of the immune system when viral replication is suppressed maximally with antivirals. In addition, the principles of the use of IL-2 to activate HIV-specific immune reactivity are discussed. At least two signals are required to promote the proliferative expansion and function of antiviral effector lymphocytes, HIV antigens and IL-2.