The challenge of IL-2 immunotherapy in HIV disease: "no through road" or turning point?

The perception of HAART failure in achieving broadest immune reconstitution has further strengthened the rationale to widely explore new adjuvant immunotherapy. Most work has been performed on IL-2, given its potential to correct HIV-driven immune defects, possibly translating in enhanced immune competency. This is a literature review report reviewing different trials on IL-2 immunotherapy in HIV/AIDS in the past ten years through the Cochrane and NIH review database. IL-2 can benefit severely compromised patients, either HAART-naïve or lacking HAART-driven immune rescue. Furthermore, by sparing HAART-related toxicity, IL-2 is indicated within treatment interruptions or immunization protocols. Important clinical insights stem from the IL-2-mediated immune reconstitution, with a rise in long-term peripheral T-cell turnover, survival and functional markers. Furthermore, IL-2 immunotherapy proved to interfere with cytokine networks with specific regulatory functions over T-cell homeostasis and function. Despite the plethora of immunological findings exploring the intriguing hypothesis that IL-2 might contribute to amend the skewed T-cell immunophenotype and cytokine milieu in HIV/AIDS, major question on the actual clinical impact remain unanswered. This review is meant to thoroughly explore the possibility that the immunological advantages described during IL-2 immunotherapy might translate into actual clinical benefits in the treatment of HIV/AIDS disease.