HIV establishes a chronic infection that is marked by the progressive depletion of CD4+ T-cells, yet the mechanisms by which this depletion arises are a matter of controversy. Evidence is accumulating that T CD4+ depletion is not effected solely by virus-mediated killing and that mechanisms involving T-cell dynamics play a major role in the pathogenesis of HIV infection. Hence antiretroviral therapy, by controlling viral replication alone, invariably fails to achieve the broadest immune reconstitution. This issue has strengthened the rationale to widely explore new adjuvant immunotherapy. Most work has been performed on IL-2, given its potential to correct HIVdriven immune defects, possibly translating in a more effective immune competency. Important insights stem from the IL-2-mediated immune reconstitution pattern, with a rise in peripheral turnover and thymopoiesis, IL-7 synthesis and functional markers, resulting in the correction of the skewed T-cell immunophenotype and cytokine milieu. Combined, these findings suggest that IL-2 has a beneficial effect in correcting the severe disruption in T-cell homeostasis induced by HIV, through the interaction with T-cells and cytokine microenvironment. However, whether or not these immunologic effects translate in an actual immunologic competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.
Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases and Tropical Medicine, Ospedale San Paolo, Via di Rudini 8, 20142 Milan, Italy.