Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap?
Highly active antiretroviral therapy (HAART) induces a substantial control of HIV viral replication, but it allows for only a partial immune reconstitution, thus prompting the rationale for the adjuvant use of immunomodulants. Based on its in vitro action as a major T cell growth factor, interleukin (IL)-2 has now been extensively investigated for its potential to correct the HIV-driven immune deficiencies, possibly translating into immunological control over HIV infection. Specific immunological end points have thus far been addressed within extensive Phase I/II trials, disclosing a broad insight into several aspects of the IL-2-mediated immune reconstitution allowing for interesting clinical speculation. Indeed, preliminary results indicate that adjuvant IL-2 induces a significant CD4 cell rescue in patients with no immune recovery following long-term HAART, thus standing as a valid and safe therapeutic option for these patients. Furthermore, in these patients, the IL-2-mediated immune reconstitution is characterized by a rise in both peripheral turnover and de novo T cell synthesis, with reversion of the skewed HIV-driven immunophenotypic pattern, a substantial increase in IL-7 production and in several markers of immune function. Combined, these findings indicate 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 immunological effects translate into an actual immunological competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.
Marchetti
Giulia
G
Institute of Infectious Disease and Tropical Medicine, University of Milan, 'Luigi Sacco' Hospital, Milan, Italy. giulia.marchetti@unimi.it
Franzetti
Fabio
F
Gori
Andrea
A
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D017024:Chemotherapy, Adjuvant; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use
D007376:Interleukin-2