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The rise and fall of intermittent interleukin-2 therapy in HIV infection

Giulia Della Chiara¹, Claudio Fortis², Giuseppe Tambussi³, Guido Poli^1,4

1 AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy
2 Diagnostics of Tuberculosis, Vaccine and Immunotherapy of Infectious Diseases Units, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy
3 Clinic of Infectious Diseases, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy
4 School of Medicine, Vita-Salute San Raffaele University, Milano, Italy

* Corresponding Author: G. Poli,

European Cytokine Network 2010, 21(3), 197-201. https://doi.org/10.1684/ecn.2010.0199

Accepted 23 June 2010;

Abstract

In 1995, a breakthrough paper showed that intermittent cycles of interleukin-2 (IL-2), together with suboptimal ART, caused an unprecedented, stable increase in CD4+ T cell counts, without altering the steady state levels of viremia. At the time, this was somewhat obscured by the first successes of combination antiretroviral therapy (cART). However, since then, numerous studies have confirmed this basic finding, open-ing up a new perspective in the long-term management of chronic HIV infection. One of the benchmarks of this experimental treatment is the expansion of CD4⁺ CD25⁺ T lymphocytes probably including T regulatory cells (Tregs). Based on these encouraging findings, two major phase III clinical trials, ESPRIT and SILCAAT, involving thousands of patients worldwide, were launched and continued over several years. Unfortunately, they both resulted in the highly unexpected, yet unequivocal, outcome of a lack of a protective effect of IL-2-expanded CD4⁺ T cells on HIV disease progression towards the acquired immunodeficiency syndrome (AIDS) or death. In addition, there was the suggestion of an increase in certain deleterious effects on treated patients in terms of cardiovascular and inflammatory events. While IL-2 therapy is unlikely to be studied any further in the context of HIV infection, other cytokines, such as IL-7, are still being tested in the hope of more promising results.

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