Background: IL-2, as an adjunct to antiretroviral therapy, increases the absolute number of CD4+ T cells in HIV-1-infected individuals.  However, the long-term clinical benefit of IL-2 treatment is unknown.  In macaques infected with SIVmac251, it is however possible to ascertain the clinical, virological, and immunological effects of IL-2 treatment. 

Methods: Here we have modeled immune intervention in SIVmac251-infected Mamu-A*01 positive and negative rhesus macaques with low doses of IL-2 in the presence of antiretroviral therapy (ART) during primary and chronic infection and investigated whether the cytokine treatment could restore immune competence, modulate virus specific immune responses, and ameliorate the virological outcome after ART interruption. 

Results: Continuous daily treatment with IL-2 during ART in both primary and chronic SIVmac251 infection was not associated with a significant increase in the frequency of virus specific CD8+ T cell response.  Surprisingly, a decrease in proliferative response to Gag was observed following IL-2 treatment.  Nevertheless, following ART suspension, continuous treatment with IL-2 contributed to the containment of viral rebound.  In addition, IL-2 treatment appeared to be associated with less frequent viral immune escape to an immunodominant SIVmac251 Gag epitope.  The effect of IL-2 was, however, transient and, once the cytokine was discontinued in chronically infected macaques, both viremia and CD4+ T-cell count returned to the pretreatment level within a few weeks. 

Conclusions: The continuous use of low dose IL-2 may be a temporary ART sparing treatment and benefit some HIV-1 infected individuals.