It is well known that recombinant interleukin-2 (IL-2) increases CD4 counts in HIV-infected persons, beyond the effect of antiretroviral therapy (ART) alone, but it has not been clear as to whether these CD4 gains translate into clinical benefit. At the 16th Conference on Retroviruses and Opportunistic Infections in Montreal in February, the long-awaited results from two large randomized clinical trials of IL-2 therapy were presented; these findings definitively answer the question.(1,2)
More than 5,800 patients already on ART were randomized to receive subcutaneous IL-2 with ART or to receive ART alone, and were followed for a median of more than 7 years. The ESPRIT study examined patients with baseline CD4 counts of ≥300 cells/µL whereas the SILCAAT study looked at patients with baseline CD4 counts of 50-299 cells/µL. The studies had somewhat different protocols, but both found statistically significantly higher CD4 cell counts in IL-2 groups than in controls, and no differences in rates of HIV RNA suppression. However, there were no differences between treatment groups in the primary study outcomes of opportunistic disease or death. Additionally, the ESPRIT study noted a higher rate of Grade 4 clinical events in the IL-2 group.
| Clinical Bottom Line|
In patients on ART, IL-2 increases the CD4 cell count but does not confer clinical benefit. Further research is needed to define possible approaches to immune-based therapies.
- Losso M, Abrams D, INSIGHT ESPRIT Study Group. Effect of interleukin-2 on clinical outcomes in patients with a CD4+ cell count of 300/mm3: primary results of the ESPRIT study. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 90aLB.
- Levy Y, SILCAAT Sci Committee. Effect of interleukin-2 on clinical outcomes in patients with CD4+ cell count 50 to 299/mm3: primary results of the SILCAAT study. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2009; Montreal. Abstract 90bLB.