The end of the line for IL-2
1 October 2009. Related: Basic science.
Richard Jefferys, TAG
Results from two large randomised studies of interleukin-2 (IL-2) have been published in the New England Journal of Medicine. The data were first presented earlier this year at CROI in Montreal. The trials were SILCAAT, which enrolled 1,695 people with CD4 counts between 50 and 299, and ESPRIT, which enrolled 4,111 people with CD4 counts over 300. In neither case did the addition of IL-2 offer any clinical benefits compared to antiretroviral therapy alone, despite increasing CD4 T cell counts. The results indicate that expanding CD4 T cell numbers with IL-2 does not confer added benefit beyond the increase in CD4 T cells caused by suppression of HIV replication. The researchers note that CD4 T cells induced by signaling through the IL-2 pathway may be functionally compromised and/or have a phenotype (e.g. suppressive) or specificity that is not clinically beneficial. An alternative or overlapping explanation is that the increased rate of adverse events associated with receipt of IL-2 counterbalanced any benefit from CD4 increases.
Although the results have been seen as a blow to immunebased therapy (IBT) development in HIV, they do not necessarily mean that other approaches to increasing CD4 T cell numbers (such as IL-7 or growth hormones) will suffer the same fate. The outcomes of SILCAAT and ESPRIT do however stress the need to evaluate IBTs for clinical benefit. As there are individuals who experience poor CD4 T cell reconstitution despite HIV suppression (sometimes called discordant responders) who remain at increased risk for illness, there is still a potential need for IBTs. Trials evaluating the clinical benefit of newer IBTs in this population should be feasible and would not necessarily require the large numbers involved in SILCAAT and ESPRIT.
TAG Basic Science Blog (21 Oct 2009)
INSIGHT–ESPRIT Study Group and SILCAAT Scientific Committee. Interleukin-2 therapy in patients with HIV infection. New England Journal of Medicine, Volume 361:1548-1559, October 15, 2009, Number 16.