After years of studies and millions of dollars, 2009 saw the death knell for IL-2 (Interleukin-2). A presentation at CROI in February 2009 showed pooled data from ESPRIT and SILCAAT, the two largest and most expensive studies that many hoped would prove effectiveness of the first immune-based therapy for HIV. Despite transient increases in CD4 cells, more side effects were seen in the arms with IL-2 compared to placebo. IL-2 also proved to be highly toxic, resulting in several participants stopping the studies.
Project Inform and others had advocated for development of IL-2 despite several significant setbacks and frustrating pitfalls along the way. In the end, it was a depressing end to one of the brightest hopes for an immune-based therapy for HIV. However, the loss of IL-2 has set the stage for another cytokine therapy, IL-7, waiting in the wings and now making its debut.
As with IL-2, IL-7 is a naturally occurring immune chemical, or cytokine, produced by our bodies. It is important for regulating the thymus, producing important types of T cells and balancing of the immune system. The rationale for its use in HIV is compelling and several studies are beginning to show it most likely will upstage IL-2. Cytheris, a French biotech company has a patent for the next IL-7 version, now in Phase 2 studies.
An early study has provided proof of concept, dosing and safety information of IL-7 in order to move into larger studies. At the 2009 ICAAC, an interim analysis of a small Phase 2 placebo controlled study was presented. IL-7 showed safety and tolerability in this new version.
This formulation is thought to provide a longer half life and make the drug more stable. A few individuals experienced a small though short-lived increase in their viral loads, yet sustained increases of CD4 cells were reported as well as trends toward higher production of immune cells from the thymus. So far this therapy seems safer than IL-2.
The hope for IL-7 is to restore important and functional CD4 and CD8 cells when there have been wide variations in CD4 gains despite viral control with HIV therapy. And, as people live longer with HIV there becomes more pressing need to restore the immune system. In these people and others, HIV therapy alone is not the answer and immune based therapies will become more important.