IL-2 effectively increases CD4 count in people with low CD4 nadir

Two large ongoing investigator led studies are evaluating the role of interleukin-2 (IL-2) as an immune modulator in persons with treated HIV infection. The studies, known as SILCAAT and ESPRIT, are not simply evaluating CD4 numbers but are also looking for clinical endpoints (such as new HIV related infections, AIDS defining events and deaths). IL-2 is administered subcutaneously twice-daily for “cycles” of five days with subsequent cycles being given every eight weeks.

As with the administration of enfuvirtide (T-20) some patients administering IL-2 experience injection site reactions. In general, the severity of the symptoms declines with each cycle. IL-2 is a messenger normally produced by CD4 cells which affects both the activation of CD8 cells and causes expansion of CD4 numbers. Evidence from the pre HAART era suggested that the use of IL-2 was associated with a modest reduction in the risk of opportunistic disease events.

The SILCAAT study is an international, randomised, controlled trial of IL-2 in patients with current CD4 50-300 cells/mm3 and viral loads <10,000 copies/mL. The study is fully enrolled with 1,970 patients participating from across 142 sites in 11 countries. Patients were scheduled to receive 4.5 MIU IL-2 BID subcutaneous every eight weeks for six cycles. Data presented at the 9th EACS conference focused on the CD4 response in individuals who received IL-2. At entry, patients had a median CD4 count of 201 cells/mm3 (interquartile range (IQR) 150-252 cells/mm3). The median nadir CD4 count was just 60 (IQR 24-108) cells/mm3. For the 449 patients for whom data are available at one year, the median increase in CD4 count was 123 cells/mm3. Increases were more substantial in patients with higher baseline counts (142 vs 98 cells/mm3 for patient with baseline counts of >200 cells vs baseline counts of 50-199 cells/mm3); and for patients who received more cycles (139 vs 80 cells for six cycles vs <3 cycles).

The data certainly indicate that even in individuals with low CD4 counts meaningful rises in CD4 cell numbers can be achieved. The study will now continue looking at clinical events to see whether these substantial rises in CD4 numbers converted into a reduction in the number of clinical events in patients who received IL-2 relative to the control population in this study of individuals who have not received IL-2.

Levy Y, Mitsuyasu R, Tambusi G, et al. CD4 count increases in patients with CD4 counts of 50-300 treated with intermittent IL-2: immunologic results from the Study of IL-2 in Combination with Active Antiretroviral Therapy (SILCAAT) Trial. 9th EACS, Warsaw. 25-29 October 2003. Abstract F14/3
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