Bisher AKIL, MD

IL-2 increases CD4+ count but no clinical improvement

In Immune System on March 22, 2009 at 11:35 pm

Previous studies have suggested that adding Interleukin (IL)-2 will increase CD4+ cell count. The clinical benefit for such increase was inferred but not proven. In February 2009, during the 16th Conference on Retroviruses and Opportunistic Infections (CROI), two studies attempted to show the clinical benefit.
In the SILCAAT trial [Abstract 90bLB], 1695 patients who had CD4 counts <300 cells/mm3 while receiving antiretroviral therapy (ART) were randomized either to continue ART alone or to also receive IL-2 (4.5 million IU, delivered subcutaneously twice daily in at least 6 cycles of 5 days each, separated by 8-week intervals). The median nadir CD4 count was 60 cells/mm3, and the median entry CD4 count was 202 cells/mm3; 81% of patients had viral loads 500 copies/mL. The two treatment groups were well matched at baseline. During follow-up (median, 7.6 years), the IL-2 group averaged 57 more CD4 cells/mm3 than did the ART-alone group, but the rate of opportunistic disease or death was similar between the groups. Adverse event rates were also similar, except in the first year, when the IL-2 group had a higher rate of grade 4 events (mostly psychiatric and gastrointestinal).
The second study, ESPRIT trial, [Abstract 90aLB], had the same study design as SILCAAT, but the 4111 patients had baseline CD4 counts 300 cells/mm3, and the IL-2 was dosed differently (7.5 million IU, delivered subcutaneously twice daily in at least 3 cycles of 5 days each, separated by 8-week intervals). The overall median nadir CD4 count was 197 cells/mm3, and the mean enrollment CD4 count was 457 cells/mm3; 80% of patients had viral loads 500 copies/mL. Results were similar to those of the SILCAAT study: The IL-2 group gained more CD4 cells than did the ART-alone group (average difference, 153 cells/mm3) but did not have a lower rate of opportunistic disease or death. Again, the IL-2 group had an excess of grade 4 adverse events (this time, mostly vascular complications).
Comments: Why? usually more CD4+ cell count means better immune system and less infections, less death…etc. There is no clear answer, but there is no shortage of possibilities: maybe the cells generated are not as good as the cells one gets from ART; maybe IL-2 does something bad, maybe…etc. In the meantime, these were unexpected results _ BA

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