Update on Interleukin-2 clinical trials

In March/April 2009 we reported on the results of the SILCAAT and ESPRIT interleukin-2 (IL-2) trials. These trials found no clinical benefit from using IL-2 with ART. At IAS2009, Abdel Babiker presented a pooled data analysis of the two studies. [1]

In addition, Jorge Tavel presented the findings of the STALWART IL-2 trial, which was unblinded early following the negative results of the SILCAAT and ESPRIT trials. [2]

In the combined ESPRIT and SILCAAT analysis, 2,920 patients were randomised to ART plus IL-2 and 2,886 took ART without IL-2. There were 39,902 person-years, 550 primary events and 381 deaths. The pooled analysis showed no statistically significant differences in opportunistic disease or death between ART + IL-2 compared to ART alone (HR=0.93; 95%CI: 0.78-1.09; p=0.33). For opportunistic diseases alone, HR=0.88 (95%CI: 0.68-1.13; p=0.32). For all cause mortality alone, HR=0.96 (95%CI: 0.78-1.17; p=0.68). There were however significantly more adverse events in the IL-2 arms (HR=1.19; 95%CI: 1.06-1.33;p=0.002).

Babiker explained that this suggests that cells induced by IL-2 have no role in host defense or that the negative effects of IL-2 neutralised any improvements in host defense conferred by IL-2.

The STALWART trial had three arms, IL-2 alone (IL-2; n=89), IL-2 with short-course ART at the time of IL-2 cycles (IL-2+; n=87) and a control group that using neither IL-2 nor ART (n=91). The cycled ART regimen involved 14 days of ART preceding the first IL-2 cycle (which lasted five days) followed by two days of ART. This was the same in subsequent IL-2 cycles, except the pre-IL-2 ART regimen was shortened to three days.

As with ESPRIT and SILCAAT, there was a significant rise in CD4 counts for people on both IL-2 arms (+114 on IL-2; +110 on IL-2+; -21.8 in the control; p<0.001 for both arms compared to control). A greater number of patients assigned to the control subsequently started ART.

Both IL-2 groups were associated with a significantly greater number of grade 3 or 4 adverse events. Five patients in each of the IL-2 groups experienced an opportunistic disease or died versus one patient in the control. People in the IL-2 groups started continuous ART less frequently probably because of their IL-2 elevated CD4 counts.

Comment

These results confirm the lack of clinical benefit from IL-2 in the setting of HAART, and no apparent functional advantage from IL-2-induced increases in CD4 count.

CD4 counts in patients who have used IL-2 may therefore be artificially high, and HAART should perhaps be started in these patients at higher CD4 counts than recommended in treatment guidelines.