Update on Interleukin-2 clinical trials

Nathan Geffen, i-Base and TAC

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.


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.


  1. Babiker A. An analysis of pooled data from the ESPRIT and SILCAAT studies: findings by latest CD4+ count. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 19-22 July 2009, Cape Town. Oral abstract TUAB101.
  2. Tavel J. Immunologic and virologic effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy (ART): The INSIGHT STALWART Study. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 19-22 July 2009, Cape Town. Oral abstract TUAB102.

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