IL-2 without HAART may delay need for antiretroviral treatment

A pilot study run in the UK for the larger ESPRIT study (of IL-2 with HAART), looked at using IL-2 without background HIV treatment. Results were presented by Mike Youle in a late-breaker presentation.

IL-2 can boost CD4 counts and favourably alter immune function when used together with ARVs, and is recommended in the French treatment guidelines for anyone whose CD4 count remains below 200 after six months maximally suppressive HAART. There is a concern however that IL-2 also increases HIV-1 viral burden, if not supported by HAART. This study set out to look at whether there are benefits to using IL-2 alone, possibly as a strategy to delay using combination therapy.

36 treatment naive individuals (35 male) were randomised (1:1:1) to receive either high dose IL-2 (7.5MIU, twice daily), low dose IL-2 (4.5MIU, twice daily) or no treatment. IL-2 was given sub-cutaneously for 5 days, every 8 weeks, for 24 weeks. Subjects who received IL-2 could then continue cycles on request. Baseline CD4 and viral load (averaged from last three pre-treatment results) in the IL-2 and control group were 445 cells/mm3 and 476 cells/mm3 and 4.4 log and 4.1 log respectively. The primary endpoints for the study were mean area under the curve (AUC) change from baseline CD4 cell count and plasma log10HIV RNA.

After 24 weeks people receiving IL-2 had significantly greater increases in CD4 increases than the control group by +148cells/mm3 vs +25 c/mm3 (p=0.001). By 48 weeks this increased to +232 cells/mm3 vs +13 cells/mm3 respectively (p = 0.02). Differences between the higher and lower dose arms were not significant (p=0.39). Surprisingly, there were no significant differences between the two groups in terms of changes in viral load although the change in viral load appeared to remain one log higher than the control arm.

IL-2 is certainly associated with significant side effects – similar to having a heavy flu during the dosing week, often requiring time off work. For the remainder of each two-month side effects are rare. 3 out of 12 patients discontinued treatment from the high dose compared to only one discontinuation in the low dose arm. I person in each arm left the study before receiving IL-2.

When IL-2 is used with combination therapy the CD4 increases produced are much stronger than in this study (around 300-400 cells/mm3 over six months). However, the direction of the approach of this study was to determine if a significant benefit for people who will not or cannot use combination therapy as it is required. Delaying the initiation of ARV treatment, perhaps for several years, by maintaining CD4 count over 300, despite side effects for one in every eight weeks, is an option that some people may prefer and this approach deserves further study.