IL-2 induced increases in CD4 counts are blunted by use of prednisone
Simon Collins, HIV i-Base
Early results from the large international ESPRIT study presented to the IAS conference this summer confirmed the ability of several courses of IL-2 to dramatically increase CD4 counts. However, IL-2 is associated with difficult side effects during the five-day administration periods including moderate to severe fatigue, myalgia and fever in up to 90% of subjects.
These symptoms are thought to be proinflammatory responses related to elevations in tumour-necrosis facto-alpha (TNF-alpha) and IL-6 that occur with IL-2 treatment. As corticosteroids inhibit production of TNF-alpha, a small pilot study looked at whether prednisone could reduce the side effects without reducing CD4 increases.
Dr Jorge Tavel and colleagues from NIAID randomised 19 patients to one of four treatment groups (A-D): IL-2 + placebo (A), IL-2 + prednisone (B), prednisone alone (C) and placebo alone (D). Five patients were in each arm except the placebo arm, which had four patients. IL-2 was dosed at 7.5 MIU sc BID for each five day cycle, with cycles repeated every two months. Prednisone was dosed at 0.5mg/kg/day orally for seven days every two months, coinciding with the administration of IL-2.
Increases in CD4 count were 452, 110, 27 and 135 in groups A, B, C and D respectively. All subjects in group A showed significant CD4 increases, but concomitant use of prednisone blunted or in some cases prevented this in subjects in group B.
Although higher toxicity was reported in group A compared to B the researchers question whether these differences were significant. No difference in fatigue or dose reductions of IL-2 were reported between the groups A and B, although temperature was 0.4°C lower in those patients receiving prednisone.
Although prednisone decreased levels of proinflammatory cytokines during IL-2 cycles, these responses appear to be critical to IL-2 induced CD4 increases.
The authors conclude that IL-2 dose reduction in combination with use of nonsteroidal agents, is the best approach to manage toxicity and maximise response.
Tavel JA, Sereti I, Walker RE et al. A randomised, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus. J Infect Dis. 2003 Aug 15;188(4):531-6.