Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease

Witzke O, Winterhagen T, Reinhardt W, Heemann U, Grosse-Wilde H, Kreuzfelder E, Roggendorf M, Philipp T (Departments of Medicine, Immunology and Virology, University of Essen, Germany). Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease. J Intern Med 1998; 244: 235–40. Objectives Therapy of HIV-infection using intravenous interleukin-2 (IL-2) is known to be effective in terms of increasing CD4-counts but is associated with significant side-effects and hospitalization. However, the combination with protease-inhibitor therapy has not been tested yet. The aim of the present study was to investigate the safety and efficacy of intravenous vs. subcutaneous IL-2 regimes using 9 Mio I.U. of IL-2, in combination with protease-inhibitor therapy. Design All patients were treated with a combination of two reverse transcriptase inhibitors and a protease-inhibitor prior to IL-2 administration for at least 6 weeks. Ten patients were assigned to the intravenous IL-2 group (group A), 10 to the subcutaneous group (group B). Results In both treatment groups, CD4 count significantly increased shortly after the end of therapy (group A: 223% over baseline [day 7]; group B: 264% over baseline [day 7]). During the follow-up CD4 counts slowly decreased thereafter but remained above baseline 3 months following IL-2 treatment. The CD8 lymphocytes showed a similar but less pronounced pattern with a maximum at day 7 (group A: 116% over baseline, group B: 158% over baseline) and reached baseline earlier in the follow-up-period. Altogether the CD4/CD8-ratio was elevated through long periods on follow-up. Throughout follow-up, there were no apparent changes in viral load during IL-2 therapy in either groups. IL-2 therapy was administered for a mean time of 4.2 ± 0.1 days in the intra-venous group and of 4.8 ± 0.1 days in the subcutaneous group until therapy was terminated at day 5 or due to side-effects. Only 1/10 patients completed the 5-day course of intravenous therapy in contrast to 6/10 in the subcutaneous group. Conclusions Subcutaneous interleukin-2 using 9 Mio IU day−1 in combination with protease-inhibitors showed equal efficacy as intravenous therapy and was associated with less side-effects.