Subcutaneous interleukin-2 in combination with anti-retroviral therapy fortreatment of HIV-1-infected subjects

A total of 11 HIV-1 positive patients, with CD4+ cell counts between 200 an d 500/mu l, who were in stable anti-retroviral therapy, were treated with s ubcutaneous recombinant human IL-2 thrice weekly administered on an out-pat ient basis in a dose-escalating manner. Subcutaneous IL-2 was well tolerate d and associated with only mild to moderate constitutional symptoms and loc al inflammation at the injection site. CD4+ fell count increased from 404 /- 48/mu l at baseline to 639 +/- 88/mu l at week 6, with proportionate inc reases in naive cells and memory cells. Increased doses of IL-2 were then n eeded to sustain the number of CD4+ cells. After discontinuation of IL-2 tr eatment, CD4+ cell count returned to baseline Levels. IL-2 induced a reduct ion in the percentage of CD8 + CD38 + and CD8 + HLA - DR + cells, an increa se in the fraction of CD8 + CD25 + and CD8 + CD122 +, and an elevation in t he number of NK-cells. IL-2 did not induce any clinically significant chang e in plasma HIV-RNA. In conclusion, IL-2 can safely be administered subcuta neously on an out-patient basis to HIV-infected individuals with CD4 + cell counts from 200/mu l to 500/mu l and with some improvement in immunologica l abnormalities. Continuous therapy, however, seems to result in the develo pment of tachyphylaxia.