Phase 1 trial of a single dose of recombinant human interleukin-12, in human immunodeficiency virus-infected patients with 100-500 CD4 cells/mu L

A phase 1 dose-escalation trial of a single subcutaneous dose of recombinan t human (rh) interleukin (IL)-12 was conducted in medically stable human im munodeficiency virus (HIV)infected patients with 100-500/mu L absolute CD4( +) T lymphocytes, Subjects at each dose level were randomly assigned (3:1) to receive rhIL-12. or placebo. Among the 47 subjects enrolled, rhIL-12 was well tolerated at doses of 3-300 ng/kg, but 4 of 5 subjects who received r hIL-12 at 1000 ng/kg had severe adverse events. Dose-related increases in s erum interferon-gamma occurred after rhIL-12 administration at doses greate r than or equal to 30 ng/kg. There was no effect of rhIL-12 on plasma HIV R NA or absolute CD4(+) T cell counts. However, dose-related increases in abs olute CD8(+) T and NK cells were observed in subjects assigned to rhIL-12 d oses of 30-300 ng/kg, Single rhIL-12 doses of 30-300 ng/kg were well tolera ted and had biologic activity that could potentially be of benefit in the t reatment of HIV disease or its complications.