Phase 1 trial of a single dose of recombinant human interleukin-12 in human immunodeficiency virus-infected patients with 100-500 CD4 cells/microL.
A phase 1 dose-escalation trial of a single subcutaneous dose of recombinant human (rh) interleukin (IL)-12 was conducted in medically stable human immunodeficiency virus (HIV)-infected patients with 100-500/microL 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 rhIL-12 at 1000 ng/kg had severe adverse events. Dose-related increases in serum interferon-gamma occurred after rhIL-12 administration at doses > or =30 ng/kg. There was no effect of rhIL-12 on plasma HIV RNA or absolute CD4(+) T cell counts. However, dose-related increases in absolute CD8(+) T and NK cells were observed in subjects assigned to rhIL-12 doses of 30-300 ng/kg. Single rhIL-12 doses of 30-300 ng/kg were well tolerated and had biologic activity that could potentially be of benefit in the treatment of HIV disease or its complications.
Jacobson
M A
MA
Positive Health Program, Department of Medicine, University of California, San Francisco, CA 94110, USA. mjacobson@php.ucsf.edu
Hardy
D
D
Connick
E
E
Watson
J
J
DeBruin
M
M
D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000009:adverse effects* / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D044469:Racial Groups; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D012367:RNA, Viral; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma