title: Safety and efficacy of polyethylene glycol-modified interleukin-2 and zidovudine in human immunodeficiency virus type 1 infection: a phase I/II study.
abstract: The safety and efficacy of combined therapy with polyethylene glycolated (PEG) interleukin (IL)-2 and zidovudine was assessed in 19 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects in a phase I/II open-label dose-ranging study. During courses of three weekly infusions of PEG IL-2, dose-limiting side effects were seen at 5 x 10(6) IU/m2 and reversible encephalopathy in 1 subject at 3 x 10(6) IU/m2. Significant increases were seen in CD4 cell counts (P < .01), NK cell activity (P < .05), and HIV-specific cytotoxicity (P < .01). Virologic monitoring (quantitative DNA polymerase chain reaction and p24 antigen assay) showed no evidence of increased HIV activation. Patients with CD4 cells < 200/mm3 were entered into a chronic dosing phase. PEG IL-2 was given at 14-day intervals at doses of 10(6) IU/m2 for 8 weeks and 3 x 10(6) IU/m2 for up to 16 weeks, resulting in mean CD4 cell count elevations of 16% and 33%, respectively. PEG IL-2 appears to warrant further investigation, especially in subjects with CD4 cell counts < 200/mm3, to determine whether increased lymphocyte numbers will translate into improved clinical outcome.
authors.affiliation: AIDS Clinical Trials Unit, Stanford University Medical Center, California 94305.
authors.forename: R
authors.initials: R
authors.lastname: Wood
authors.forename: J G
authors.initials: JG
authors.lastname: Montoya
authors.forename: S K
authors.initials: SK
authors.lastname: Kundu
authors.forename: D H
authors.initials: DH
authors.lastname: Schwartz
authors.forename: T C
authors.initials: TC
authors.lastname: Merigan
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D011092:Polyethylene Glycols; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D004279:DNA, Viral; D016655:HIV Core Protein p24; D007376:Interleukin-2; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols; D015215:Zidovudine