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: R Wood, J G Montoya, S K Kundu, D H Schwartz, T C Merigan
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 167 Issue 3 Pg. 519-25 (Mar 1993) ISSN: 0022-1899 [Print] United States
• PMID: 8095058 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Viral
• HIV Core Protein p24
• Interleukin-2
• interleukin-2, polyethylene glycol-modified
• Polyethylene Glycols
• Zidovudine

Topics

• Adult
• Analysis of Variance
• CD4-CD8 Ratio (drug effects)
• CD4-Positive T-Lymphocytes (drug effects)
• DNA, Viral (analysis)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• HIV Core Protein p24 (blood)
• HIV Infections (drug therapy, immunology)
• HIV-1
• Humans
• Infusions, Intravenous
• Interleukin-2 (adverse effects, analogs & derivatives, therapeutic use)
• Killer Cells, Lymphokine-Activated (drug effects)
• Killer Cells, Natural (drug effects)
• Leukocyte Count (drug effects)
• Middle Aged
• Polyethylene Glycols
• T-Lymphocyte Subsets (drug effects)
• Virus Replication (drug effects)
• Zidovudine (therapeutic use)