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 efficacyof combined therapy with polyethylene glycolated (PEG) interleukin (IL)-Z 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 × 10⁶ IU/m² and reversible encephalopathy in 1 subject at 3 × 10⁶ 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 3 were entered into a chronic dosing phase. PEG IL-2 was given at 14-day intervals at doses of 10⁶ IU/m² for 8 weeks and 3 × 10⁶ 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 3, to determine whether increased lymphocyte numbers will translate into improved clinical outcome.