ObjectiveA Phase I study of subcutaneous recombinant interleukin-2 (rlL-2).DesignSixteen patients with advanced HIV infection receiving 600–1200mg zidovudine per day were divided into three groups, which received sequentially 0.2 x106, 0.7x106or 2x106units/m2per day of rlL-2 subcutaneously for 5 consecutive days.SettingFive-day admission to an academic tertiary care hospital.Patients, participantsSixteen unblinded, non-randomized volunteers.InterventionsSubcutaneous rlL-2.Main outcome measuresTolerance, toxicity, hematologic, immunologic and antiviral responses.ResultsrlL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rlL-2 administration, with rebound within 48 h after rlL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rlL-2 receptor levels increased transiently during and immediately following rlL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rlL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden.ConclusionsSubcutaneous rlL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.