Low-Dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: A randomized controlled trial

Jacob P. Lalezari, Jeffrey A. Beal, Peter J. Ruane, Calvin J. Cohen, Elizabeth L. Jacobson, David Sundin, D. Pharm, F. Wai Ping Leong, Stephen P. Raffanti, David A. Wheeler, Roger D. Anderson, Philip Keiser, Shannon R. Schrader, C. Jeffrey Goodgame, Corklin R. Steinhart, Robert L. Murphy, Maurice J. Wolin, Kendall A. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Previous studies with intermittent interleukin-2 (IL-2) therapy using intermediate and high levels of IL-2 have demonstrated significant increases in the CD4+ T cell count in HIV-infected patients. Intermittent regimens are amenable to outpatient use, but severe adverse events are frequently experienced with intermediate- and high-dose levels of IL-2. Therefore in this study, the effect of daily, subcutaneous low-dose IL-2 therapy on safety and immunological endpoints was investigated to determine whether immunological benefit could be achieved without toxicity in HIV-infected patients also receiving highly active antiretroviral therapy (HAART). Method: A total of 115 patients were enrolled in the trial. Fifty-six asymptomatic HIV-infected patients who had CD4+ T cell counts less than 300 cells/μL at screening and a stable HIV viral load received low-dose IL-2 (1.2 million IU [MIU]/m2 beginning dose) once daily in conjunction with HAART (IL-2 group). Fifty-nine patients received HAART alone (control group). Results: A dramatic effect of IL-2 on the natural killer (NK) cell population was observed with mean increases of 156 cells/μL in the IL-2 group compared to 19.93 cells/μL in the control group (p<.001). Additionally, IL-2-treated patients experienced a statistically significant increase in the mean percentage of CD4+ T cells (3.52% increase) when compared to control patients (1.33% increase) (p<.001). The expanded CD4+ T cell population was primarily of the naive phenotype, with mean increases of 4.53% for the IL-2 group and 0.31 % for the control group (p<.001 for between-group difference). In addition, a higher proportion of IL-2-treated patients (67%) compared to control patients (33%) achieved increases of greater than 50% in the CD4+ T cell count (p = .08). Adverse events of grade 3 or grade 4 toxicity were infrequent in the current study and were substantially lower by comparison to those in studies of intermittent dose IL-2 therapy. Also, negligible changes in the HIV viral load from baseline to final measurement were observed in both groups. A trend toward a reduced number of modifications of antiretroviral therapy was apparent in the IL-2 group when compared to control patients. Conclusion: Daily, low-dose subcutaneous IL-2 therapy in conjunction with HAART is safe and well tolerated and is effective in expanding lymphocyte cell types including NK cells and naive T cells in individuals who have <300 CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalHIV Clinical Trials
Issue number3
StatePublished - 2000


  • Human immunodeficiency virus
  • Interleukin-2

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases


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