title: Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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/microL at screening and a stable HIV viral load received low-dose IL-2 (1.2 million IU [MIU]/m 2 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/microL in the IL-2 group compared to 19.93 cells/microL 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Quest Clinical Research, San Francisco, CA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Lalezari
authors.forename: J A
authors.initials: JA
authors.lastname: Beal
authors.forename: P J
authors.initials: PJ
authors.lastname: Ruane
authors.forename: C J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: E L
authors.initials: EL
authors.lastname: Jacobson
authors.forename: D
authors.initials: D
authors.lastname: Sundin
authors.forename: W P
authors.initials: WP
authors.lastname: Leong
authors.forename: S P
authors.initials: SP
authors.lastname: Raffanti
authors.forename: D A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: R D
authors.initials: RD
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Keiser
authors.forename: S R
authors.initials: SR
authors.lastname: Schrader
authors.forename: J C
authors.initials: JC
authors.lastname: Goodgame
authors.forename: C R
authors.initials: CR
authors.lastname: Steinhart
authors.forename: R L
authors.initials: RL
authors.lastname: Murphy
authors.forename: M J
authors.initials: MJ
authors.lastname: Wolin
authors.forename: K A
authors.initials: KA
authors.lastname: Smith
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D007376:Interleukin-2