title: A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study.
abstract: OBJECTIVE
  The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection.
  
  
  METHODS
  This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom.
  
  
  METHODS
  Participants were 36 antiretroviral treatment naïve HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3).
  
  
  METHODS
  Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day (12 participants) or 9 MIU/day (12 participants) or no treatment (12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk.
  
  
  METHODS
  Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis.
  
  
  RESULTS
  Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 (both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3-181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) (p = 0.008) and 128.4 cells/mm(3) (p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow-up (95% CI for difference, -0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy.
  
  
  CONCLUSIONS
  In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels.
authors.affiliation: Royal Free Centre for HIV Medicine, London, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Youle
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Lisa
authors.initials: L
authors.lastname: Fosdick
authors.forename: George
authors.initials: G
authors.lastname: Janossy
authors.forename: Clive
authors.initials: C
authors.lastname: Loveday
authors.forename: Ann
authors.initials: A
authors.lastname: Sullivan
authors.forename: Christian
authors.initials: C
authors.lastname: Herzmann
authors.forename: Handan
authors.initials: H
authors.lastname: Wand
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Tavel
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane