A Randomised Trial of Subcutaneous Intermittent Interleukin-2 without Antiretroviral Therapy in HIV-Infected Patients: The UK--Vanguard Study.

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. Design and Setting: This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom. Participants: Participants were 36 antiretroviral treatment naïve HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm³. Interventions: 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. Outcome Measures: 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/mm³ for those assigned IL-2 (both dose groups combined) and 13 cells/mm³ for control participants (95% CI for difference, 51.3-181.2 cells/mm³; p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm³ (p = 0.008) and 128.4 cells/mm³ (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 log10 copies/ ml) and control (0.09 log10 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/mm³, 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. [ABSTRACT FROM AUTHOR]