Background: There is renewed interest in the use of immunotherapy as an adjunct to antiretrovirals (ART) in the treatment of HIV disease. Most work has been performed on interleukin-2 (IL-2). There is considerable evidence from numerous phase II studies that intermittent dosing of subcutaneous IL-2 plus antiretroviral therapy (ART) produces a sustainable rise in the CD4(+) T-lymphocyte count which exceeds that which can be achieved using ART alone, without any adverse effect on plasma HIV RNA. However, the immunological competency and therefore clinical impact of this expanded CD4(+) T cell pool is yet to be established; this question is the focus of two large clinical end-point studies, ESPRIT and SILCAAT.
Objective: Prior to the establishment of ESPRIT, four 'Vanguard' studies were undertaken; the UK Vanguard examined the safety and virological/immunological aspects of intermittent subcutaneous IL-2 without the use of ART in HIV-1 ART naïve patients with a baseline CD4(+) T cell count of > or = 350cells/mm(3).
Design: The UK Vanguard was an open-label, randomised study comparing subcutaneous (s/c) IL-2 at either 4.5MIU or 7.5MIU q12h for 5 days every 8 weeks versus no therapy in HIV-1-infected individuals. Primary endpoints included mean area under the curve change from baseline CD4(+) T cell count and plasma log HIV-RNA.
Results: Thirty six subjects were enrolled into the three arms of the UK Vanguard study. Results showed significant differences in the area under the curve (AUC) change from baseline CD4(+) T cell count (P = 0.001) and changes in mean absolute CD4(+) T cell count (P = 0.04) and no significant difference in mean AUC change from baseline plasma HIV-RNA (P = 0.48) at 24 weeks between the IL-2 and control arms respectively. The significance of these results and those from other studies on the use of IL-2 in HIV disease are discussed.