Immunomodulators as adjunctive therapy for HIV-1 infection

Background. There is renewed interest in the use of immunotherapy as an adj unct to antiretrovirals (ART) in the treatment of HIV disease. Most work ha s been performed on interleukin-2 (IL-2). There is considerable evidence fr om 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 alon e, without any adverse effect on plasma HIV RNA. However, the immunological competency and therefore clinical impact of this expanded CD4(+) T cell po ol is yet to be established; this question is the focus of two large clinic al end-point studies, ESPRIT and SILCAAT. Objective: Prior to the establish ment of ESPRIT, four 'Vanguard' studies were undertaken; the UK Vanguard ex amined the safety and virological/immunological aspects of intermittent sub cutaneous IL-2 without the use of ART in HIV-1 ART naive patients with a ba seline CD4(+) T cell count of greater than or equal to 350cells/mm(3). Desi gn: The UK Vanguard was an open-label, randomised study comparing subcutane ous (s/c) IL-2 at either 4.5MIU or 7.5MIU q12h for 5 days every 8 weeks ver sus no therapy in HIV-1-infected individuals. Primary endpoints included me an 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 arm s of the UK Vanguard study. Results showed significant differences in the a rea under the curve (AUC) change from baseline CD4(+) T cell count (P = 0.0 01) and changes in mean absolute CD4(+) T cell count (P = 0.04) and no sign ificant difference in mean AUC change from baseline plasma HIV-RNA (P = 0.4 8) at 24 weeks between the IL-2 and control arms respectively. The signific ance of these results and those from other studies on the use of IL-2 in HI V disease are discussed. (C) 2001 Elsevier Science B.V. All rights reserved .