7th Conference - Abstract 341

Effects of Combined Treatment with Interleukin-2 (IL-2) and an Inactivated gp120-Depleted HIV-1 Immunogen (REMUNE) on Immune Reconstitution in HAART-Treated, HIV-1-Infected Individuals

G. HARDY*¹, N. IMAMI¹, A. SULLIVAN², J. WILSON¹, C. BURTON¹, R. MOSS³, B. GAZZARD², and F. GOTCH¹. ¹Imperial Coll. Sch. of Med. and ²Chelsea and Westminster Hosp., London, UK; and ³Immune Response Corp., San Diego, CA

Treatment with HAART does not diminish latent HIV-1 reservoirs and simultaneously fails to reconstitute virus-specific T cell responses in HIV-1 chronically infected individuals. Boosting the anti-viral effector mechanisms of the immune system in addition to activation of the latent T-cell reservoirs may enhance the decay of residual virus and/or improve the suppression of viral activity by HAART. In order to study this a randomised, phase I study of treatment with interleukin-2 in combination with therapeutic vaccination (REMUNE) has been established. Forty patients are treated for 16 weeks with HAART, two nucleoside analogues and at least one protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI). On the basis that viral loads had fallen below detectable limits and CD4⁺ T cell counts reached at least 300 cells/ml blood patients were randomised to one of four arms: A) HAART alone; B) HAART plus IL-2 S/C 5x10⁶ m/ml bid for 5 days every four weeks for three cycles; C) HAART plus IL-2 as above plus REMUNE vaccine 100mg I/M every three months four times; D) HAART plus REMUNE as above.
HAART alone is insufficient to allow reconstitution of HIV-1-specific responses and does not lead to continuous decay of residual cellular HIV-1 DNA. IL-2 with or without the addition of REMUNE is able to induce profound increases in CD4⁺ T cell counts and CD16⁺ NK cell counts in a proportion of these patients. Similarly treatment with IL-2 accelerates the decay of HIV-1 DNA, in some cases significantly reducing detectable levels following the 3 cycles. REMUNE alone induced significant in vitro HIV-1-specific CD4⁺ T cell responses after at least three doses. The addition of IL-2 therapy to REMUNE inoculation reduced the number of vaccine doses required to achieve this effect in some patients.

Key Words: HAART, IL-2, Remune