344   Effect of Subcutaneous (SC) IL-2 Therapy Combined with HAART in HIV-Infected Patients. Results of the ANRS 079 Randomized Trial.

Y. Levy*¹, C. Capitant², A. S. Lascaux¹, C. Durier², C. Michon³, L. Weiss⁴, E. Oksenhendler⁵, J. A. Gastaut⁶, C. Goujard⁷, C. Rouzioux⁸, J. P. Aboulker², J. F. Delfraissy⁷, and the ANRS 079 Study Group.
¹Hosp. Henri Mondor, Creteil;²INSERM, Villejuif;³Hosp. Louis Mourier, Colombes;⁴Hosp. Broussais, Paris;⁵Hosp. Saint-Louis, Paris;⁶Inst. Paoli Calmettes, Marseille;⁷Hosp. Bicetre, Kremlin-Bicetre;⁸Hosp. Necker, Paris; and⁹ANRS, Paris, France.

Background:Our objective was to determine the immunological and virological efficacy of SC IL-2 combined with HAART compared to HAART alone.

Methods:118 outpatients with baseline (BL) 200—550 CD4 cells/mm³

without prior AIDS events and naive to antiretrovirals or naive to PI, were randomized to start a new combination: D4T + 3TC + Indinavir either alone (HAART) or combined with SC IL-2 cycles (5 MIU, bid, 5 days) every 4 weeks (w) for 3 cycles and every 8w for 7 following cycles.

Results:Planned interim analysis of the first 80 pts who completed the study (w74) was done in an intent-to-treat approach. The median (range) increase from BL in CD4 cell counts/mm³(337 (200—549)) was +865 (-62— 3,031) in IL-2 arm and +240 (-237—588) in controls (p < 10^-4). At w16, 68.5% of pts who received 3 IL-2 cycles compared to 7.5% treated with HAART had a 80% increase of CD4 counts (p < 10^-4). At w74 this percentage was 89% compared to 44% (HAART arm) (p < 10^-4). Mean (SD) plasma HIV RNA log₁₀cp/ml, decreased from 3.86 (1.05) (IL-2 arm) and 4.04 (0.91) (HAART) to 1.87 (0.57) in both arms. At w74, the percentage of pts with plasma viral load <50 cp/ml was high in both arms (86—90%) (p = 0.7) and the mean proviral DNA log₁₀cp/10⁶PBMC was 2.58 (IL-2 arm) and 2.43 (HAART) (p = 0.3). Common toxic effects of IL-2 led to reduction of the mean (SD) dose administered per cycle from 48.5 (3.6) at cycle 1 to 43 (10) at cycle 10.

Conclusions:Compared to HAART alone, intermediate doses of IL-2 combined with HAART allowed a greater increase in CD4 cells and a similar control in HIV replication with limited dose reductions.