346   Meta-Analysis of the CD4 Cell Response to 3 Doses of Subcutaneous Interleukin-2 (scIL-2) Across 3 Vanguard Studies.

R. Arduino*, E. Nannini, M. Rodriguez-Barradas, S. Schrader, M. Losso, K. Ruxrungtham, M. Allende, S. Emery, L. Fosdick, J. Tavel, R. Davey, and H. C. Lane for the Esprit Vanguard Group and the Esprit Executive Committee.
Univ. of Texas-Houston.

Background:Three identically designed Vanguard studies showed that scIL-2 given bid in 5-day cycles q8 weeks for 3 cycles significantly increases the CD4 cell count in HIV-1-infected subjects on antiretroviral therapy (ART) and CD4 >350 cells/mm³. This meta-analysis summarizes the impact of 3 doses of scIL-2 on the CD4 cell count to determine the dose that provides the optimal CD4 response.

Methods:Results from 218 pts randomized by 11 sites (73, 73, and 72 pts in Houston, Argentina and Thailand, respectively) were pooled for each dose comparison: 72 were randomly allocated to 1.5 MIU (N = 36) or control (N = 36); 72 to 4.5 MIU (N = 36) or control (N = 36); and 74 to 7.5 MIU (N = 37) or control (N = 37). Baseline CD4 averaged 514 cells/mm³(nadir 339); 44% pts had viral load <500 copies/mL; 25% pts were taking NRTIs only and 75% were on a regimen with an NNRTI or PI; average age was 35 years and 36% were female.

Results:At 6 months after 3 cycles, the average CD4 differences between IL-2 and control (± SE) doses were 74+44; 347+61; and 645+101, respectively. After 6 months, additional cycles of IL-2 could be given as needed and dose was increased to a maximum of 7.5 MIU. Between 6 and 12 months, for pts assigned the 1.5, 4.5 and 7.5 MIU doses, 78%, 39% and 35% received at least one additional dose and 13 (36%), 5 (14%), and 3 (8%) required 2 or 3 more cycles, respectively. 20 (55%) pts in 1.5 MIU and 20 (55%) in 4.5 MIU dose group increased IL-2 to 6.0 or 7.5 MIU; while in the 7.5 MIU dose group, 1 (3%) is currently receiving 4.5 MIU dose and 4 (11%) 6.0 MIU dose. At 12 months, the CD4 difference between IL-2 and control was 325+35 (p < 0.0001). The CD4 differences between IL-2 and controls were 188+52; 370+66; and 436+64, for 1.5, 4.5, and 7.5 MIU respectively. Currently, of the 109 patients assigned IL-2, 51 (47%) are receiving 7.5 MIU, 25 (23%) 6.0 MIU, 26 (24%) 4.5 MIU, and 7 (6%) 3.0 MIU or less.

Conclusions:scIL-2 promotes a significant dose-dependent CD4 cell count increase in HIV-1-infected individuals on ART. This analysis supports initial use of 7.5 MIU dose.