Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-079 Trials)

Objective: Interleukin (IL)-2 therapy leads to significant CD4 cell increases in HIV-infected patients. Since phase III trials are ongoing, studies supporting the long-term feasibility of this strategy are needed. Methods: We studied the long-term outcomes of 131 patients treated with IL-2 in two studies initiated either before (ANRS 048) or following (ANRS 079) the advent of HAART. Results: At the last assessment (median follow-up 3.4 years), these patients experienced again of 428 cells/mu l and a decrease in plasma HIV RNA to 1.70 log(10) copies/ml. In both studies, high CD4 cell counts were maintained with a median of ten 5-day cycles of subcutaneous IL-2. Median time since the last cycle was 2 years. At last assessment, 59% of 048 patients maintained a non-HAART regimen. Detailed analysis at week 170 showed that median CD4 cell counts were 856 (048) and 964 (079) cells/mu l. This corresponded to a gain from baseline of 515 (048) and 627 (079) cells/mu l. The median viral load decreases from baseline and corresponded to 1.70 (048) and 1.88 (079) log, 0 copies/ml. Comparisons across the studies showed that CD4 gains and viral load changes were similar whether HAART or non-HAART was used. The frequency of cycling, but not CD4 cell counts, viral loads or antiviral regimen at baseline, was predictive of long-term CD4 gain (P=0.03). Conclusion: Altogether, these observations support IL-2 as a long-term therapeutic strategy in HIV infection. (C) 2007 Lippincott Williams & Wilkins.