Background: ESPRIT is an open-label, randomized, controlled trial to determine if (SC) IL-2 therapy + combination antiretroviral therapy (ART) vs ART alone reduces risk of AIDS or death in patients with baseline CD4 ³300 c/µL.  IL-2 was given BID in 3 5-day cycles q8 weeks, with more cycles if CD4 did not reach goal of ³2xbaseline or ³1000 copies/µL. We examined baseline characteristics of patients by CD4 change after 3 cycles of IL-2.

Methods: So far, 219 patients have completed 3 cycles of IL2 therapy starting at 7.5 MIU BID and have month 8 CD4 data. Patients were grouped in tertiles based on month-8 CD4 change from baseline: <246 copies/µL increase (n=72); 246-484 increase (n=73); and >484 increase (n=74).  Demographics, injecting drug use history, co-infection with hepatitis B/C, nadir and baseline CD4, HIV RNA, HIV disease stage, body mass index, and duration of ART (dual nucleosides or HAART) were compared across tertiles by analysis of variance and <greek>chi</greek>² tests.  Multiple regression analysis with change in CD4 from baseline to month 8 as the outcome was performed using the above baseline factors.

Results: In univariate analyses of baseline factors, nadir CD4 (p=0.003), duration of ART (p=0.01), and duration of HAART among those 158 (72%) patients prescribed HAART (p=0.005) varied significantly by tertile of CD4 change (from smallest to largest CD4 change tertile: nadir CD4 253 vs 318 vs 349; duration of ART 64 vs 50 vs 45 months; duration of HAART 37 vs 29 vs 26 months). In multivariate analysis, nadir CD4 was significantly associated with CD4 change at month 8, with a 100-copies/µL higher nadir having a 41-cell greater CD4 increase (p=0.001); and a greater CD4 increase (180 copies/µL more) was found among patients with <1 year HAART compared to other patients (p=0.01).

Conclusion: These preliminary data indicate that the CD4 increase after 3 cycles of IL-2 given with ART is substantial (median increase 389 cells/mm³) and consistent across demographic characteristics as well as HIV stage and baseline levels of CD4 and HIV RNA. Duration and type of ART (combination nucleoside vs HAART) both appear to be associated with CD4 response. Among these patients with baseline CD4³300copies/µL, nadir CD4 was the strongest predictor of response in multivariate analyses.