Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV.

Background: Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4 + T cells may persist following viral rebound has not been fully investigated. Methods: Patients with CD4 + T cells 500/μl or more and HIV RNA less than 50 copies/ ml were randomized to continue antiretroviral therapy (ART) either alone (n=67) or combined with three IL-2 cycles (n= 8 1; 6 million units) twice daily for 5 days at weeks 0, 8, and 16 before stopping ART (week 24). Patients were followed up to 168 weeks. Results: At week 24, median CD4 + T-cell counts were 1198 and 703 cells/μl in the I L-2 and control groups, respectively (P < 0.001). At week 72, 27% (IL-2 group) and 45% (control group; P=0.03) of patients were in failure (defined as no interruption of ART at week 24, CD4 drop below 350 cells/μl or ART resumption). After week 24, a biphasic decline (before and after week 32) of CD4 was noted -106 and -7 cells/μl per month in controls and -234 and -17 in IL-2 group (all P≤ 0.0001). At week 96, IL-2-expanded CD4 + CD25 + T cells remained higher than in the control group (26 vs. 16%, P= 0.006). Conclusion: In IL-2-treated patients, CD4 + CD25 + T cells persisting despite viral replication allow a longer period of ART interruption.