Interleukin-2 (IL-2) and IL-7 are the most intriguing molecules in immune-based HIV infection treatment. An in vitro IL-2/IL-7 cross-talk due to IL-2-driven IL-7 receptor-alpha-chain (IL-7R alpha) down-modulation, potentially blocking IL-7 signalling has been described. We investigated the in vivo IL-2 effect on IL-7/IL-7R system, measuring free IL-7, and IL-7R alpha CD4 and CD8 in 12 HIV-positive patients enrolled in a randomized IL-2 trial. Compared to HAART alone, IL-2 induced a parallel expansion in total and naive CD4, TRECs and IL-7 plasma levels, with no IL-7R alpha CD4 and IL-7R alpha CD8 changes (P>0.05), suggesting that in vivo IL-2 boosts IL-7 production without down-modulating IL-7R alpha, preserving IL-7-mediated T-lymphocyte homeostatic regulation. Our data confirm the pivotal role of IL-2 and IL-7 in the regulation of T-lymphocyte homeostasis in HIV infection.