Inefficient immune recovery under highly active antiretroviral therapy (HAART) represents a clinical issue. Twenty-seven of 121 HIV+ naïve patients became immunological nonresponders (INRs) and 55 introduced therapy late [very late treated (VLT)]. INR displayed older age, lower CD4(+) cell counts, down-regulation of CD127(+)CD4(+) and higher apoptotic CD95(+)CD8(+). VLT also showed higher activated CD38(+)CD8(+)%. The only factor associated with INR status was CD127(+)CD4(+)%. INR showed lower baseline interleukin (IL)-7 levels and a reduced expression of IL-7R (CD127(+)) on naïve and memory T-cells, reaching significance in memory CD127(+)CD45(+)R0(+)CD4(+). These results suggest a possible role for the IL-7/IL-7R system in the pathogenesis of poor immunological recovery during HAART.