Background:Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients.Methods:Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200–550 × 106cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 × 106IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74.Results:CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 × 106cells/l, respectively;P< 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P< 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P< 0.0001) and natural killer cells (P< 0.001). In a logistic regression analysis, odds of being responders to recall antigensin vitrowas 8.5-fold higher in IL-2 recipients (P= 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively;P= 0.01).Conclusions:The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.