Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by CD4+ T cells. The role of Th17 during the human immunodeficiency virus (HIV)-1 infection is still unclear, but HIV-1 infection can cause a preferential depletion of Th17 cells. It has been shown that IL-15 elicits IL-17 production from human peripheral blood mononuclear cells. We studied the effect of IL-15 stimulation in vitro on IL-17 production from CD4+ mononuclear cells of HIV-infected patients. We observed that IL-15 triggers, in a dose-dependent manner, IL-17 secretion. This effect was blocked by anti-IL-15 monoclonal antibody (P=0.01). Interestingly, IL-17 production was significantly lower in patients with detectable plasma viremia when compared with successfully treated HIV-infected patients (P=0.02) and healthy controls, respectively (P<0.001). We also noticed a significant difference in IL-17 production between naïve HIV-infected patients and patients with virological failure on combined antiretroviral therapy (cART) (P=0.02). Our results suggest that IL-15 can induce IL-17 production from peripheral CD4+ mononuclear cells of HIV-infected patients. Persistent HIV plasma viremia could cause a severe perturbation of IL-17 production from CD4+ mononuclear cells. IL-17 production in HIV-infected patients could be recovered through a sustained suppression of the viral replication in the peripheral blood through cART.