Efforts aimed at restoring robust immune responses limiting therapeutically human immunodeficiency virus (HIV)-1 replication are warranted. We report that vaccination with dendritic cells (DC) generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (P = 0.009); ii) the frequency of functional T cells (producing at least 2 cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (P = 0.002) and from 0.26 to 0.35% (P = 0.005) for CD4+ and CD8+ T cells, respectively; and iii) the breadth of cytokines secreted by peripheral blood mononuclear cells (PBMCs) upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17 and IL-13. Fifty percent of patients experienced a peak of viral load (VL) 1 log10 lower than the other half following antiviral treatment interruption. An inverse correlation was found between the peak of VL and the frequency of polyfunctional CD4+ T cells (P = 0.007), production of IL-2 (P = 0.006,), IFN-γ (P = 0.01), IL-21 (P = 0.006) and IL-13 (P = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection.This article is protected by copyright. All rights reserved