We report the results of the Theravac‐01 phase I trial, which was conducted to evaluate the safety and immunogenicity of a poxvirus‐based vector, NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate. NYVAC‐B vaccine was injected intra‐muscularly into ten HIV‐infected patients successfully treated with antiretroviral therapy, twice on day 0 and again at week 4. Safety and immunogenicity were monitored for 48 weeks. HIV‐specific T‐cell responses following immunization were quantitatively analyzed using an IFN‐γ ELISPOT assay and qualitatively characterized for their functional profile (including multiple cytokines secretion plus cytotoxic and proliferation capacity) by polychromatic flow cytometry. Our results indicate that the NYVAC‐B vaccine is safe and highly immunogenic, as indicated by increased HIV‐specific T‐cell responses in virtually all vaccinees. Interestingly, both an expansion of preexisting T‐cell responses, and the appearance of newly detected HIV‐specific CD4⁺ and CD8⁺ T‐cell responses were observed. Furthermore, immunization mostly induced an increase in Gag‐specific T‐cell responses. In conclusion, NYVAC‐B immunization induces broad, vigorous, and polyfunctional HIV‐specific T‐cell responses, suggesting that poxvirus‐based vaccine regimens may be instrumental in the therapeutic HIV vaccine field.