The mechanisms underlying non-progression in HIV-1 infection are not well understood; however, this state has been associated previously with strong HIV-1-specific CD8⁺ T cell responses and the preservation of proliferative CD4⁺ T cell responses to HIV-1 antigens. Using a combination of interferon-gamma (IFN-γ) ELISpot assays and tetramer staining, the HIV-1-specific CD8⁺ T cell populations were quantified and characterized in untreated long-term HIV-1-infected non-progressors and individuals with slowly progressive disease, both in relation to CD4⁺ T cell responses, and in comparison with responses to cytomegalovirus (CMV) antigens. High levels of CD8⁺ T cell responses specific for HIV-1 or CMV were observed, but neither their frequency nor their phenotype seemed to differ between the two patient groups. Moreover, while CMV-specific CD4⁺ T cell responses were preserved in these donors, IFN-γ release by HIV-1-specific CD4⁺ T cells was generally low. These data raise questions with regard to the role played by CD8⁺ T cells in the establishment and maintenance of long-term non-progression.