Background The correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analysed and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status. Methods Two groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations: long-term nonprogresssors (LTNPs, n = 20) and advanced progressors (APs, CD4 count <500 cells/μl, n = 34). Nef-specific CD8 T-cell responses were studied by interferon-γ ELISpot assay against 3 pools of HIV-Nef peptides. Results Nef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs (670 SFC/106 peripheral blood mononuclear cells vs 1107 SFC/106 peripheral blood mononuclear cells, P = 0.255). Further comparisons showed that there were also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load (r = –0.397, P = 0.020) and positively with CD4 count (r = 0.364, P = 0.034) in group APs. Conclusion These data suggest that different correlation patterns between Nef-specific CD8 T-cell responses and disease progression exist in LTNPs and APs. Although a negative association was observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV-1 infection. Background The correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analyzes and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status. Methods Two groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations: long-term nonprogressors (LTNPs, n = 20) and advanced progressors (APs, CD4 count <500 cells / Nef-specific CD8 T-cell responses were studied by interferon-γ ELISpot assay against 3 pools of HIV-Nef peptides. Results Nef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs (670 SFC / 106 peripheral blood mononuclear cells vs 1107 SFC / 106 peripheral blood mononuclear cells, P = 0.255). Further comparisons showed that there we re also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load (r = -0.397, P = 0.020) and positively with CD4 count (r = 0.364, Conclusion These data suggest that the different correlation patterns between Nef-specific CD8 T-cell responses and disease progression in concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV-1 infection.