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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/μ1, 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 patts 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.