We studied HIV-1 clade C Gag-specific T-cell responses in five HIV-infected Ethiopians with a relatively slow (< 15 cells/microl per year) and five with a fast (> 45 cells/microl per year) CD4 T-cell decline longitudinally. Six study subjects had T-cell responses directed to one or more HIV-1 Gag peptides. The persistence of strong and broad anti-Gag cytotoxic T-lymphocyte responses was associated with a slow rate of CD4 T-cell decline and with human leukocyte antigen alleles from the B27 supertype.