We examined CD8+ T lymphocyte characteristics in Rwandan women who have survived HIV-1 subtype A infection for 8-13 years without antiretroviral therapy. HIV-1 subtype A gag-specific IFN-gamma expressing CD8+ T lymphocytes were detectable in PBMC from 5 of 7 women and there was a strong positive association (r = 0.9262; p < 0.001) between these cells and plasma viral load. CD8+ T cells of these HIV-positive women produced more RANTES and MIP-1beta than cells from HIV-negative donors. However, extremely low levels of perforin (0.88 +/- 0.93%) were produced by CD8+ T lymphocytes from the infected women compared with HIV-negative controls (42.86 +/- 11.0%; p < 0.001). The percentages of CD8+ CD45RA+ perforin+ and CD8+ CD45RA+ CD27-lymphocytes were also much lower in the HIV-infected women compared with HIV-negative controls. Therefore, the inability of CD8+ T cells to control HIV may, in part, be dependent on insufficient generation of effectors from HIV-specific CD8+ T cells. Also, the lack of perforin in CD8+ T cells is linked with persistent CD27 expression, suggesting impaired maturation and impairment in cytolytic activity in chronic HIV-1 infection.