Telomerase activity in HIV-1-specific CD8(+) T cells from controllers contributes to the maintenance of highly functional cytotoxic T cell responses against HIV-1. Here, we show that high expression of telomerase in controllers is associated with hypermethylation at the distal and hypomethylation at the proximal human telomerase catalytic subunit promoter, whereas HIV-1-specific CD8(+) T cells from progressors showed an inverse pattern with distal promoter hypomethylation and proximal promoter hypermethylation. These data suggest distinct epigenetic signatures in HIV-1-specific T cells in progressors and controllers.