HIV-specific CD8⁺ T cells are prone to undergo apoptosis, and this may affect their ability to control HIV infection. Because CD8-mediated immune responses play a key role in controlling HIV infection, enhancing the survival and effector function of HIV-specific CD8⁺ T cells may augment their ability to control HIV virus. We show here that interleukin 15 (IL-15) potently inhibits spontaneous and CD95/Fas-induced apoptosis of HIV-specific CD8⁺ T cells. IL-15 inhibits apoptosis in both CD45RA⁻CD62L⁻ and CD45RA⁺CD62L⁻ effector memory subpopulations of these cells. Furthermore, IL-15 greatly enhances the survival of HIV-specific CD8⁺ T cells in long-term cultures. Finally, IL-15 directly enhances activation, interferon γ (IFNγ) production, and direct ex vivo cytotoxicity of HIV-specific CD8⁺ T cells. Thus, IL-15 potently enhances the survival and effector function of HIV-specific CD8⁺ T cells and, therefore, may prove useful in augmenting the antiviral function of these cells.