Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not able to achieve their desired response. An alternative strategy to the antibody approach is the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were previously demonstrated to play an important role in the control of simian immunodeficiency virus (SIV), the HIV equivalent studied in rhesus macaque monkeys. Additionally, other studies suggest CTLs play an important role in viral control during chronic infection. Based on this information, several groups have shifted their focus to the development of CTL-based vaccines, some of which have entered advanced clinical trials.