It has long been postulated that while CD8 lymphocytes are capable of suppressing human immunodeficiency virus (HIV)-1 replication it is unlikely that the viral reservoirs once formed can be cleared. Our previous studies demonstrate that co-immunizing cynomologous macaques with a simian/human immunodeficiency virus (SHIV) DNA-based vaccines induces a strong cellular immune response that is able to suppress viral replication. We further demonstrated that interleukin (IL)-12 could significantly enhance the vaccine specific CD8 lymphocyte response. In this manuscript cynomologous macaques were vaccinated with a SHIV DNA-based vaccine co-delivered with IL-12. The macaques were then challenged with SHIV89.6p. Two years post-immunization and viral challenge we transiently depleted CD8(+) T cells. Plasma viral load increased, demonstrating the central role of CD8(+) T cells in viral suppression yet an inability to clear the viral reservoirs. Furthermore, in the data presented here, we found a higher number of IFN-gamma producing vaccine specific cells did not enhance suppression of viral replication.