The development of an effective HIV-1 vaccine to either prevent virus transmission or halt disease progression represents one of the major challenges in biomedical research. To date, 95 clinical trials of different HIV vaccine candidates have been completed, involving 26,000 volunteers. Although the specific functional ability and phenotype required of vaccine-induced cells to protect against HIV infection or limit transmission are unknown [1], efficacy trials afford the opportunity to uncover mechanisms and predictors of protection. To advance HIV vaccine development, it is essential to (1) identify the immune responses that candidate vaccines elicit based on standardized assays,(2) compare and prioritize responses between candidate regimens to guide product advancement decisions, and (3) define the protective mechanisms of viral containment. Because success in eliciting broadly neutralizing antibodies has been limited to date and because data on the importance of the cytotoxic T lymphocyte (CTL) response in controlling HIV exist, recent vaccine candidates advancing in clinical trials have been focused primarily on inducing cellular immunity. Virusspecific CD8 T cell responses are thought to play an important role in the control of natural HIV-1 infection, on the basis of the following observations:(1) the first appearance of HIV-1–specific CD8 T cell responses in primary infection coincides with the decline of peak viremia [2, 3];(2) depletion of CD8 T cells in simian immunodeficiency virus (SIV)–infected rhesus macaques results in increased viremia [4];(3) polymorphisms in HLA class I alleles restricting CD8 T cell responses are associated with differential HIV-1 disease outcome [5, 6]; and (4) HIV-1 evades virus-specific CD8 T cell–mediated immune pressure by selecting for variant epitope sequences [7, 8]. However, despite this strong evidence for the important role of CD8 T cell immunity in the control of HIV-1 infection, current assays to quantify T cell immunity by measuring antigen-specific cytokine production or cytotoxic activity have failed to correlate HIV-1 specific CD8 T cell responses with protection from infection or control of viral replication [9–10]. After HIV-1 infection of a cell and reverse transcription of the viral RNA, the viral genome is integrated into the host cell genomic DNA. Once active viral replication starts, resulting in translation of