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CD8⁺ T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8⁺ T cell response, with limited bystander activation of non-HIV memory CD8⁺ T cells. HIV-specific CD8⁺ T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8⁺ T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8⁺ T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine …