The development of HIV-1-specific CD8⁺ T-cell responses during acute HIV-1 infection is associated with a dramatic decline in HIV-1 replication and the resolution of the acute retroviral syndrome. These HIV-1-specific CD8⁺ T cells typically target a small number of viral epitopes in a distinct hierarchical order, and high-level viremia in chronic progressive infection leads to broadly diversified HIV-1-specific CD8⁺ T-cell responses with a less clear immunodominance pattern. It is argued here that the specific hierarchical pattern of immune responses in acute HIV-1 infection is the result of a tightly regulated process that, among other factors, is critically impacted by the kinetics of viral protein expression, the HLA class I background of the infected individual and the autologous sequence of the infecting virus.