In this study, we observed, in the Beijing PRIMO prospective acute HIV-1 infection cohort, early activation, proliferation capacity, and the HIV-1-specific responses of KIR3DL1-positive CD8 T cells were significantly weaker than those of KIR3DL1-negative CD8 T cells in individuals homozygous for Bw4. More interestingly, KIR3DL1-negative NK cell activation capacity was negatively related to the viral load (VL) set point and the number of HIV-1-specific KIR3DL1−CD8+ T cells responses in individuals homozygous for Bw4 during acute/early HIV-1 infection. This evidence concerns the gene KIR3DL1 and HIV-1 infection.