The factors accelerating the acquisition of a fully mature CD56dim CD57+ KIR+ NKG2C+ CD85j+ NKG2A− phenotype during HIV-1 infection in comparison with HIV-1-HCMV− individuals and driving a greater loss of PLZF expression in HIV-1-infected patients compared with HIV-1-uninfected HCMV-seropositive controls remain unclear. Here, KLRC2 is linked to HIV-1 infection.