Activation of NK cells is associated with HIV-1 disease progression.

The main predictor of HIV-1 disease progression is CD8(+) T cell activation, characterized by elevated expression of CD38 and HLA-DR. NK cells are also activated in viremic HIV-1-infected individuals. However, the relationship between NK cell activation and HIV-1 disease progression remains undefined. We characterized NK cell activation and its association with disease progression in treatment of naive HIV-1-infected individuals, who naturally maintained low/undetectable viremia (elite and viremic controllers), compared with progressors and AIDS subjects, and treated individuals. Our results show that CD38 expression on NK cells, predominantly in the cytotoxic CD56(dim)CD16(+) subset, is associated with HIV-1 disease progression (CD4(+) T cell count and pVL), T cell activation (percentage of CD38(+)HLA-DR(+) T cells), sCD14, inflammation, and innate immune activation. Moreover, NK cell activation is increased in HIV-1-infected subjects progressing to AIDS but not in elite and viremic controllers. ART partially reduces the proportion of activated NK cells. Furthermore, our results show that individuals, who naturally control viremia, maintain low levels of innate immune activation similar to those of uninfected controls.