Natural Killer Cells That Respond to Human Immunodeficiency Virus Type 1 (HIV-1) Peptides Are Associated with Control of HIV-1 Infection

Human immunodeficiency virus (HIV)-specific natural killer (CD3(-) cells), CD4, and CD8 T cellular responses were determined in 79 HIV-1-infected women in response to HIV-1 peptide pools (Gag, Pol, Nef, Reg, and Env) with use of a whole-blood intracellular cytokine staining assay that measures interferon-gamma and/or interleukin-2. HIV-specific CD3(-) cell responses to any region (Env and Reg predominantly targeted) were associated with lower viral load (P = .031) and higher CD4 T cell count (P = .015). Env-specific CD3(-) cell responses were stronger in women who had both Gag CD4 and CD8 T cell responses and, in turn, was associated with lower viral load (P = .005). CD3(-) cell responders had significantly higher representation of CD4 T cell responses to Env and Reg (P = .012 and P = .015, respectively) and higher magnitudes of CD4 T cell responses (P = .017 and P = .037, respectively) than did nonresponders. Peptide-specific natural killer cells are associated with markers of less severe disease progression among HIV-1-infected women (lower viral load and higher CD4 T cell count) and with stronger HIV-specific T cell responses.