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Natural killer (NK) cells are regulated by interactions between polymorphic killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA). Genotypic combinations of  KIR3DS1/L1  and  HLA Bw4-80I  were previously shown to influence HIV-1 disease progression, however other  KIR  genes have not been well studied. In this study, we analyzed the influence of all activating and inhibitory KIR, in association with the known HLA inhibitory KIR ligands, on markers of disease progression in a West African population of therapy-naïve HIV-1 infected subjects. We observed a significant association between carriage of a  group B KIR  haplotype and lower CD4+ T cell counts, with an additional effect for  KIR3DS1  within the frame of this haplotype. In contrast, we found that individuals carrying genes for the inhibitory KIR ligands  HLA-Bw4  as well as  HLA-C1  showed significantly higher CD4+ T cell counts. These associations were independent from the viral load and from individual HIV-1 protective HLA alleles. Our data suggest that  group B KIR  haplotypes and lack of specific inhibitory KIR ligand genes, genotypes considered to favor NK cell activation, are predictive of HIV-1 disease progression.

Low CD4+ T Cell Counts among African HIV-1 Infected Subjects with Group B KIR Haplotypes in the Absence of Specific Inhibitory KIR Ligands