Background:  Individuals with KIR3DS1 in the presence of HLA-B Bw4-80I show a significant delay in HIV-1 disease progression. The role of the other KIR genes is less well studied. In this study, we analyzed the influence of inhibitory and activating KIR genes and their HLA ligands on markers of HIV-1 disease progression in a population of female sex workers (FSW) in Abidjan, Côte d'Ivoire.

Methods:  We studied 32 HIV-1-seropositive FSW attending a confidential clinic in Abidjan, Cote d'Ivoire. All subjects were therapy-naive at the time of sampling. Inhibitory and activating KIR and their known HLA class I ligand genes were molecularly typed using polymerase chain reaction (PCR) -SSP and PCR-SSO techniques, respectively. In a cross-sectional set-up, KIR genotypes and KIR/HLA gene combinations were correlated with the subjects’ first CD4⁺ T cell count and HIV-1 plasma viral load result at the clinic.

Results:  FSW with an AA KIR genotype, containing few activating KIR genes, showed a significantly higher CD4⁺ T cell count than FSW with an AB or BB KIR genotype (median values of 626 vs 332 cells/mL; p = 0.001). Independent from this, FSW who possessed HLA ligand genes for all of their inhibitory KIR genes showed a significantly higher CD4⁺ T cell count than FSW who lacked HLA ligand genes for 1 or more inhibitory KIR genes (median values of 523 vs 363 cells/mL; p = 0.036). No such associations were found with HIV-1 plasma viral load levels.

Conclusions:  The presence of an AA KIR genotype or having HLA ligand genes for all inhibitory KIR genes independently predisposes to higher CD4⁺ T cell counts among African HIV-1-seropositive FSW. These KIR/HLA genotypes are predictive for weaker natural killer (NK) cell activation and stronger NK cell inhibition, respectively, which may protect against HIV disease progression through inhibition of NK cell-mediated killing of CD4⁺ T cells.