The HLA-C04:01/KIR2D S4 gene combination and human leukocyte antigen alleles with high population frequency drive rate of HIV disease progression

Results: HLA class I alleles associated with a lack of viral control had a significantly higher population frequency than relatively protective alleles (P1⁄40.0093), in line with a rare allele advantage. HLA-A 02 : 01 and HLA-C 04 : 01 were both associated with high viral loads (P1⁄40.0313 and 0.0001, respectively) and low CD4þ cell counts (P1⁄40.0008 and 0.0087, respectively). Importantly, the association between HLAC 04 : 01 and poor viral control was not due to its linkage disequilibrium with other HLA alleles. Rather, the coexpression of its putative KIR ligand KIR2DS4f was critically linked to elevated viral loads.