Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women

Background: Killer-cell Immunoglobulin-like Receptors(KIR) interact with Human Leukocyte Antigen(HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. Methods: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54months (IQR 31-69) until 2014. Results: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44log10 copies/ml;SE = 0.18;p = 0.03) and higher CD4+ T-cell counts(+80 cells/μl;SE = 42;p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. Conclusions: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.