A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated with a reduced risk of HIV infection

Objectives: Coexpression of certain combinations of natural killer cell receptor KIR3DL1 and HLA-B alleles is associated with slower time to AIDS. The strongest protection in terms of disease outcome in KIR3DL1 homozygotes (3DL1 hmz) is coexpression of HLA-B*57andasetof KIR3DL1 genotypes (3DL1*h/*y) lacking alleles expressed at low levels on natural killer cells. We questioned whether this allele combination could also influence resistance to infection. Design: The genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed uninfected and 186 recently HIV-infected 3DL1 hmz. Results: Percentage carriers of HLA-B*57 in HIV-exposed uninfected and individuals in a primary infection cohort was 12.2 and 4.3%, respectively (P = 0.0631), whereas that of 3DL1*h/*y was similar in both populations (P = 0.221). The 3DL1*h/*y-HLA-B*57 combined genotype was more frequent in exposed uninfected individuals (12.2%) than individuals in primary infection (2.7%) (P = 0.019; odds ratio, 5.03; 95% confidence intervals, 1.38-18.3). Conclusion: Coexpression of 3DL1*h/*y and B*57, which has been associated with a reduced risk of progressing to AIDS in HIV-infected individuals also lowers the risk of HIV infection in exposed uninfected individuals. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.