Abstract
Variation in the host response to infection by pathogens including HIV-1 may be conferred by polymorphic genetic factors such as HLA and killer immunoglobulin-like receptors (KIR) genes. Here, we examined KIR and HLA genotype effects on pretreatment viral load, rate of CD4+ T-cell decline and progression to AIDS among adult HIV-1-infected patients within the Western Australian HIV Study Cohort. In this study, carriage of KIR genes within the ‘B’ haplotype (eg KIR2DS2) was specifically associated with a more rapid CD4+ T-cell decline over time and progression to AIDS. In contrast, KIR gene repertoire had no effect on pretreatment viral load while selected HLA alleles (eg HLA-B*5701, HLA-B*2705) demonstrated significant protective effects on viremia. Furthermore, interactions between specific HLA and KIR genes did appear to influence HIV disease progression. The results suggest that host genetic variation within the HLA and KIR gene complexes have clinically relevant effects on the course of HIV-1/AIDS, acting independently as well as synergistically to modify disease progression at multiple levels.
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Acknowledgements
We acknowledge the support of the Western Australian HIV cohort and the staff at the Department of Clinical Immunology and Biochemical Genetics (DCIBG), Royal Perth Hospital, Western Australia. We thank Dr Elizabeth Freitas, Filipa Carvalho and Annette Patterson for their contribution. SG is supported by a Healy Fellowship from the Raine Medical Research Foundation.DD and EM equally contributed to the work described in this manuscript. Part of this work was supported by the National Health and Medical Research Council Grant Number 237412.
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Gaudieri, S., DeSantis, D., McKinnon, E. et al. Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression. Genes Immun 6, 683–690 (2005). https://doi.org/10.1038/sj.gene.6364256
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DOI: https://doi.org/10.1038/sj.gene.6364256
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