1. ¹Centre for Clinical Immunology and Biomedical Statistics, Murdoch University and Royal Perth Hospital, Western Australia, Australia
2. ²Centre for Forensic Science, School of Anatomy and Human Biology, University of Western Australia, Western Australia, Australia
3. ³Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Western Australia, Australia
4. ⁴School of Surgery and Pathology, University of Western Australia, Western Australia, Australia
5. ⁵Mathematics and Statistics, Murdoch University, Western Australia, Australia

Correspondence: Professor FT Christiansen, Centre for Clinical Immunology and Biochemical Genetics, 2nd level North Block, Royal Perth Hospital, Wellington Street, Perth, Western Australia 6000, Australia. E-mail: Frank.Christiansen@health.wa.gov.au

Received 2 May 2005; Revised 19 July 2005; Accepted 19 July 2005; Published online 25 August 2005.

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.