Impact of HLA allele-KIR pairs on HIV clinical outcome in South Africa

Author:

Mori, Masahiko

Leitman, Ellen

Walker, Bruce

Ndung'u, Thumbi

Carrington, Mary

Goulder, Philip
Author Address

Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Department of Clinical Medicine, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States of America., HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa., Africa Health Research Institute (AHRI), Durban, South Africa., Max Planck Institute for Infection Biology, Berlin, Germany., Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States of America.,

Abstract:

Background. HLA class I contributes to HIV immune control through antigen presentation to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. In contrast to investigations of CTL, studies of NK cells in HIV control through HLA-killer immuno-globulin-like receptor (KIR) interactions remain sparse in African cohorts. Methods. Treatment-naive, chronically HIV-infected adults (N = 312) were recruited from South Africa, and the effects of HLA-KIR pairs on clinical outcome were analyzed. Results. There was no significant difference in viral load among all subjects with HLA alleles from the HLA-C1 group (P = .1). However, differences in HLA-C type significantly influenced viremia among 247 KIR2DL3 positives (P = .04), suggesting that specific HLA-KIR interactions contribute to immune control. Higher viral load (P = .02) and lower CD4(+) T-cell counts (P = .008) were observed in subjects with HLA-C*16:01(+)KIR2DL3(+). Longitudinal analysis showed more rapid progression to AIDS among HLAC*16:01(+)KIR2DL3(+) subjects (adjusted hazard ratio 1.9, P = .03) than those without this genotype, independent of CD4+ T-cell count and viral load. Conclusions. These results highlight the existence of unique anti-HIV innate immunity within distinct populations and the contribution of KIR on NK cells and some CTLs to the well-described HLA-mediated impact on HIV disease progression.

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