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Volume 6 Supplement 3

AIDS Vaccine 2009

P08-04. The role of class I HLA-B and HLA-Cw in disease progression and maternal-infant HIV-1 transmission in a South African population

Background

Human leukocyte antigens play an integral role in the cytotoxic T-cell pathway and serve as ligands for natural killer cell receptors. We have investigated the role of two HLA class I genes on disease progression and maternal-infant HIV-1 transmission using 222 South African mother-infant pairs recruited as part of a mother-to-infant HIV-1 transmission study.

Methods

High resolution genotyping of HLA class I B and Cw loci was performed using a sequence-based typing strategy and alleles were collapsed to a four-digit assignment for purpose of analysis.

Results

B*5802 and Cw*0602 were significantly associated with high viral load (VL) (P = 0.038 and P = 0.017 respectively) and low CD4 count (P < 0.001 and P = 0.005 respectively). These two alleles are in linkage disequilibrium (D' = 1.00; P < 0.001) and the most prevalent haplotype amongst Black South Africans (f = 9.94%). The B*5802-Cw*0602 haplotype was also significantly associated with low CD4 count (P = 0.001) and showed a trend with high VL (P = 0.073). Furthermore, B*4501 showed a trend with high VL (P = 0.086) and low CD4 count (P = 0.062). B*4201 was significantly associated with low VL (P = 0.045) and another prevalent haplotype, B*4201-Cw*1701 (f = 9.65%), was significantly associated with low VL (P = 0.049). The Cw allotype groups (C1&C2) showed no significant association with markers of disease severity, whereas, contrary to other studies, Bw4/Bw4 homozygosity was significantly associated with high VL (P = 0.038) and low CD4 count (P = 0.015).B*0801 showed a trend (P = 0.064) of lower representation amongst infected infants compared to exposed uninfected infants. Transmitting mothers had significantly higher representation of B*1402 (P = 0.034) and a trend of lower representation of B*4201 (P = 0.082) compared to non-transmitting mothers. No Cw* alleles or allotype groups showed significant association with HIV-1 transmission.

Conclusion

This study highlights the different roles played by HLA in disease progression and maternal-infant HIV-1 transmission and also serves as a basis for future work that will study the role of KIR-HLA in the same contexts.

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Correspondence to M Paximadis.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Paximadis, M., Minevich, G., Winchester, R. et al. P08-04. The role of class I HLA-B and HLA-Cw in disease progression and maternal-infant HIV-1 transmission in a South African population. Retrovirology 6, P112 (2009). https://doi.org/10.1186/1742-4690-6-S3-P112

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Keywords

  • Viral Load
  • Human Leukocyte Antigen
  • High Viral Load
  • Lower Representation
  • South African Population