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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-07. HLA-B1302 is associated with viral control in clade CRF01_AE HIV-1 infection in Thailand

Background

Little is known about the role of different HLA class I alleles in the control of HIV-1 CRF01_AE infections, which dominate in South and Southeast Asia, or the CD8+ T-cell responses that might be mediating this effect.

Methods

We studied a cohort of 250 chronically HIV-1 infected, HAART naïve individuals in Bangkok, Thailand. Viral load and CD4 data were collected for all individuals as well as 4-digit HLA typing and viral sequences. A comprehensive screen of CD8+ T-cell responses was conducted using an IFN-gamma ELISpot assay and overlapping clade AE-specific peptides (OLP) spanning the entire HIV-1 proteome.

Results

Of HLA alleles previously associated with control, namely B5701, B27, B51 and B1302, only HLA-B1302 was associated with significantly lower viral loads (n = 14, p = 0.029, q = 0.115) and with HIV-1 'controllers' (VL<2000/ml; p = 0.016). In examining which CD8 responses might be mediating this protective effect, we found that the majority of frequently targeted OLPs in HLA-B1302+ subjects were located in Gag and Pol (7 of top 9 responses; avg. 753 spot forming cells (SFC/106 PBMC). In addition, we found frequent (avg. 58% recognition) and strong (avg. 872 SFC) responses against 3 of 6 previously described clade C HLA-B1302 epitopes in Gag and Pol (Gag-VV9, Pol-GI9, and Gag-RI9), versus infrequent (avg. 12% recognition) and weak (avg. 316 SFC) responses to the other described epitopes in Pol, Nef and Gag (Pol-RI10, Nef-GI11, Gag-GI11). In analyzing for CTL escape mutations in the 3 targeted epitopes or OLPs in Gag, we found no evidence of viral escape.

Conclusion

HLA-B1302 is correlated with virus control in CRF01_AE infection and appears to predominantly target highly conserved regions of Gag and Pol. These data extend the observation that maintenance of CD8+ T-cell responses against highly conserved regions of HIV may also be critical to long-term control of CRF01_AE.

Author information

Correspondence to U Hempel.

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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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Hempel, U., Buranapraditkun, S., Chatkulkawin, P. et al. P16-07. HLA-B1302 is associated with viral control in clade CRF01_AE HIV-1 infection in Thailand. Retrovirology 6, P236 (2009). https://doi.org/10.1186/1742-4690-6-S3-P236

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Keywords

  • Viral Load
  • Viral Sequence
  • ELISpot Assay
  • Viral Control
  • Escape Mutation