Volume 6 Supplement 3

AIDS Vaccine 2009

Open Access

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

  • U Hempel1,
  • S Buranapraditkun2,
  • P Chatkulkawin2,
  • P Pitakpolrat2,
  • LC Phillips1,
  • RL Allgaier1,
  • S Lorenzen2,
  • WH Hildebrand3,
  • T Leitner4,
  • P Matthews5,
  • P Goulder5,
  • BD Walker1,
  • K Ruxrungtham2 and
  • TM Allen1
Retrovirology20096(Suppl 3):P236

DOI: 10.1186/1742-4690-6-S3-P236

Published: 22 October 2009

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.

Authors’ Affiliations

(1)
Ragon Institute of MGH, MIT and Harvard
(2)
Vaccine and Cellular Immunology Laboratory, Chulalongkorn University
(3)
Dept. of Microbiology and Immunology, University of Oklahoma
(4)
Theoretical Biology and Biophysics, Los Alamos Laboratory
(5)
University of Oxford

Copyright

© Hempel et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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