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5th International AIDS Society Conference on HIV Pathogenesis and TreatmentCape Town - July 19 - 22, 2009 |
THE IMPACTS OF HLA CLASS I ALLELES ON HIV-1 PLASMA VIRUS LOADS IN A UNIQUE ASIAN POPULATION WITH A NARROW SPECTRUM OF HLA, AND THEIR CHANGES AT THE POPULATION LEVEL OVER TIME
IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOPDA103
M. Koga
1, A. Kawana-Tachikawa1, T. Odawara1, D. Heckerman2, T. Miura1, A. Iwamoto1
1Institute of Medical Science,University of Tokyo, Tokyo, Japan, 2Microsoft Research, Redmond, United States
BACKGROUND: HLA class I types have differential impacts on the level of plasma virus loads (pVLs) and disease outcome of HIV-1 infection, probably being mediated by CTL responses. However, the accumulation of CTL escape mutations at population level has been described (Furutsuki T et al. J Virol. 2004 Aug;78(16):8437-45), suggesting that some HLA alleles might be losing the protective effects as the epidemic continues. Here, we analyzed the impact of individual HLA alleles on pVLs in a unique Asian population that has a narrow HLA distribution, thereby is easy for CTL escape mutations to accumulate in.
METHODS: HLA class I genotypes were determined from the 141 untreated HIV-1 infected Japanese individuals diagnosed from 1995-2007, and pVLs from asymptomatic phase were measured by Roche Amplicore. The associations between pVLs and expression of HLA alleles were analyzed using appropriate statistics.
RESULTS: The Japanese population has a much narrower spectrum of HLA class I alleles (total 28 alleles with >1% allelic-frequency) compared to those in Caucasians in the U.S. (total: 46 alleles); and is intriguingly lacking HLA-B27/B57 that are the most protective in the Caucasians. However, several protective alleles in the Caucasians including the 3rd protective HLA-B51 (O'Brien SJ et al. Trends Mol Med. 2001 Sep;7(9):379-81), were commonly seen in this population (A11:10.4%, A26:11.55%, B51:8.6% and Cw14:12.7%). The cross-sectional analyses revealed no significant associations between any individual alleles and pVLs. Nevertheless, we observed a clear trend that the B51+Japanese diagnosed before 2001 had lower pVLs than those diagnosed after 2005 (median: 5150 vs 41500 RNA copies/ml, p=0.08), whereas no differences were observed for the other protective alleles between the periods.
CONCLUSION: These results indicate that HLA alleles that are protective against HIV-1 infection in a given population, are not necessarily beneficial in the distinct population; and importantly, some alleles are likely losing their protective effects at population level as the epidemic continues.
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2009-07-22
MOPDA103
Poster Discussion: MOPDA1 - HLA Pathogen Interactions
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