We have previously demonstrated that escape mutations from CTL re

We have previously demonstrated that escape mutations from CTL restricted by HLA-A24, which is the most common allele in Japan (expressed in >70% of Japanese), has been accumulating amongst viral strains circulating in Japan, implying that individuals expressing HLA-A24 have been losing their targeting epitopes (16). Likewise, there is a report that the majority of recently-infected HLA-A02+ individuals in

the USA cannot mount CTL responses to the epitopes that had been previously recognized in HLA-A02+ individuals, CH5424802 clinical trial suggesting that escape mutations from this response have been accumulating in the USA population (29). Moreover, a recent study by Kawashima et al. has demonstrated accumulations of CTL escape mutations for various HLA class I alleles at population levels (17). However, it remains unknown how these accumulations of viral escape mutations in populations affect the course of the disease. We thought that the narrow HLA class I spectrum in the Japanese population might facilitate accumulation of CTL escape mutations, and thereby their influence on disease progression might be more evident in Japan than in other countries. We initially compared level of

pVL between individuals diagnosed in the early days of the HIV epidemic and those diagnosed in later years by stratifying the subjects according to the year of HIV diagnosis, regardless of their HLA profiles, but found no difference in the level of pVL between

find more the two phases of the epidemic (Fig. 3a). Next, we focused on HLA-A24, which is shared by over 70% of Japanese people and for which we have previously demonstrated accumulation of CTL escape mutations at the population level (16). However, no difference was observed between the A24+ Japanese diagnosed before 2001 and those diagnosed after 2005 (median: 9650 vs. 23 000 RNA copies/ml, P= 0.379, Fig. 3b). We then performed similar comparisons for the alleles considered protective in Caucasians SPTBN5 and commonly expressed in the Japanese (A11: 10.4%, A26:11.6%, B51:8.6% and Cw14:12.7% of allelic-frequency) (7, 18), and observed a trend that individuals expressing HLA-B51 and diagnosed before 2001 had substantially lower pVL than those diagnosed after 2005 (median 5150 vs. 41 500 RNA copies/ml, P= 0.08, Fig. 3c). Moreover, while HLA-B51+ persons displayed significantly lower pVL than B51 negative individuals before 2001 (median 5150 vs. 18 000 RNA copies/ml, P= 0.048), such differences were not observed between people diagnosed after 2005 (Fig. 3c). Given that Kawashima et al. have recently reported a similar trend for HLA-B51 (17), it appears evident that HLA-B51 has been losing its advantage over the other alleles.

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