The distribution of alleles in HIV-1 infected Japanese was similar to that of the general Japanese population described above (data not shown). We then compared the level of pVL in terms of presence or absence of individual class I alleles (Table 1), and found that five alleles (HLA-A20, B07, B54, Cw01 PD-0332991 supplier and Cw15) were associated with lower or

larger pVL, (P < 0.05 by Fisher's exact probability test). However, after determining q-values (20) none of the associations remained significant, indicating that there are no strongly protective or detrimental alleles in this unique Asian population. Notably, in this cross-sectional analysis, expression of HLA-B51, which is the third most beneficial allele after B57 and B27 in Caucasians (7, 22), proved to be not at all protective in Japan; likewise, HLA-A11, A26 and Cw14, which have also been reported to be protective

in the USA in a study which controlled for ethnicity (7), did not show any protective effects in Japanese, either. Taken together, these results indicate that alleles which have protective effects in a given population do not necessarily behave similarly in other populations. An HLA supertype is defined as a group of class I alleles sharing a similar peptide binding motif, thereby being able to present the same CTL epitopes (23). Some HLA class I supertypes have been reported to be ALK inhibitor clinical trial associated with pVL in the USA: (B7s with larger pVL, and B27s/B58s with lower pVL) (24). We looked for such associations in the Japanese population by classifying alleles observed in our cohort into eight supertypes according to the literature (i.e., A1s, A2s, A3s, A24s, B7s, B27s, B44s, B62s) (23), and found that there were no significant associations between level of pVL and expression of particular class I supertypes in the Japanese population (data not shown). This finding may be due to the Japanese lacking HLA-B27/B57, which are major contributors to the protective supertypes in the USA (24). We further assessed the

impact on pVL of the Bw4/Bw6 motif of HLA class I molecules, which are known to act as ligands of KIR on natural killer cells and to modulate their activity (25, 26). Homozygosity for Bw6 motif has been reported to be associated with rapid disease progression, Amrubicin whereas the subtype of Bw4, which is carried by various alleles including HLA-B27/B57, is associated with slow disease progression (27, 28). However, there was no difference in the level of pVL between Bw4 and Bw6 homozygotes in the Japanese population (median: 26 000 vs. 20 500 RNA copies/ml, P= 0.976, Fig. 2), indicating that the findings reported from the USA cannot reliably be extended to other populations. In the cross-sectional analyses, we did not find any associations between the level of pVL and expression of individual class I alleles, supertypes or Bw motifs in this unique Asian population.