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ASSOCIATIONS OF EXTENDED HLA-CLASS II HAPLOTYPES WITH RESISTANCE OR SUSCEPTIBILITY TO HIV-1 INFECTION IN THE PUMWANI SEX WORKER COHORT
P Lacap1, M Luo1, R Hardie1, J Huntington1, C Semeniuk1, E Knight1, B Bruneau1, J Kimani2, C Wachihi2, E Ngugi2, F Plummer1,2
1Winnipeg, MB; 2Nairobi, Kenya
Objectives: To characterize the distribution of extended HLA class II haplotypes and assess their role in resistance and susceptibility to HIV-1 infection in the Pumwani Sex worker Cohort.
Design: A subset of women in the Pumwani Sex worker Cohort, established in 1985 in Nairobi, Kenya, remain HIV-1 negative despite frequent exposure to the virus through active sex work. Specific CD4+ T-cell responses, influenced by HLA class II, have been shown to associate with resistance to HIV-1 infection, demonstrating the importance of HLA class II based anti-HIV-1 immunity. Seven hundred and thirty six women, of whom 119 were resistant to HIV-1 infection, were genotyped for DQA1, DQB1, DPA1, DPB1, and DRB1 using a high-resolution sequence-based method. Extended haplotype frequencies were determined using PyPop32-0.6.0. Statistical analysis was conducted with SPSS-13.0. Haplotypes with five or more copies in the population were tested for associations with resistance or susceptibility to HIV-1 infection by chi-square analysis and the Fisher's exact test.
Results: Forty unique DQA1-DQB1-DPA1-DPB1-DRB1 haplotypes were present at more than five copies in the population. The three most frequent haplotypes were DQA1*040101-DQB1*0602-DPA1*010301-DPB1*020102-DRB1*1503 (2.89%), DQA1*010201-DQB1*0602-DPA1*010301-DPB1*020102-DRB1*1503 (2.55%), and DQA1*050101-DQB1*030101-DPA1*0301-DPB1*0402-DRB1*030201 (2.14%). The haplotype DQA1*050101-DQB1*030101-DPA1*020202-DPB1*010101-DRB1*1102 (P=0.010; OR:5.119; CI95%:1.535-17.069) was associated with resistance to infection. The haplotypes DQA1*010201-DQB1*0602-DPA1*010301-DPB1*040101-DRB1*1503 (P=0.019; OR:Infinite; CI95%:Infinite) and DQA1*010201-DQB1*0602-DPA1*0301-DPB1*0402-DRB1*1503 (P=0.005; OR:Infinite; CI95%:Infinite) were only found in HIV-1 positive women and were associated with susceptibility to infection.
Conclusions: The association of these extended HLA class II haplotypes with resistance or susceptibility to HIV-1 infection further emphasizes the importance of HLA class II specific CD4+ T cell responses against HIV-1. The results complement current knowledge on HLA class II single locus associations with resistance or susceptibility to HIV-1 infection.