Human leukocyte antigen-DQ alleles and haplotypes and their associations with resistance and susceptibility to HIV-1 infection

Objectives: To determine the association of DQ antigens with resistance and susceptibility to HIV-1. Design: Despite repeated exposure to HIV-1, a subset of women in the Pumwani Sex Worker cohort established in Nairobi, Kenya in 1985 have remained HIV-1 negative for at least 3 years and are classified as resistant. Differential susceptibility to HIV-1 infection is associated with HIV-1 specific CD4(+) and CD8(+) T cell responses. As human leukocyte antigen-DQ antigens present viral peptides to CD4(+) cells, we genotyped human leukocyte antigen -DQ alleles for 978 women enrolled in the cohort and performed cross-sectional and longitudinal analyses to identify associations of human leukocyte antigen -DQ with resistance/susceptibility to HIV-1. Methods: DQA1 and DQB1 were genotyped using taxonomy-based sequence analysis. SPSS 13.0 was used to determine associations of DQ alleles/haplotypes with HIV-1 resistance, susceptibility, and seroconversion rates. Results: Several DQB1 alleles and DQ haplotypes were associated with resistance to HIV-1 infection. These included DQB1*050301 (P= 0.055, Odds Ratio = 12.77, 95% Confidence Interval= 1.44-112), DQB1*0603 and DQB1*0609 (P=0.037, Odds Ratio= 3.25, 95% Confidence Interval = 1.12-9.47), and DQA1*010201-DQBI*0603 0603 (P=0.044, Odds Ratio= 17.33, 95% Confidence Interval= 1.79-168). Conversely, DQB1*0602 (P= 0.048, Odds Ratio= 0.68, 95% Confidence Interval= 0.44-1.05) and DQA1*010201-DQB1*0602 (P=0.039, Odds Ratio=0.64, 95% Confidence Interval =0.41-1.03) were overrepresented in the HIV-1 infected population. DQA1*0504-DQB1*0201, DQA1*010201-DQB1*0201, DQA1*0402-DQB1*0402 and DQA1*0402-DQB1*030101 genotypes were only found in HIV-1 positive subjects (Odds Ratio= 0.30-0.31, 95% Confidence Interval =0.03-3.70), and these women seroconverted rapidly. The associations of these DQ alleles and haplotypes with resistance and susceptibility to HIV-1 were independent of the previously reported human leukocyte antigen-DRB*01, human leukocyte antigen A2/6802, and human leukocyte antigen-A*2301. Conclusion: The associations of DQ alleles and haplotypes with resistance and susceptibility to HIV-1 emphasize the importance of human leukocyte antigen-DQ and CD4 in anti-HIV-1 immunity. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.