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Abstract
Associations of HLA-DRB alleles with resistance/susceptibility to HIV-1 infection in the Pumwani sex worker cohort
P. Lacap1, J. Huntington (co-presentor)1, M. Luo2, J. Ndinya-Achola3, S. Njenga3, J.B. Bwayo3, S. Ramdahin4, T. Bielawny1, J. Rutherford4, L. Slaney4, J. Kimani3, C. Wachihi3, E.N. Ngugi5, F.A. Plummer6
Background: A group of sex workers in the Pumwani Sex Worker Cohort remain HIV-1 PCR negative and IgG antibody negative despite heavy exposure to HIV-1 through sex work. Previous studies showed that this resistance to HIV-1 infection is associated with several HLA alleles, HIV-specific CD8+ and CD4+ T cell responses as well as mucosal neutralizing antibody to HIV-1. The strong CD4+ T cell responses of HIV resistant women to p24 antigen indicate that HLA class II antigens are important. To comprehensively study the effect of DRB alleles and haplotypes on the resistance/susceptibility to HIV-1 infection in the Pumwani Sex Worker Cohort we conducted a high-resolution sequence-based DRB typing of 1083 women.
Methods: DNA was isolated from whole blood or PBLs. HLA DRB genes were amplified and sequenced. A two-step sequence-based method was used for DRB typing. Allele and haplotype frequencies were determined using PyPop 32-0.6.0. Data analysis was conducted with SPSS 13.0 for Windows.
Results: Three DRB1 alleles were significantly associated with resistance to HIV-1 infection: DRB1*010201 (OR, 2.13; 95% CI, 1.31-3.47; P = 0.002), DRB1*1102 (OR, 1.91; CI95%, 1.21-3.01; P = 0.005) and DRB1*130201 (OR, 1.51; CI95%, 1.00-2.28; P = 0.047). Two corresponding DRB1-DRB3 haplotypes were also significantly associated with HIV-1 resistance: DRB1*1102-DRB3*020201 (OR, 1.85; CI95%, 1.15-2.97; P = 0.010) and DRB1*130201-DRB3*030101 (OR, 1.55; CI95%, 1.03-2.35; P = 0.037). DRB1*1503 (OR, 0.603; CI95%, 0.37-1.00; P = 0.046) and its corresponding haplotype, DRB1*1503-DRB5*010101(OR, 0.571; CI95%, 0.35-0.94; P = 0.027), were significantly associated with susceptibility to HIV-1 infection.
Conclusions: We identified two DRB alleles, DRB1*1102 and DRB1*130201, as well as two DRB1-DRB3 haplotypes, DRB1*1102-DRB3*020201 and DRB1*130201-DRB3*030101 that are associated with resistance to HIV-1 infection. Our findings provide additional support that HLA class II-specific CD4+ responses are important in resistance to HIV-1 infection.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
MOPE0017
Suggested Citation
"P.Lacap, et al.
Associations of HLA-DRB alleles with resistance/susceptibility to HIV-1 infection in the Pumwani sex worker cohort.
:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
MOPE0017"
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