Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection

Certain human leukocyte antigens, by presenting conserved immunogenic epito pes for T cell recognition, may, in part, account for the observed differen ces in human immunodeficiency virus type 1 (HIV-1) susceptibility. To deter mine whether HLA polymorphism influences HIV-1 susceptibility, a longitudin al cohort of highly HIV-1-exposed female sex workers based in Nairobi, Keny a, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/ 6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [ CI], 0.27-0.72; P = .0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addi tion, resistance to HIV-1 infection was independently associated with HLA D RB1*01 (IRR, 0.22; 95% CT, 0.06-0.60; P = .0003), which suggests that anti- HIV-1 class II restricted CD4 effector mechanisms may play an important rol e in protecting against viral challenge, These data provide further evidenc e that resistance to HIV-1 infection in this cohere of sex workers is immun ologically mediated.