title: Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection.
abstract: Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, 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 addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. kmacdonald@mtsinai.on.ca.
authors.forename: K S
authors.initials: KS
authors.lastname: MacDonald
authors.forename: K R
authors.initials: KR
authors.lastname: Fowke
authors.forename: J
authors.initials: J
authors.lastname: Kimani
authors.forename: V A
authors.initials: VA
authors.lastname: Dunand
authors.forename: N J
authors.initials: NJ
authors.lastname: Nagelkerke
authors.forename: T B
authors.initials: TB
authors.lastname: Ball
authors.forename: J
authors.initials: J
authors.lastname: Oyugi
authors.forename: E
authors.initials: E
authors.lastname: Njagi
authors.forename: L K
authors.initials: LK
authors.lastname: Gaur
authors.forename: R C
authors.initials: RC
authors.lastname: Brunham
authors.forename: J
authors.initials: J
authors.lastname: Wade
authors.forename: M A
authors.initials: MA
authors.lastname: Luscher
authors.forename: P
authors.initials: P
authors.lastname: Krausa
authors.forename: S
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: E
authors.initials: E
authors.lastname: Ngugi
authors.forename: J J
authors.initials: JJ
authors.lastname: Bwayo
authors.forename: F A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D000328:Adult; D015331:Cohort Studies; D016001:Confidence Intervals; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007630:Kenya / Q000453:epidemiology; D008137:Longitudinal Studies; D008285:Major Histocompatibility Complex; D011110:Polymorphism, Genetic; D011477:Sex Work; D013997:Time Factors
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains