title: HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort.
abstract: Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan-Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm³). A*01 (P = 0.020), C*06:02 (P = 0.042) and C*07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320-0.790]. Conversely, A*23:01 (P = 0.004), B*07:02 (P = 0.003) and B*42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290-3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132-0.544). B*07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A*74:01 (P = 0.04/P = 0.006), B*14 (P = 0.003/P = 0.003) and B*57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B*07:02 (P = 0.020), B*15:10 (P = 0.022) and B*53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B*35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1.
authors: HIV and Human Genetics, National Microbiology Laboratory, Winnipeg, MB, Canada.
authors: T A
authors: TA
authors: Peterson
authors: J
authors: J
authors: Kimani
authors: C
authors: C
authors: Wachihi
authors: T
authors: T
authors: Bielawny
authors: L
authors: L
authors: Mendoza
authors: S
authors: S
authors: Thavaneswaran
authors: M J
authors: MJ
authors: Narayansingh
authors: T
authors: T
authors: Kariri
authors: B
authors: B
authors: Liang
authors: T B
authors: TB
authors: Ball
authors: E N
authors: EN
authors: Ngugi
authors: F A
authors: FA
authors: Plummer
authors: M
authors: M
authors: Luo
mesh_terms: D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology* / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007630:Kenya; D015810:Linkage Disequilibrium / Q000235:genetics; D015999:Multivariate Analysis; D060386:Sex Workers
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I