title: Human leukocyte antigen class I supertypes and HIV-1 control in African Americans.
abstract: The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Lazaryan
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Elena
authors.initials: E
authors.lastname: Lobashevsky
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Lytt I
authors.initials: LI
authors.lastname: Gardner
authors.forename: Janet M
authors.initials: JM
authors.lastname: McNicholl
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Klein
authors.forename: Anne
authors.initials: A
authors.lastname: Rompalo
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mayer
authors.forename: Jack
authors.initials: J
authors.lastname: Sobel
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D002648:Child; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000208:ethnology* / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D019562:Viral Load; D055815:Young Adult
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I