Human leukocyte antigen class I supertypes and HIV-1 control in African Americans.
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.
Lazaryan
Aleksandr
A
University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
Song
Wei
W
Lobashevsky
Elena
E
Tang
Jianming
J
Shrestha
Sadeep
S
Zhang
Kui
K
Gardner
Lytt I
LI
McNicholl
Janet M
JM
Wilson
Craig M
CM
Klein
Robert S
RS
Rompalo
Anne
A
Mayer
Kenneth
K
Sobel
Jack
J
Kaslow
Richard A
RA
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
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I