Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

Abstract

Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P ‫؍‬ 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P ‫؍‬ 0.02) or B*5802-Cw*0602 (P ‫؍‬ 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P ‫؍‬ 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P ‫؍‬ 0.06) and rapid (P ‫؍‬ 0.003) disease progression, respectively. In neither population were B*1516-

Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

“…B58s (POR, 0.33; 95% CI, 0.21 to 0.52) was associated with control that was heavily determined by B*57 alleles (POR, 0.11; 95% CI, 0.05 to 0.22). However, neither the strong protective effect observed elsewhere for B*5801 (22,27) nor the strong deleterious effect observed elsewhere for B*5802 (22,23,27) was observed in our study.…”

“…Associations between supertypes and HIV-1 outcomes have been demonstrated in previous studies of Caucasians with clade B infection (34,44) and of native Africans with clade A or C infection (23,28). Caucasians in one study showed an unfavorable effect of B7s and a favorable effect of B58s on HIV-1 control (44); in another study, Caucasians with the relatively infrequent B58s, B27s, and B62s supertypes showed enhanced CTL responses, while the more frequent B7s and B44s supertypes were associated with diminished CTL responses (34).…”

“…Previous work has detected associations between the HLA class I supertypes and HIV-1 outcomes for Caucasians with clade B infections (34,44) and for native Africans with clade A or C infections (23,28). We are unaware of studies among African Americans in the context of clade B HIV-1 infection or of any systematic attempt to tease apart the independent contributions of supertypes and their individual class I alleles to HIV-1 outcomes.…”

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

“…13 This association was not observed in healthy controls carrying the A*02 allele, indicating that the lower count may be related to a locus in LD with the A*02 allele. We identified one published report 14 of an association between the B*5802 allele and higher viral load in HIV-1 subtype C-infected Zambians, although the B*5801-Cw*03 haplotype was associated with lower viral load. Furthermore, an association between the B*58 allele and higher T-cell response in vertically-HIVinfected AA children (predominately females) has been reported.…”

Clade-Specific Evolution Mediated by HLA-B*57/5801 in Human Immunodeficiency Virus Type 1 Clade A1 p24

“…In contrast to other clades (including clade D), HLA-B*5801 does not appear to place selection pressure on clade A1 TW10. A previous study in Rwanda similarly showed that in clade A1, HLA-B*5703 but not HLA-B*5801 was associated with lower HIV viral loads (30). Therefore, HLA-B*5801 was associated with neither protection nor selection in clade A1 TW10.…”