The HLA A2/6802 Supertype Is Associated with Reduced Risk of Perinatal Human Immunodeficiency Virus Type 1 Transmission

Abstract

Certain HLAs may, in part, account for differences in human immunodeficiency virus type 1 (HIV-1) susceptibility by presenting conserved immunogenic epitopes for T cell recognition. The HLA supertype A2/6802 is associated with decreased susceptibility to HIV-1 among sex workers. The alleles in this supertype present the same HIV-1 peptide epitopes for T cell recognition in some cases. This study sought to determine whether the HLA A2/6802 supertype influenced HIV-1 transmission in a prospective cohort of HIV-1-infected mothers and children in Kenya. Decreased perinatal HIV-1 infection risk was strongly associated with possession of a functional cluster of related HLA alleles, called the A2/6802 supertype (odds ratio, 0.12; 95% confidence interval, 0.03-0.54; P=.006). This effect was independent of the protective effect of maternal-child HLA discordance. These data provide further evidence that HLA supertypes are associated with differential susceptibility to HIV-1 transmission.

Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

“…Recognition of HLA-B*57 (specifically and exclusively, B*57031) as the single most favorable marker in Zambians, despite LD patterns that differ between this and all other cohorts, highlights B*57 itself rather than its haplotypic lineages as broadly capable of suppressing HIV-1 RNA to a relatively low level during the early stages of infection (44). B*5701-and B*5703-mediated immunodominant responses to conserved HIV-1 Gag epitopes have been documented in African-American adolescents (P. Goepfert (30,35) and that of A23 with increased transmission of HIV-1A in Kenyans (39,40). Two other comparisons are also worth mentioning: the association of Cw*16 on the B*45-Cw*16 haplotype with high VL here was consistent with its overrepresentation in rapid progressors in the GRIV cohort (21), whereas higher VL in Zambians carrying B*14-Cw*08 and A*23-B*14 contrasted with the associations of B*14 and Cw*08 with a favorable prognosis of disease progression reported elsewhere (21,41).…”

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

“…Infants expressing HLA A*02 were approximately 50% less likely to become HIV-1 infected before month 1 (RR = 0.55; 95% CI 0.3-0.9), an observation that is consistent with previous reports that also did not adjust for maternal viral load. 7 We did not observe significant protection against HIV-1 acquisition for A*02 in the analysis that adjusted for the effect of maternal immunosuppression and viral load on vertical transmission risk (Table 2). Future studies focusing on HLAs A*02 and A*29 may clarify their contribution to mother-to-child HIV-1 transmission and disease progression.…”

“…In an African breast-feeding cohort, the A2 supertype, a group of functionally related HLA subtypes, was associated with protection against infant HIV-1 infection during the first 6 months but not against later transmission through continued breast milk exposure. 7 The relationship between the A2 supertype and risk of vertical transmission was independent of the protective effect of HLA discordance between mother and child. 6,8 We examined associations between mother-to-child HIV-1 transmission and frequently expressed HLA alleles in a Kenyan perinatal cohort.…”

Structures of HLA-A*1101 Complexed with Immunodominant Nonamer and Decamer HIV-1 Epitopes Clearly Reveal the Presence of a Middle, Secondary Anchor Residue

“…Because CD8 ϩ CTL responses are restricted by polymorphic gene products of the MHC region, it is not surprising that certain class I HLA alleles have been associated, at levels that are statistically significant, with resistance to HIV-1 infection in several cohorts of highly exposed, persistently seronegative (HEPS) 3 individuals (9,(12)(13)(14). For example, a significant increase of the class I HLA-A*1101 allele has been observed in cohorts of highly exposed female sex workers from Northern Thailand who have been persistently HIV-1 seronegative, but are seropositive for other sexually transmitted diseases (9,15,16).…”