Honduras HIV cohort: HLA class I and CCR5-Δ32 profiles and their associations with HIV disease outcome

Abstract

ABSTRACT Human leukocyte antigen (HLA) polymorphisms represent the strongest genetic modifier of HIV disease progression. Diverse HLA distributions can lead to distinct HIV control landscapes at the population level. We aimed to describe HLA allele and haplotype frequencies (linkage disequilibrium, LD), CCR5-Δ32 frequency, and the impact of these variants on HIV disease outcome. HLA class I loci were typed at 4-digit resolution, and CCR5 variants were determined in 402 HIV clade B-infected, antiretroviral treatment-naïve individuals from Honduras. HLA LD was assessed using Fisher’s exact test. Using univariable and multivariable analyses, we evaluated HLA associations with HIV plasma viral load (pVL) and CD4 counts. We did not find any effect on HIV control between CCR5 genotypes. The previously defined HLA associations were found to be B*57:01/03, B*42:01, A*25:01, and C*12:03 (protective) and B*53:01 and A*68:01 (risk). Consistent with our previous research in a Mesoamerican HIV cohort, Amerindian B*35:12 was associated with poor HIV control. Other HLA-HIV associations not previously described were C*03:04 and B*08:01, which were associated with higher pVL. Overall, this first report highlights the immunogenetic uniqueness of the Honduras population that expresses Amerindian, Caucasian, and African HLA subtypes. These findings not only support this cohort as ideal for identifying HLA correlates of HIV control but also may improve future research regarding allotransplantation and disease association. IMPORTANCE We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

Keywords

• HLA allele frequencies
• HLA haplotype structures
• HLA linkage disequilibrium
• HLA-HIV disease associations
• Honduran Mestizos
• Latin America