New Associations with the HIV Predisposing and Protective Alleles of the Human Leukocyte Antigen System in a Peruvian Population

Abstract

The accurate determination of an individual’s unique human leukocyte antigen (HLA) allele holds important significance in evaluating the risk associated with autoimmune and infectious diseases, such as human immunodeficiency virus (HIV) infection. Several allelic variants within the HLA system have been linked to either increased protection or susceptibility in the context of infectious and autoimmune diseases. This study aimed to determine the frequency and association of HLA alleles between people living with HIV (PLHIV) as the case group and Peruvian individuals without HIV with high-risk behaviors of sexually transmitted diseases as the control group. Whole exome sequencing (WES) was used to determine high-resolution HLA allelotypes using the OptiType and arcas HLA tools. The HLA alleles present in HLA classes I (A, B, and C loci) and II (DPB1, DQA1, DQB1, and DRB1 loci) were determined in a cohort of 59 PLHIV (cases) and 44 individuals without HIV (controls). The most frequent HLA alleles were A*02:01, DPB1*04:02, and DQB1*03:419 at 36%, 30%, and 28% prevalence in general population. We found that C*07:01 (p = 0.0101; OR = 10.222, 95% IC: 1.40–74.55), DQA1*03:02 (p = 0.0051; OR = 5.297, 95% IC: 1.48–19.02), and DRB1*09:01 (p = 0.0119; OR = 4.788, 95% IC: 1.39–16.44) showed an association with susceptibility to HIV infection, while DQB1*03:419 (p = 0.0478; OR = 0.327, 95% IC: 0.11–0.96) was associated with protection from HIV infection. Our findings contribute to the knowledge of HLA allele diversity in the Peruvian population (around 70% South American indigenous ancestry) lays the groundwork for further valuable large-scale use of HLA typing and offers a novel association with HIV infection that is relevant to vaccine studies.