Human leucocyte antigen (HLA)‐DQB103:02 and HLA‐A02:01 have opposite patterns in their effects on susceptibility to HIV infection

• Published in: HIV medicine 2017-09, Vol.18 (8), p.587-594
• Main Authors: Rallón, N, Restrepo, C, Vicario, JL, Romero, J, Rodríguez, C, García‐Samaniego, J, García, M, Cabello, A, Górgolas, M, Benito, JM
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Antigens; Antiretroviral drugs; Confidence intervals; correlates of immune protection; Correlation analysis; Cross-Sectional Studies; Deoxyribonucleic acid; DNA; Drb1 protein; Female; Genetic Predisposition to Disease; Genotypes; Genotyping Techniques; Health risks; Histocompatibility antigen HLA; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV‐exposed seronegative individuals; HLA-A Antigens - genetics; HLA-A Antigens - metabolism; HLA-DQ beta-Chains - genetics; Human immunodeficiency virus; human leucocyte antigen/killer immunoglobulin receptor; Humans; Infections; Male; Middle Aged; Multivariate analysis; Nucleotide sequence; Oligonucleotides; Patients; Polymerase chain reaction; Receptors, KIR - genetics; Sexual behavior; Sexual intercourse; Spain; susceptibility to HIV infection
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/hiv.12494

Objectives The objective of this study was to seek correlates of immune protection in HIV infection. We sought to elucidate the association between the presence of human leucocyte antigen (HLA) alleles, as well as killer immunoglobulin receptor (KIR) genotypes, and the susceptibility to HIV infection in a Spanish cohort of HIV‐exposed seronegative (HESN) individuals. Methods A total of 152 individuals were evaluated: 29 HESN individuals in stable heterosexual relationships with an HIV‐infected partner admitting high‐risk sexual intercourse for at least 12 months prior to inclusion in the study, 61 HIV‐infected patients and 62 healthy controls. HLA class I and II alleles and KIR genotypes were assessed in genomic DNA from all individuals in the study by polymerase chain reaction−sequence‐specific oligonucleotide (PCR‐SSO) using bead array technology. Results HESN individuals showed a higher prevalence of HLA‐A3 (62%) and HLA‐B44 (83%) supertypes compared with HIV‐infected individuals (42% and 66%, respectively). Regarding specific HLA alleles, HESN individuals had a higher prevalence of HLA‐A*33:01, DRB1*04 and DQB1*03:02 alleles (14%, 34% and 31%, respectively) and a lower prevalence of the HLA‐A*02:01 allele (27%) than HIV‐infected patients (3%, 15%, 11% and 52%, respectively; P < 0.05). Interestingly, in a multivariate analysis, only the presence of DQB1*03:02 and the absence of A*02:01 alleles were independently associated with HESN status [odds ratio (OR) 3.4 (95% confidence interval (CI) 1.1–10.5) and 0.4 (95% CI: 0.1–0.9), respectively; P < 0.05]. No KIR genotype was associated with susceptibility to HIV infection. Conclusions Our data showed that the presence of the HLA class II allele DQB1*03:02 was a correlate of immune protection against HIV infection, while the presence of the HLA class I allele A*02:01 was associated with being infected with HIV.