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Title: Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
Author: Ramirez de Arellano, Eva
Diez Fuertes, Francisco
Aguilar, Francisco
Torre Tarazona, Humberto Erick de la
Sánchez Lara, Susana
Lao, Yolanda
Vicario, Jose Luis
García, Felipe
González García, Juan
Pulido, Federico
Gutiérrez Rodero, Felix
Moreno, Santiago
Antonio Iribarren, Jose
Viciana, Pompeyo
Vilches, Carlos
Ramos, Manuel
Capa, Laura
Alcamí, José
Val, Margarita del
Keywords: Antígens HLA
VIH (Virus)
Polimorfisme (Cristal·lografia)
HLA histocompatibility antigens
HIV (Viruses)
Polymorphism (Crystallography)
Issue Date: 8-Aug-2019
Publisher: Public Library of Science (PLoS)
Abstract: Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.
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It is part of: PLoS One, 2019, vol. 14, num. 8, p. e0220459
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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