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oai:repisalud.isciii.es:20.500.12105/87072025-04-10T08:59:01Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16938col_20.500.12105_16958col_20.500.12105_16961col_20.500.12105_16964

00925njm 22002777a 4500 dc Ramirez de Arellano, Eva author Díez-Fuertes, Francisco author Aguilar, Francisco author de la Torre-Tarazona, Humberto Erick author Sanchez-Lara, Susana author Lao, Yolanda author Vicario, José Luis author García, Felipe author González-García, Juan author Pulido, Federico author Gutierrez-Rodero, Félix author Moreno, Santiago author Iribarren, Jose Antonio author Viciana, Pompeyo author Vilches, Carlos author Ramos, Manuel author Capa, Laura author Alcamí, José author Val, Margarita del author 2019 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. PLoS One. 2019 Aug 8;14(8):e0220459. 10.1371/journal.pone.0220459 1932-6203 1932-6203 PloS one 31393887 http://hdl.handle.net/20.500.12105/8707 Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients