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http://purl.uniprot.org/citations/27986689http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27986689http://www.w3.org/2000/01/rdf-schema#comment"

Background

HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers.

Methods

We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C.

Conclusions

We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.org/dc/terms/identifier"doi:10.1093/cid/ciw833"xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Moreno S."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Vidal F."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Hua S."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Rodriguez C."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Walker B.D."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Ruiz-Mateos E."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Gonzalez-Escribano M.F."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Capa L."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Alcami J."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Del Val M."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Yu X.G."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Del Romero J."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Leal M."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Lichterfeld M."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Dominguez-Molina B."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Ramirez de Arellano E."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Rodriguez-Gallego E."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Tarancon-Diez L."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Viciana P."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Tural C."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Abad-Molina C."xsd:string
http://purl.uniprot.org/citations/27986689http://purl.uniprot.org/core/author"Machmach K."xsd:string
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