Author, as appears in the article.: Dominguez-Molina B, Tarancon-Diez L, Hua S, Abad-Molina C, Rodriguez-Gallego E, Machmach K, Vidal F, Tural C, Moreno S, Goñi JM, Ramírez de Arellano E, Del Val M, Gonzalez-Escribano MF, Del Romero J, Rodriguez C, Capa L, Viciana P, Alcamí J, Yu XG, Walker BD, Leal M, Lichterfeld M, Ruiz-Mateos E, ECRIS integrated in the Spanish AIDS Research Network
Department: Bioquímica i Biotecnologia Medicina i Cirurgia
URV's Author/s: Rodríguez Gallego, Esther / Vidal Marsal, Francisco
Keywords: Progression ifnl4 hla-b*57 hiv-controllers
Abstract: Background. Human immunodeficiency virus type 1 (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 analyzed the association of interferon-lambda 4 (IFNL4)-related polymorphisms and human leukocyte antigen (HLA)-B haplotypes within long-term nonprogressor HIV-1 controllers (LTNP-Cs; defined by maintaining CD4+ T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) vs non-LTNP-Cs who developed CD4+ T-cell 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 analyzed. Results. HLA-B∗57 was independently associated with the LTNP-C phenotype (odds ratio [OR], 3.056 [1.029-9.069]; P = .044 and OR, 1.924 [1.252-2.957]; P = .003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590; OR, 0.401 [0.171-0.942]; P = .036 or A/A, rs12980275; OR, 0.637 [0.434-0.934]; P = .021) in the Spanish and validation cohorts, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms, and different HLA-B haplotypes. LTNP-Cs showed lower plasma induced protein 10 (P = .019) and higher IFN-γ (P = .02) levels than the HIV-1 controllers with diminished CD4+ T-cell numbers. Moreover, LTNP-Cs exhibited higher quantities of interleukin (IL)2+CD57- and IFN-γ +CD57-HIV-1-specific CD8+ T cells (P = .002 and .041, respectively) than non-LTNP-Cs. Conclusions. We 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.
Thematic Areas: Saúde coletiva Odontología Microbiology (medical) Microbiology Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Infectious diseases Immunology General medicine Farmacia Engenharias ii Engenharias i Enfermagem Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 10584838
Author's mail: esther.rodriguez@urv.cat francesc.vidal@urv.cat
Author identifier: 0000-0002-6692-6186
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://academic.oup.com/cid/article/64/5/621/2698890
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Clinical Infectious Diseases. 64 (5): 621-628
APA: Dominguez-Molina B, Tarancon-Diez L, Hua S, Abad-Molina C, Rodriguez-Gallego E, Machmach K, Vidal F, Tural C, Moreno S, Goñi JM, Ramírez de Arellano E (2017). HLA-B*57 and IFNL4-Related Polymorphisms Are Associated With Protection Against HIV-1 Disease Progression in Controllers. Clinical Infectious Diseases, 64(5), 621-628. DOI: 10.1093/cid/ciw833
Article's DOI: 10.1093/cid/ciw833
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications
Repositori URV