{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:24:07Z","timestamp":1780590247988,"version":"3.54.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background.<\/jats:title>\n                  <jats:p>Human immunodeficiency virus type 1 (HIV-1) controllers maintain HIV-1 viremia at low levels (normally &amp;lt;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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>We analyzed the association of interferon-lambda 4 (IFNL4)\u2013related polymorphisms and human leukocyte antigen (HLA)-B haplotypes within long-term nonprogressor HIV-1 controllers (LTNP-Cs; defined by maintaining CD4+ T-cells counts &amp;gt;500 cells\/mm3 for more than 7 years after HIV-1 diagnosis) vs non-LTNP-Cs who developed CD4+ T-cell counts &amp;lt;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\u2013specific T-cell responses and soluble cytokines were analyzed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>HLA-B*57 was independently associated with the LTNP-C phenotype (odds ratio [OR], 3.056 [1.029\u20139.069]; P = .044 and OR, 1.924 [1.252\u20132.957]; P = .003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT\/TT, ss469415590; OR, 0.401 [0.171\u20130.942]; P = .036 or A\/A, rs12980275; OR, 0.637 [0.434\u20130.934]; 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-\u03b3 (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-\u03b3 +CD57- HIV-1\u2013specific CD8+ T cells (P = .002 and .041, respectively) than non-LTNP-Cs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions.<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciw833","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T12:05:45Z","timestamp":1481198745000},"page":"621-628","source":"Crossref","is-referenced-by-count":27,"title":["HLA-B*57 and IFNL4-Related Polymorphisms Are Associated With Protection Against HIV-1 Disease Progression in Controllers"],"prefix":"10.1093","volume":"64","author":[{"given":"Beatriz","family":"Dominguez-Molina","sequence":"first","affiliation":[{"name":"Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital\/CSIC\/University of Seville, Seville, Spain 1 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tarancon-Diez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital\/CSIC\/University of Seville, Seville, Spain 1 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Hua","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Harvard Medical School 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Massachusetts General Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Brigham and Women\u2019s Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Abad-Molina","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital 3 , Seville , ;","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Rodriguez-Gallego","sequence":"additional","affiliation":[{"name":"Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili 4 , Tarragona , ;","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawthar","family":"Machmach","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of California 5 , Davis ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Vidal","sequence":"additional","affiliation":[{"name":"Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili 4 , Tarragona , ;","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tural","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Lluita Contra la Sida, Fundacio Irsicaixa, Hospital Universitari Germans Trias i Pujol, Badalona 6 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Ram\u00f3n y Cajal, Universidad de Alcal\u00e1 de Henares, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria, Madrid 7 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Go\u00f1i","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Complejo Hospitalario de Navarra 8 , Pamplona ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ram\u00edrez de Arellano","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda Viral, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III 9 , Madrid , ;","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"del Val","sequence":"additional","affiliation":[{"name":"Unidad de Inmunolog\u00eda Viral, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III 9 , Madrid , ;","place":["Spain"]},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa 10 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Francisca","family":"Gonzalez-Escribano","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital 3 , Seville , ;","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Del Romero","sequence":"additional","affiliation":[{"name":"Centro Sanitario Sandoval, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos 11 , and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Centro Sanitario Sandoval, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos 11 , and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Capa","sequence":"additional","affiliation":[{"name":"AIDS Immunopathology Unit, Instituto de Salud Carlos III 12 , Majadahonda, Madrid , ; and","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pompeyo","family":"Viciana","sequence":"additional","affiliation":[{"name":"Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital\/CSIC\/University of Seville, Seville, Spain 1 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Alcam\u00ed","sequence":"additional","affiliation":[{"name":"AIDS Immunopathology Unit, Instituto de Salud Carlos III 12 , Majadahonda, Madrid , ; and","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu G.","family":"Yu","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Harvard Medical School 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Massachusetts General Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Brigham and Women\u2019s Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Harvard Medical School 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Massachusetts General Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Brigham and Women\u2019s Hospital 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Howard Hughes Medical Institute 13 , Chevy Chase, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Leal","sequence":"additional","affiliation":[{"name":"Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Roc\u00edo University Hospital\/CSIC\/University of Seville, Seville, Spain 1 ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Lichterfeld","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Harvard Medical School 2 , Cambridge, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts , , Boston, Massachusetts ;"},{"name":"Infectious Disease Division, Massachusetts General Hospital 2 , Cambridge, Massachusetts , 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