A metagenome-wide association study of HIV disease progression in HIV controllers

Luis Miguel Real; María E Sáez; Anais Corma-Gómez; Antonio Gonzalez-Pérez; Christian Thorball; Rocío Ruiz; María Reyes Jimenez-Leon; Alejandro Gonzalez-Serna; Carmen Gasca-Capote; María José Bravo; José Luis Royo; Alberto Perez-Gomez; María Inés Camacho-Sojo; Isabel Gallego; Joana Vitalle; Sara Bachiller; Alicia Gutierrez-Valencia; Francisco Vidal; Jacques Fellay; Mathias Lichterfeld; Ezequiel Ruiz-Mateos; Swiss HIV Cohort Study

doi:10.1016/j.isci.2023.107214

A metagenome-wide association study of HIV disease progression in HIV controllers

iScience. 2023 Jun 26;26(7):107214. doi: 10.1016/j.isci.2023.107214. eCollection 2023 Jul 21.

Authors

Luis Miguel Real^{1

2

3}, María E Sáez⁴, Anais Corma-Gómez^{1

3}, Antonio Gonzalez-Pérez⁴, Christian Thorball^{5

6}, Rocío Ruiz⁷, María Reyes Jimenez-Leon⁸, Alejandro Gonzalez-Serna^{1

3}, Carmen Gasca-Capote⁸, María José Bravo², José Luis Royo², Alberto Perez-Gomez⁸, María Inés Camacho-Sojo⁸, Isabel Gallego⁸, Joana Vitalle⁸, Sara Bachiller^{8

9}, Alicia Gutierrez-Valencia⁸, Francisco Vidal^{3

10

11

12}, Jacques Fellay^{5

6}, Mathias Lichterfeld^{13

14

15

16}, Ezequiel Ruiz-Mateos⁸; Swiss HIV Cohort Study

Affiliations

¹ Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen de Valme, Instituto de Biomedicina de Sevilla, IBIS, Sevilla, Spain.
² Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.
³ Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)-Instituto de Salud Carlos III, Madrid, Spain.
⁴ Centro Andaluz de Estudios Bioinformáticos (CAEBI, SL), Sevilla, Spain.
⁵ School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
⁶ Precision Medicine Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
⁷ Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla/Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Sevilla, Spain.
⁸ Institute of Biomedicine of Seville, IBiS/Virgen del Rocío University Hospital/CSIC/University of Seville, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Seville, Spain.
⁹ Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain.
¹⁰ Hospital Universitari de Tarragona Joan XXIII (HJ23), Tarragona, Spain.
¹¹ Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
¹² Universitat Rovira i Virgili (URV), Tarragona, Spain.
¹³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
¹⁴ Harvard Medical School, Boston, MA, USA.
¹⁵ Infectious Disease Division, Massachusetts General Hospital, Boston, MA, USA.
¹⁶ Infectious Disease Division, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

Some HIV controllers experience immunologic progression with CD4⁺ T cell decline. We aimed to identify genetic factors associated with CD4⁺ T cell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]), MICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p = 0.017; OR = 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

Keywords: Biological sciences; Health sciences; Immunology; Medicine; Natural sciences.