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1. Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis

Author

Armani-Tourret, Marie, Zhou, Zhicheng, Gasser, Romain, Staropoli, Isabelle, Cantaloube-Ferrieu, Vincent, Benureau, Yann, Garcia-Perez, Javier, Pérez-Olmeda, Mayte, Lorin, Valérie, Puissant-Lubrano, Bénédicte, Assoumou, Lambert, Delaugerre, Constance, Lelièvre, Jean-Daniel, Lévy, Yves, Mouquet, Hugo, Martin-Blondel, Guillaume, Alcami, Jose, Arenzana-Seisdedos, Fernando, Izopet, Jacques, Colin, Philippe, Lagane, Bernard, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogénie Virale, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Salud Carlos III [Madrid] (ISC), Immunologie humorale - Humoral Immunology, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Henri Mondor, Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire de Virologie [Toulouse], This work was supported by Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) (http://www.anrs.fr/fr) (Grants AAP-2013-2 and ECTZ63419 to B.L.), Institut National de la Santé et de la Recherche Médicale (INSERM) (https://www.inserm.fr), Institut Pasteur (https://www.pasteur.fr), Université Paul Sabatier Toulouse III (https://www.univ-tlse3.fr), The Milieu Intérieur Program (ANR-10-LABX-69-01 to H.M.) (http://www.milieuinterieur.fr) and Instituto de Salud Carlos III (projects RD16CIII/0002/0001 and PI19CIIII/0004 to J.A.) (https://www.isciii.es). M.A.-T. was supported by a grant from Sidaction (https://www.sidaction.org/)., ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Agence Nationale de Recherches sur le sida et les hépatites virales (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Institut Pasteur, Paul Sabatier University (Francia), Milieu Intérieur Program, Instituto de Salud Carlos III, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Gestionnaire, Hal Sorbonne Université, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Institut National de la Santé et de la Recherche Médicale (France), and Université Paul Sabatier Toulouse III

Subjects
RNA viruses, CD4-Positive T-Lymphocytes, MESH: CD4-Positive T-Lymphocytes / virology, [SDV]Life Sciences [q-bio], HIV Infections, chemokines, Pathology and Laboratory Medicine, MESH: Viral Envelope Proteins / metabolism, MESH: Virulence Substances, White Blood Cells, Spectrum Analysis Techniques, cell staining, Immunodeficiency Viruses, Viral Envelope Proteins, Animal Cells, Medicine and Health Sciences, Homeostasis, viral tropism, MESH: HIV Infections / physiopathology, Biology (General), Virulence, T Cells, Chemotaxis, MESH: Antiviral Agents / metabolism, Flow Cytometry, MESH: Chemokine CXCL12 / metabolism, [SDV] Life Sciences [q-bio], Cell Motility, Medical Microbiology, Spectrophotometry, MESH: Homeostasis, Viruses, Cytophotometry, Pathogens, Cellular Types, Research Article, Cell Physiology, Receptors, CXCR4, QH301-705.5, Immune Cells, Immunology, cloning, MESH: HIV-1 / physiology, MESH: HIV-1 / pathogenicity, Research and Analysis Methods, Microbiology, Antiviral Agents, MESH: HIV Infections / transmission, MESH: Receptors, CXCR4 / metabolism, Retroviruses, Humans, MESH: HIV Infections / virology, Molecular Biology Techniques, cell binding, Microbial Pathogens, Molecular Biology, Blood Cells, cell fusion, MESH: Humans, Lentivirus, Organisms, Biology and Life Sciences, HIV, Cell Biology, RC581-607, Chemokine CXCL12, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, HIV-1, viral pathogens, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Immunologic diseases. Allergy
Abstract

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART., Author summary HIV-1 infects immune cells by binding CD4 and a coreceptor, CCR5 or CXCR4. CXCR4-using viruses are thought to accelerate depletion of CD4 T lymphocytes (CD4TL) and AIDS development. This paradigm, while often true, is however not seen in all patients, suggesting heterogeneity in the virulence of viruses. Here, we show that CXCR4-using viruses can be discriminated on the basis of their resistance to the anti-HIV-1 effect of the CXCR4 chemokine CXCL12. Resistant (RES) viruses are found in patients with low CD4TL levels. They are featured by unique properties of their envelope glycoprotein and the way they use CXCR4. Our data also indicate that RES viruses could contribute to CD4TL depletion. They more effectively kill bystander activated effector memory CD4TL, a subset of CD4TL enriched in HIV+ patients, and enter CD4TL subsets surrounded by CXCL12. Resistance could therefore enhance the ability of viruses to target naive cells and their precursors in lymphoid organs where CXCL12 is present, further hindering CD4TL renewal. Beyond presenting a novel view of CXCR4-using HIV-1 pathogenesis, this work also opens new therapeutic perspectives and increases our knowledge of the still debated role of CXCL12 in HIV-1 transmission.

Published
2021

2. Th22 cells are efficiently recruited in the gut by CCL28 as an alternative to CCL20 but do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals

Author

Guillaume Martin-Blondel, Jacques Izopet, Mary Requena, Bertrand Suc, Laurent Alric, Manon Nayrac, Nicolas Carrere, Pierre Delobel, Karl Barange, Claire Loiseau, Michelle Cazabat, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), James Cook University (JCU), Chirurgie Générale et Digestive [Rangueil], Université de Toulouse (UT), Pôle Maladies de l'appareil digestif [CHU Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Université Fédérale Toulouse Midi-Pyrénées, Service de Gastro-entérologie - Hépatologie [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, Chemokine, [SDV]Life Sciences [q-bio], HIV Infections, C-C chemokine receptor type 6, MESH: Antiretroviral Therapy, Highly Active, 0302 clinical medicine, T-Lymphocyte Subsets, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, MESH: HIV Infections / metabolism, Immunology and Allergy, CCR10, Intestinal Mucosa, MESH: T-Lymphocyte Subsets / metabolism, biology, MESH: Host-Pathogen Interactions / immunology, hemic and immune systems, MESH: Inflammation Mediators / metabolism, 3. Good health, Cell biology, Chemotaxis, Leukocyte, Chemokines, CC, Host-Pathogen Interactions, MESH: T-Lymphocyte Subsets / immunology, Cytokines, MESH: Chemotaxis, Leukocyte / genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Intestinal Mucosa / metabolism, Antibody, Inflammation Mediators, MESH: Host-Pathogen Interactions / genetics, MESH: Chemokines, CC / metabolism, Immunology, MESH: HIV Infections / drug therapy, MESH: Chemokine CCL20 / metabolism, chemical and pharmacologic phenomena, 03 medical and health sciences, Humans, MESH: HIV Infections / virology, MESH: Intestinal Mucosa / immunology, MESH: Chemotaxis, Leukocyte / immunology, Chemokine CCL20, MESH: Humans, MESH: Cytokines / metabolism, Chemotaxis, CCL20, 030104 developmental biology, MESH: HIV-1 / immunology, biology.protein, HIV-1, MESH: Biomarkers, CCL28, Ex vivo, Biomarkers, 030215 immunology, MESH: HIV Infections / immunology
Abstract

International audience; Gut CD4+ T cells are incompletely restored in most HIV-1-infected individuals on antiretroviral therapy, notably Th17 cells, a key subset in mucosal homeostasis. By contrast, gut Th22 cells are usually restored at normal frequencies. Th22 cells display a CCR6+CCR10+ phenotype and could thus respond to CCL20- and CCL28-mediated chemotaxis, while Th17 cells, which express CCR6 but not CCR10, depend on CCL20. Herein, we found that CCL28 is normally expressed by duodenal enterocytes of treated HIV-1-infected individuals, while CCL20 expression is blunted. Ex vivo, we showed that Th22 cells contribute to the reduction of CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Th22 cells preferentially migrate via CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals, Th22 cells can migrate via the CCR10-CCL28 axis, as an alternative to CCR6-CCL20. This could explain the better reconstitution of gut Th22 compared with Th17 cells on antiretroviral therapy. Lastly, we assessed the relationships between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation, and showed that Th22 cells do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.

Published
2020

3. New HIV-1 circulating recombinant form 94: from phylogenetic detection of a large transmission cluster to prevention in the age of geosocial-networking apps in France, 2013 to 2017

Author

Ali Si-Mohammed, Jean-Dominique Poveda, Theresa Rabenja, B Visseaux, Karl Stefic, Fabienne De Oliveira, Anne Signori-Schmuck, Audrey Mirand, Magali Bouvier-Alias, Stéphanie Raymond, Vincent Calvez, Pantxika Bellecave, Coralie Pallier, Anne-Geneviève Marcelin, Véronique Schneider, Sidonie Lambert-Niclot, Chakib Alloui, Marie-Laure Chaix, Jean-Christophe Plantier, Diane Descamps, Elisabeth André-Garnier, Brice Malve, Marc Wirden, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire CERBA [Saint Ouen l'Aumône], Grand Hôpital de l'Est Francilien (GHEF), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Mzembaba, Sandy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Caen Normandie (UNICAEN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]

Subjects
Male, 0301 basic medicine, Epidemiology, HIV Infections, Disease Outbreaks, Men who have sex with men, MESH: HIV Infections / epidemiology, Sexual and Gender Minorities, 0302 clinical medicine, Pandemic, Cluster Analysis, 030212 general & internal medicine, MESH: Phylogeny, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: HIV cluster, HIV CRF94, phylogenetic analysis, HIV Outbreak, HIV Prevention, Recombination, Genetic, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, education.field_of_study, MESH: France / epidemiology, Surveillance, Virulence, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), Viral Load, MESH: Drug Resistance, Viral / genetics, 3. Good health, MESH: HIV-1 / genetics, Phylogeography, MESH: Online Social Networking, Online Social Networking, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, MESH: Disease Outbreaks / prevention & control, Adult, medicine.medical_specialty, Population, MESH: HIV-1 / classification, MESH: HIV-1 / pathogenicity, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Disease cluster, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, MESH: HIV Infections / transmission, 03 medical and health sciences, Virology, Environmental health, Drug Resistance, Viral, medicine, Humans, MESH: DNA, Viral / genetics, MESH: HIV Infections / virology, Viremia, MESH: HIV Infections / prevention & control, education, Genotyping, Whole Genome Sequencing, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Cluster Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, HIV cluster, 030104 developmental biology, DNA, Viral, HIV-1, Observational study, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Sequence Alignment
Abstract

Background Ending the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages. Aim This observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF’s novelty as well as measures to control its spread are presented. Methods Phylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases’ clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire. Results The transmission cluster comprised 49 cases, mostly diagnosed in 2016–2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log10 copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken. Conclusion We advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.

Published
2019

4. Performance evaluation of the Vela Dx Sentosa next-generation sequencing system for HIV-1 DNA genotypic resistance

Author

Pierre Delobel, Caroline Lefebvre, Stéphanie Raymond, Jacques Izopet, Florence Nicot, Luce Minier, Guillaume Martin-Blondel, Romain Carcenac, Florence Abravanel, Agnès Harter, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Genotyping Techniques, MESH: High-Throughput Nucleotide Sequencing / methods, [SDV]Life Sciences [q-bio], MESH: Automation, Laboratory, Integrase inhibitor, HIV Infections, Integrase, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030212 general & internal medicine, Longitudinal Studies, MESH: Longitudinal Studies, Sanger sequencing, DNA genotyping, MESH: Genotyping Techniques / methods, High-Throughput Nucleotide Sequencing, Viral Load, MESH: Drug Resistance, Viral / genetics, MESH: HIV-1 / genetics, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, symbols, RNA, Viral, MESH: RNA, Viral / blood, MESH: Viral Load, Viral load, HIV drug resistance, MESH: Mutation, 030106 microbiology, Biology, MESH: HIV-1 / drug effects, DNA sequencing, Deep sequencing, 03 medical and health sciences, symbols.namesake, Virology, Drug Resistance, Viral, Reverse transcriptase, MESH: HIV Infections / virology, Humans, Genotyping, Automation, Laboratory, MESH: Humans, DNA extraction, Drug resistance, Mutation, Next-generation sequencing, HIV-1
Abstract

International audience; Background: Patients on antiretroviral therapy could benefit from HIV-1 DNA resistance genotyping for exploring virological failure with low viral load or to guide treatment simplification. Few new generation sequencing data are available.Objective: To check that the automated deep sequencing Sentosa platform (Vela DX) detected minority resistant variants well enough for HIV DNA genotyping.Study design: We evaluated the Sentosa SQ HIV genotyping assay with automated extraction on 40 DNA longitudinal samples from treatment-experienced patients by comparison with Sanger sequencing. HIV drug resistance was interpreted using the ANRS algorithm (v29) at the threshold of 20 % and 3 %.Results: The Sentosa SQ HIV genotyping assay was 100 % successful to amplify and sequence PR and RT and 86 % to amplify and sequence IN when the HIV DNA load was >2.5 log copies/million cells. The Sentosa and Sanger sequencing were concordant for predicting PR-RT resistance at the threshold of 20 % in 14/18 samples successfully sequenced. A higher level of resistance was predicted by Sentosa in three samples and by Sanger in one sample. The prevalence of resistance was 7 % to PI, 59 % to NRTI, 31 % to NNRTI and 20 % to integrase inhibitors using the Sentosa SQ genotyping assay at the threshold of 3 %. Seven additional mutations

Published
2019

5. Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry

Author

Mzoughi, Olfa, Teixido, Meritxell, Planès, Rémi, Serrero, Manutea, Hamimed, Ibtissem, Zurita, Esther, Moreno, Miguel, Granados, Giovana, Lakhdar-Ghazal, Faouzi, BenMohamed, Lbachir, Giralt, Ernest, Bahraoui, Elmostafa, CARBILLET, Véronique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), and University of Barcelona

Subjects
Protein Conformation, alpha-Helical, Protein Conformation, HIV Infections, MESH: Peptide Fragments / pharmacology, MESH: Drug Design, Membrane Fusion, MESH: Membrane Fusion / drug effects, MESH: Circular Dichroism, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, inhibitors, Research Articles, MESH: HIV Envelope Protein gp41 / chemistry, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Circular Dichroism, N36, HIV Envelope Protein gp41, AIDS, trimers, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV/AIDS, Infection, Research Article, Biochemistry & Molecular Biology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / pathogenicity, MESH: HIV-1 / drug effects, Vaccine Related, MESH: HIV Infections / genetics, MESH: HIV Envelope Protein gp41 / pharmacology, Humans, MESH: HIV Infections / virology, Amino Acid Sequence, Vaccine Related (AIDS), C34, MESH: Protein Conformation, alpha-Helical, MESH: Humans, Prevention, alpha-Helical, MESH: Amino Acid Sequence / genetics, Peptide Fragments, Good Health and Well Being, Drug Design, MESH: Peptide Fragments / chemical synthesis, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Immunization, Biochemistry and Cell Biology, MESH: Peptide Fragments / chemistry, MESH: HIV Envelope Protein gp41 / chemical synthesis
Abstract

International audience; The trimeric heptad repeat domains HR1 and HR2 of the human immunodeficiency virus 1 (HIV-1) gp41 play a key role in HIV-1-entry by membrane fusion. To develop efficient inhibitors against this step, the corresponding trimeric-N36 and C34 peptides were designed and synthesized. Analysis by circular dichroism of monomeric and trimeric N36 and C34 peptides showed their capacities to adopt α-helical structures and to establish physical interactions. At the virological level, while trimeric-C34 conserves the same high anti-fusion activity as monomeric-C34, trimerization of N36-peptide induced a significant increase, reaching 500-times higher in anti-fusion activity, against R5-tropic virus-mediated fusion. This result was associated with increased stability of the N36 trimer peptide with respect to the monomeric form, as demonstrated by the comparative kinetics of their antiviral activities during 6-day incubation in a physiological medium. Collectively, our findings demonstrate that while the trimerization of C34 peptide had no beneficial effect on its stability and antiviral activity, the trimerization of N36 peptide strengthened both stability and antiviral activity. This approach, promotes trimers as new promising HIV-1 inhibitors and point to future development aimed toward innovative peptide fusion inhibitors, microbicides or as immunogens.

Published
2019

6. Once‐daily darunavir/ritonavir 400/100 mg in triple therapy: efficacy and penetration in seminal compartment in ANRS ‐165 DARULIGHT study

Author

François Raffi, Jean-Michel Molina, Christine Katlama, Marie-Laure Chaix, Juliette Saillard, Minh Patrick Lê, Gilles Peytavin, Sylvie Chevret, Sebastien Gallien, Yazdan Yazdanpanah, Pierre Delobel, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Services de Maladies Infectieuses et Tropicales [CHU Bichat], ANRS France Recherche Nord & sud Sida-hiv hépatites, Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Pistre, Karine

Subjects
Darunavir+Ritonavir, unbound total, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], MESH: HIV Infections / drug therapy, MESH: Darunavir / pharmacokinetics, darunavir, Pharmacology, MESH: Drug Administration Schedule, MESH: HIV-1 / drug effects, seminal and blood plasma, MESH: HIV Infections / blood, MESH: Dose-Response Relationship, Drug, MESH: HIV-1 / isolation & purification, medicine, MESH: HIV Infections / virology, Pharmacology (medical), Therapy efficacy, Letter to the Editor, Darunavir, MESH: Drug Combinations, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, MESH: Drug Therapy, Combination / methods, MESH: Adult, Penetration (firestop), MESH: Darunavir / administration & dosage, MESH: HIV-1 / genetics, [SDV] Life Sciences [q-bio], MESH: HIV Protease Inhibitors / pharmacokinetics, dose reduction, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Dose reduction, MESH: HIV Protease Inhibitors / administration & dosage, Once daily, business, medicine.drug
Abstract

International audience; A key concern for reduced-dose antiretroviral regimens in maintenance strategies in HIV-infected patients is virological efficacy, as assessed by the suppression of HIV-RNA in blood and reservoirs, such as the genital tract. The risk of minority variants emerging in reservoirs with different antiretroviral drug penetrations and immune pressures is also a matter of concern [1–4]. Thus, antiviral activity and drug penetration into deep compartments must be considered in reduced-dose strategies.

Published
2019

7. Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen

Author

Jacques Izopet, Chloé Dimeglio, Florence Nicot, Caroline Lefebvre, Romain Carcenac, Nicolas Jeanne, Stéphanie Raymond, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Mzembaba, Sandy

Subjects
0301 basic medicine, Oncology, Male, [SDV]Life Sciences [q-bio], hiv, HIV Infections, Drug resistance, viral load result, MESH: Genotype, Virological response, chemistry.chemical_compound, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Genotype, rna-directed dna polymerase, Pharmacology (medical), 030212 general & internal medicine, genes, MESH: High-Throughput Nucleotide Sequencing, ComputingMilieux_MISCELLANEOUS, MESH: Treatment Outcome, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Antiretroviral Therapy, High-Throughput Nucleotide Sequencing, Viral Load, virology, MESH: HIV-1 / genetics, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Treatment Outcome, genotype determination, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Rilpivirine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Drug Resistance, Female, MESH: Rilpivirine / pharmacology, MESH: Viral Load, Viral hepatitis, Viral load, Microbiology (medical), medicine.medical_specialty, MESH: Mutation, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: Highly Active, Genome, Viral, MESH: HIV-1 / drug effects, MESH: Viral, MESH: Rilpivirine / therapeutic use, 03 medical and health sciences, massively-parallel genome sequencing, Internal medicine, Drug Resistance, Viral, medicine, MESH: HIV Infections / virology, Humans, MESH: Genome, Genotyping, plasma, Pharmacology, business.industry, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Regimen, chemistry, Mutation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, HIV-1, business
Abstract

Author(s): Dimeglio, Chloe; Raymond, Stephanie; Nicot, Florence; Jeanne, Nicolas; Carcenac, Romain; Lefebvre, Caroline; Izopet, Jacques; French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group | Abstract: ObjectivesTo determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.Patients and methodsFour hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P l 0.01). The VR at 12 months decreased from 96.9% to 83.4% when the mutational load was g1700 copies/mL and to 50% when the mutational load was g 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8).ConclusionsThere is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of l 20% together with the plasma HIV-1 viral load at the time of resistance genotyping.

Published
2018

8. HIV-1 Tropism and Liver Fibrosis in HIV–HCV Co-Infected Patients

Author

Florence Abravanel, Stéphanie Raymond, Elodie Pambrun, Maria Winnock, Philippe Bonnard, Philippe Sogni, Pascale Trimoulet, François Dabis, Dominique Salmon-Ceron, Jacques Izopet, ANRS CO13 HEPAVIH Study Group, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU de Bordeaux Pellegrin [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Pagès, Nathalie

Subjects
Liver Cirrhosis, Male, viruses, [SDV]Life Sciences [q-bio], MESH: HIV Infections / complications, HIV Infections, Hepacivirus, medicine.disease_cause, MESH: Antiretroviral Therapy, Highly Active, Fibrosis, Antiretroviral Therapy, Highly Active, MESH: Hepatocytes / metabolism, Multidisciplinary, Coinfection, virus diseases, Hepatitis C, Middle Aged, MESH: Hepatocytes / pathology, MESH: RNA, Viral / biosynthesis, [SDV] Life Sciences [q-bio], Disease Progression, RNA, Viral, Infectious diseases, Medicine, Female, HIV clinical manifestations, Research Article, Adult, Receptors, CXCR4, Viral Entry, Receptors, CCR5, Hepatitis C virus, Science, Gastroenterology and Hepatology, Viral diseases, Biology, Antiviral Agents, Microbiology, Virus, MESH: HIV Infections / pathology, MESH: Receptors, CXCR4 / metabolism, Virology, Hepatic Stellate Cells, medicine, HIV tropism, Humans, MESH: HIV Infections / virology, Tropism, Aged, HIV, MESH: Receptors, CCR5 / metabolism, MESH: Adult, medicine.disease, MESH: Liver Cirrhosis / virology, MESH: Hepatocytes / virology, Viral Tropism, MESH: Hepatitis C / virology, Immunology, HIV-1, Hepatocytes, Tissue tropism, MESH: Hepatitis C / pathology, Viral Transmission and Infection, MESH: Liver Cirrhosis / drug therapy
Abstract

Background and aimsHepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients.MethodsWe used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness.ResultsInitially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: ConclusionsThe presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis.

Published
2012

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