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1. Anti‐spike <scp>IgG</scp> antibody kinetics following the second and third doses of <scp>BNT162b2</scp> vaccine in nursing home residents

Author: Helene Jeulin, Carlos Labat, Kevin Duarte, Simon Toupance, Gregoire Nadin, Denis Craus, Ioannis Georgiopoulos, Isabelle Gantois, François Goehringer, Athanase Benetos, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine, CNRS, LCPME, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de la Recherche Scientifique (CNRS), Maison Médicale, Rosières-aux-Salines, Université de Lorraine, CHRU-Nancy Brabois, Department of Clinical Geriatrics, Université de Lorraine, CHRU-Nancy Brabois, Department of Infectious and Tropical Diseases, and ANR-15-IDEX-0004
Subjects: Aged, 80 and over, Vaccines, SARS-CoV-2, viruses, COVID-19, nursing homes, Antibodies, Viral, vaccination, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Immunoglobulin G, Humans, RNA, Messenger, Geriatrics and Gerontology, BNT162 Vaccine
Abstract: International audience; Background: Duration of post-vaccination protection against COVID-19 in nursing home (NH) residents is a critical issue. The objective of this study was to estimate the duration of the IgG(S) response to the mRNA BNT162b2 vaccine in NH residents with (COV-Yes) or without (COV-No) history of SARS-CoV-2 infection.Methods: A 574 COV-Yes and COV-No NH residents were included in 2 cohorts: Main (n = 115, median age 87 years) or Confirmatory (n = 459, median age 89 years). IgG(S) quantification was carried out at three different time points following the BNT162b2 vaccine: three (1st) and seven (2nd) months after the 2nd dose, and 1 month after the 3rd dose (3rd quantification) in the Main cohort, and twice (2nd and 3rd) in the Confirmatory cohort. The seroneutralization capacity according to COVID-19 history was also measured in a subgroup of patients.Results: Neutralization capacity was strongly correlated with IgG(S) levels (R2 :76%) without any difference between COV-Yes and COV-No groups for the same levels of IgG(S). After the 2nd dose, duration of the assumed robust protection (IgG(S) >264 BAU/ml) was two-fold higher in the COV-Yes vs. COV-No group: 12.60 (10.69-14.44) versus 5.76 (3.91-8.64) months, with this advantage mainly due to the higher IgG(S) titers after the 2nd dose and secondary to a slower decay over time. After the 3rd dose, duration of robust protection was estimated at 11.87 (9.88-14.87) (COV-Yes) and 8.95 (6.85-11.04) (COV-No) months. These results were similar in both cohorts.Conclusions and relevance: In old subjects living in NH, history of SARS-CoV-2 infection provides a clear advantage in the magnitude and duration of high IgG(S) titers following the 2nd dose. Importantly, the 3rd dose induces a much more pronounced IgG(S) response than the 2nd dose in COV-No subjects, the effect of which should be able to ensure a prolonged protection against severe forms of COVID-19 in these subjects.
Published: 2022
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2. Fatal Cowpox Virus Infection in Human Fetus, France, 2017

Author: Sandrine Henard, Isabelle Drouet, Evelyne Schvoerer, Christophe N. Peyrefitte, Olivier Ferraris, Estelle Mosca, Gaelle Frenois-Veyrat, Fanny Jarjaval, Laetitia Boutin, Hawa Timera, Audrey Ferrier, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), and Service de Santé des Armées
Subjects: Microbiology (medical), Epidemiology, viruses, cowpox virus, orthopoxvirus, Infectious and parasitic diseases, RC109-216, fetal mortality, Virus, Young Adult, chemistry.chemical_compound, Fetus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Animals, Humans, Fatal Cowpox Virus Infection in Human Fetus, France, 2017, Smallpox, Orthopoxvirus, Fetal Death, Pregnancy, biology, business.industry, Research, Cowpox virus, Cowpox, virus diseases, biology.organism_classification, medicine.disease, Virology, infection, Vaccination, Infectious Diseases, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Female, France, Variola virus, Vaccinia, business
Abstract: Cowpox virus (CPXV) has an animal reservoir and is typically transmitted to humans by contact with infected animals. In 2017, CPXV infection of a pregnant woman in France led to the death of her fetus. Fetal death after maternal orthopoxvirus (smallpox) vaccination has been reported; however, this patient had not been vaccinated. Investigation of the patient’s domestic animals failed to demonstrate prevalence of CPXV infection among them. The patient’s diagnosis was confirmed by identifying CPXV DNA in all fetal and maternal biopsy samples and infectious CPXV in biopsy but not plasma samples. This case of fetal death highlights the risk for complications of orthopoxvirus infection during pregnancy. Among orthopoxviruses, fetal infection has been reported for variola virus and vaccinia virus; our findings suggest that CPXV poses the same threats for infection complications as vaccinia virus.
Published: 2021
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3. Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19

Author: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati, CHU Henri Mondor [Créteil], Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Ambroise Paré [AP-HP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Bicêtre, Hôpital Paul Brousse, Département des maladies respiratoires [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hopital Saint-Louis [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 de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital Roger Salengro [Lille], Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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], Hôpital Cochin [AP-HP], Service de Virologie [CHU Cochin], Centre Hospitalier Victor Dupouy, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Avicenne [AP-HP], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de Médecine Intensive et Réanimation [Strasbourg], CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier de Saint-Camille [Bry sur Marne], Centre Hospitalier de Melun (CHM), Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IMRB - VHC/'Viruses-Hepatology-Cancers' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Phenotype, Multidisciplinary, SARS-CoV-2, Critical Illness, [SDV]Life Sciences [q-bio], COVID-19, Humans, General Physics and Astronomy, Prospective Studies, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract: Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35–1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.
Published: 2022
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4. Variability in molecular characteristics of Hepatitis E virus quasispecies could modify viral surface properties and transmission

Author: Alexis Gentilhomme, Christophe Gantzer, Evelyne Schvoerer, Honorine Fenaux, Cédric Hartard, Jean-Pierre Bronowicki, M. Bensenane, Elodie Laugel, Thomas Remen, Sibel Berger, Hélène Jeulin, Alexis de Rougemont, Isabelle Bertrand, Elma H. Akand, Armand Maul, John M. Murray, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), School of Mathematics and Statistics, University of New South Wales [Sydney] (UNSW), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Délégation à la Recherche Clinique et à l'Innovation [CHRU Nancy] (DRCI), Service d'Hépato-gastro-entérologie [CHRU Nancy], and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Antigenicity, Surface Properties, Swine, [SDV]Life Sciences [q-bio], viruses, Viral quasispecies, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Hepatitis E virus, Virology, Genotype, medicine, Animals, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, Hepatology, Transmission (medicine), Developed Countries, Pathogenicity, Hepatitis E, 3. Good health, Amino acid, Quasispecies, Infectious Diseases, chemistry, Infected patient, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Rabbits
Abstract: Hepatitis E virus (HEV) usually causes self-limited liver diseases but can also result in severe cases. Genotypes 1 (G1) and 2 circulate in developing countries are human-restricted and waterborne, while zoonotic G3 and G4 circulating in industrialized countries preferentially infect human through consumption of contaminated meat. Our aims were to identify amino acid patterns in HEV variants that could be involved in pathogenicity or in transmission modes, related to their impact on antigenicity and viral surface hydrophobicity. HEV sequences from human (n = 37) and environmental origins (wild boar [n = 3], pig slaughterhouse effluent [n = 6] and urban wastewater [n = 2]) were collected for the characterization of quasispecies using ultra-deep sequencing (ORF2/ORF3 overlap). Predictive and functional assays were carried out to investigate viral particle antigenicity and hydrophobicity. Most quasispecies showed a major variant while a mixture was observed in urban wastewater and in one chronically infected patient. Amino acid signatures were identified, as a rabbit-linked HEV pattern in two infected patients, or the S68L (ORF2) / H81C (ORF3) residue mostly identified in wild boars. By comparison with environmental strains, molecular patterns less likely represented in humans were identified. Patterns impacting viral hydrophobicity and/or antigenicity were also observed, and the higher hydrophobicity of HEV naked particles compared with the enveloped forms was demonstrated. HEV variants isolated from human and environment present molecular patterns that could impact their surface properties as well as their transmission. These molecular patterns may concern only one minor variant of a quasispecies and could emerge under selective pressure.
Published: 2021
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5. Transmission of hepatitis E virus by water: An issue still pending in industrialized countries

Author: Sébastien Berger, Evelyne Schvoerer, H. Fenaux, Isabelle Bertrand, Manon Chassaing, Christophe Gantzer, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Environmental Engineering, viruses, 0208 environmental biotechnology, 02 engineering and technology, Viral quasispecies, 010501 environmental sciences, Biology, medicine.disease_cause, 01 natural sciences, Virus, Hepatitis E virus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, medicine, Animals, Humans, Genetic variability, Waste Management and Disposal, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Water Science and Technology, Civil and Structural Engineering, Infectivity, Transmission (medicine), Developed Countries, Ecological Modeling, Water, virus diseases, Pollution, Virology, digestive system diseases, 6. Clean water, Hepatitis E, 020801 environmental engineering, 3. Good health, Virus Cultivation, Europe, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract: Hepatitis E virus (HEV) is an enteric virus divided into eight genotypes. Genotype 1 (G1) and G2 are specific to humans; G3, G4 and G7 are zoonotic genotypes infecting humans and animals. Transmission to humans through water has been demonstrated for G1 and G2, mainly in developing countries, but is only suspected for the zoonotic genotypes. Thus, the water-related HEV hazard may be due to human and animal faeces. The high HEV genetic variability allows considering the presence in wastewater of not only different genotypes, but also quasispecies adding even greater diversity. Moreover, recent studies have demonstrated that HEV particles may be either quasi-enveloped or non-enveloped, potentially implying differential viral behaviours in the environment. The presence of HEV has been demonstrated at the different stages of the water cycle all over the world, especially for HEV G3 in Europe and the USA. Concerning HEV survival in water, the virus does not have higher resistance to inactivating factors (heat, UV, chlorine, physical removal), compared to viral indicators (MS2 phage) or other highly resistant enteric viruses (Hepatitis A virus). But the studies did not take into account genetic (genogroups, quasispecies) or structural (quasi- or non-enveloped forms) HEV variability. Viral variability could indeed modify HEV persistence in water by influencing its interaction with the environment, its infectivity and its pathogenicity, and subsequently its transmission by water. The cell culture methods used to study HEV survival still have drawbacks (challenging virus cultivation, time consuming, lack of sensitivity). As explained in the present review, the issue of HEV transmission to humans through water is similar to that of other enteric viruses because of their similar or lower survival. HEV transmission to animals through water and how the virus variability affects its survival and transmission remain to be investigated.
Published: 2019
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6. Seroprevalence of SARS-CoV-2, symptom profiles and seroneutralization during the first COVID-19 wave in a suburban area, France

Author: Guillemin F, Legrand K, Hélène Jeulin, Gégout-Petit A, Pierre Vallois, Agathe Bochnakian, Evelyne Schvoerer, Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Gégout-Petit, Anne, and This work was supported by a grant from the Métropole du Grand Nancy, Nancy, France
Subjects: medicine.medical_specialty, Population, Logistic regression, Asymptomatic, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, medicine, Seroprevalence, 030212 general & internal medicine, Young adult, education, Fisher's exact test, 030304 developmental biology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Odds ratio, Confidence interval, 3. Good health, [STAT] Statistics [stat], [STAT]Statistics [stat], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, symbols, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business
Abstract: BackgroundThe World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate anti–SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and describe symptom profiles and in vitro seroneutralization in Nancy, France, in spring 2020.MethodsIndividuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti–SARS-CoV-2 (IgT, i.e. IgA/IgG/IgM) antibodies by ELISA (Bio-rad). Serum samples were classified according to seroneutralization activity >50% (NT50) on Vero CCL-81 cells. Age- and sex-adjusted seroprevalence was estimated. Subgroups were compared by chi-square or Fisher exact test and logistic regression.ResultsAmong 2006 individuals, 43 were SARS-CoV-2–positive; the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), with adjusted metropolitan and national standardized seroprevalence 2.5% (1.8 to 3.3) and 2.3% (1.7 to 3.1). Seroprevalence was highest for 20-to 34-year-old participants (4.7% [2.3 to 8.4]), within than out of socially deprived area (2.5% vs 1%, P=0.02) and with than without intra-family infection (p−6). Moreover, 25% (23 to 27) of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p−13), with anosmia or ageusia highly discriminant (odds ratio 27.8 [13.9 to 54.5]), associated with dyspnea and fever. Among the SARS-CoV-2-positives, 16.3% (6.8 to 30.7) were asymptomatic. For 31 of these individuals, positive seroneutralization was demonstrated in vitro.ConclusionsIn this population of very low anti-SARS-CoV-2 antibody seroprevalence, a beneficial effect of the lockdown can be assumed, with frequent SARS-CoV-2 seroneutralization among IgT-positive patients.Key MessagesTotal immunoglobulin antibody (IgT) measurement is an accurate tool to monitor the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a key biological feature to assume the spread of COVID-19 later after the appearance of symptoms.IgT seroprevalence was 2.1% in the Grand Nancy Metropolitan area, France; was highest for young adults; in socially deprived area, but this was not confirmed at the individual level; and was associated with high intra-family viral transmission.About two thirds of IgT-positive individuals exhibited SARS-CoV-2–positive seroneutralization.Trial registrationNCT04448769
Published: 2021

7. Seroprevalence of SARS-CoV-2, Symptom Profiles and Sero-Neutralization in a Suburban Area, France

Author: Francis Guillemin, Karine Legrand, Nicolas Jay, Agathe Bochnakian, Pierre Vallois, Hélène Jeulin, Evelyne Schvoerer, Anne Gégout Petit, Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Evaluation et Information Médicales [CHRU Nancy], Data Science, Knowledge, Reasoning and Engineering (K Team), Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria), K team (Data Science, Knowledge, Reasoning and Engineering), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), This research was funded by METROPOLE DU GRAND NANCY., and Gégout-Petit, Anne
Subjects: 0301 basic medicine, Male, Cross-sectional study, viruses, [SDV]Life Sciences [q-bio], Antibodies, Viral, 0302 clinical medicine, precariousness, Seroepidemiologic Studies, 030212 general & internal medicine, Young adult, skin and connective tissue diseases, Child, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Aged, 80 and over, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, seroprevalence, virus diseases, Middle Aged, QR1-502, 3. Good health, [SDV] Life Sciences [q-bio], [STAT]Statistics [stat], Infectious Diseases, Child, Preschool, Female, France, Antibody, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Population, Asymptomatic, Microbiology, Article, COVID-19 Serological Testing, symptoms profile, 03 medical and health sciences, Young Adult, Neutralization Tests, Virology, Internal medicine, medicine, Seroprevalence, Humans, education, Aged, business.industry, SARS-CoV-2, fungi, COVID-19, Odds ratio, Confidence interval, [STAT] Statistics [stat], Suburban Population, body regions, 030104 developmental biology, Cross-Sectional Studies, Immunoglobulin M, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunoglobulin G, Communicable Disease Control, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: The World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated anti–SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and in vitro sero-neutralization in Nancy, France, in spring 2020. Individuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti–SARS-CoV-2 (IgT, i.e., IgA/IgG/IgM) antibodies by ELISA (Bio-rad), the sero-neutralization activity was evaluated on Vero CCL-81 cells. Among 2006 individuals, the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), was highest for 20- to 34-year-old participants (4.7% (2.3 to 8.4)), within than out of socially deprived area (2.5% vs 1%, p = 0.02) and with than without intra-family infection (p &lt, 10−6). Moreover, 25% of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p &lt, 10−13), with highly discriminant anosmia or ageusia (odds ratio 27.8 [13.9 to 54.5]), 16.3% (6.8 to 30.7) of seropositive individuals were asymptomatic. Positive sero-neutralization was demonstrated in vitro for 31/43 seropositive subjects. Regarding the very low seroprevalence, a preventive effect of the lockdown in March 2020 can be assumed for the summer, but a second COVID-19 wave, as expected, could be subsequently observed in this poorly immunized population.
Published: 2021
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8. Epidemiological surveillance of SARS-CoV-2 by genome quantification in wastewater applied to a city in the northeast of France: comparison of ultrafiltration- and protein precipitation-based methods

Author: Bertrand, Isabelle, Challant, Julie, Jeulin, Hélène, Hartard, Cédric, Mathieu, Laurence, Lopez, Séverine, Scientific Interest Group Obépine, Schvoerer, Evelyne, Courtois, Sophie, Gantzer, Christophe, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Centre International de Recherche Sur l'Eau et l'Environnement [Suez] (CIRSEE), and SUEZ ENVIRONNEMENT (FRANCE)
Subjects: Veterinary medicine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Ultrafiltration, Genome, Viral, 010501 environmental sciences, Biology, Wastewater, 01 natural sciences, Genome, Article, Disease Outbreaks, Hospitals, University, 03 medical and health sciences, Viral Proteins, Concentration methods, 0302 clinical medicine, Prevalence, Protein precipitation, Chemical Precipitation, Humans, 030212 general & internal medicine, Cities, education, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, education.field_of_study, SARS-CoV-2, Public Health, Environmental and Occupational Health, Outbreak, COVID-19, 6. Clean water, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological surveillance, France, Water Microbiology, Environmental Monitoring
Abstract: The aim of the present study was to develop a simple, sensitive, and specific approach to quantifying the SARS-CoV-2 genome in wastewater and to evaluate this approach as a means of epidemiological surveillance. Twelve wastewater samples were collected from a metropolitan area in north-eastern France during April and May 2020. In addition to the quantification of the SARS-CoV-2 genome, F-specific RNA phages of genogroup II (FRNAPH GGII), naturally present in wastewater, were used as an internal process control for the viral concentration and processing of RT-PCR inhibitors. A concentration method was required to allow the quantification of the SARS-CoV-2 genome over the longest possible period. A procedure combining ultrafiltration, phenol-chloroform-isoamyl alcohol purification, and the additional purification of the RNA extracts was chosen for the quantification of the SARS-CoV-2 genome in 100-mL wastewater samples. At the same time, the COVID-19 outbreak was evaluated through patients from the neighbouring University Hospital of Nancy, France. A regular decrease in the concentration of the SARS-CoV-2 genome from ~104 gc/L to ~102 gc/L of wastewater was observed over the eight weeks of the study, during which the population was placed under lockdown. The SARS-CoV-2 genome was even undetectable during one week in the second half of May and present but non-quantifiable in the last sample (28 May). A concordant circulation in the human community was highlighted by virological diagnosis using respiratory samples, which showed a decrease in the number of COVID-19 cases from 677 to 52 per week over the same period. The environmental surveillance of COVID-19 using a reliable viral quantification procedure to test wastewater is a key approach. The real-time detection of viral genomes can allow us to predict and monitor the circulation of SARS-CoV-2 in clinical settings and survey the entire urban human population.
Published: 2021
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9. Signs of tracheobronchitis may constitute the principal finding on the lung SPECT/CT images of COVID-19 patients

Author: Antoine Verger, Damien Mandry, Hélène Jeulin, Pierre-Yves Marie, Gilles Karcher, Achraf Bahloul, Laetitia Imbert, François Goehringer, BIRKER, Juliette, Nancyclotep- Experimental Imaging Platform = Plate-forme d'imagerie moléculaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Service de Médecine Nucléaire [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de Radiologie adultes [CHRU Nancy], Service de Virologie [CHRU Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: medicine.medical_specialty, Short Communication, Population, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Single-photon emission computed tomography, Scintigraphy, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, CZT-SPECT, 0302 clinical medicine, Tracheobronchitis, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Medicine, Radiology, Nuclear Medicine and imaging, education, Lung, ComputingMilieux_MISCELLANEOUS, Tomography, Emission-Computed, Single-Photon, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, SARS-CoV-2, business.industry, COVID-19, General Medicine, medicine.disease, 3. Good health, Pulmonary embolism, Dyspnea, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, Lung scintigraphy, 030220 oncology & carcinogenesis, Breathing, Bronchitis, Radiology, Tomography, X-Ray Computed, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CT
Abstract: Background This study aimed to analyze the rates of tracheobronchitis signs observed on the ventilation scans of COVID-19 patients with shortness of breath, with comparisons to a non-COVID population. Methods Lung scintigraphy was collected in 10 such COVID patients, as well as from a non-COVID population investigated outside the epidemic wave period, on a CZT-SPECT/CT system, with ventilation images recorded with 99mTc-labeled Technegas® and perfusion images with 99mTc-labeled albumin macroaggregates. Results A diffuse tracheobronchial uptake was observed on the ventilation scans from 3 COVID patients (30%), whereas this rate was 3% (3/90) in the non-COVID group (P = 0.013). These 3 patients had no laryngeal extension of Technegas® uptake and limited parenchymal lung abnormalities. Follow-up scintigraphy demonstrated the withdrawal of tracheobronchitis signs in two cases, and the advent of a severe pulmonary embolism in one. Conclusion Signs of tracheobronchitis may constitute the principal finding on lung SPECT/CT images of COVID-19 patients with shortness of breath.
Published: 2021
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10. CT abnormalities evocative of lung infection are associated with lower 18F-FDG uptake in confirmed COVID-19 patients

Author: Gilles Karcher, Antoine Verger, Hélène Jeulin, Damien Mandry, Laetitia Imbert, Caroline Boursier, Pierre-Yves Marie, Achraf Bahloul, BIRKER, Juliette, Nancyclotep- Experimental Imaging Platform = Plate-forme d'imagerie moléculaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de Radiologie adultes [CHRU Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Male, Lung infection, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Gastroenterology, 030218 nuclear medicine & medical imaging, Serology, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Lung, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Serological tests, General Medicine, Middle Aged, 3. Good health, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, COVID-19 Nucleic Acid Testing, 030220 oncology & carcinogenesis, Female, CT, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Short Communication, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, COVID-19 Serological Testing, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 18F-FDG-PET, Diagnosis, Differential, 03 medical and health sciences, Fluorodeoxyglucose F18, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Aged, business.industry, Bacterial pneumonia, COVID-19, Outbreak, medicine.disease, Orthopedic surgery, Radiopharmaceuticals, Differential diagnosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose CT signs that are evocative of lung COVID-19 infections have been extensively described, whereas 18F-FDG-PET signs have not. Our current study aimed to identify specific COVID-19 18F-FDG-PET signs in patients that were (i) suspected to have a lung infection based on 18F-FDG-PET/CT recorded during the COVID-19 outbreak and (ii) whose COVID-19 diagnosis was definitely established or excluded by appropriate viral testing. Methods Twenty-two consecutive patients referred for routine 18F-FDG-PET/CT examinations during the COVID-19 outbreak (March 25th to May 15th 2020) and for whom CT slices were evocative of a lung infection were included in the study. All patients had undergone a SARS-COV-2 diagnostic test to confirm COVID-19 infection (positivity was based on molecular and/or serological tests) or exclude it (negativity of at least the serological test). Results Eleven patients were confirmed to be affected by COVID-19 (COVID+), whereas the other eleven patients were not (COVID−) and were predominantly suspected of having bacterial pneumonia. CT abnormalities were not significantly different between COVID+ and COVID− groups, although trends toward larger CT abnormalities (p = 0.16) and lower rates of consolidation patterns (0.09) were observed in the COVID+ group. The maximal standardized uptake values (SUVmax) of lung areas with CT abnormalities were however significantly lower in the COVID+ than the COVID− group (3.7 ± 1.9 vs. 6.9 ± 4.1, p = 0.03), with the highest SUVmax consistently not associated with COVID-19. Conclusion Among CT abnormalities evocative of lung infection, those related to COVID-19 are associated with a more limited 18F-FDG uptake. This observation may help improve our ability to detect COVID-19 patients. Electronic supplementary material The online version of this article (10.1007/s00259-020-04999-1) contains supplementary material, which is available to authorized users.
Published: 2021
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11. Co-detection of SARS-CoV-2 and other respiratory pathogens: Lessons from the field to face the second wave

Author: Antoine Goury, Evelyne Schvoerer, Corentine Alauzet, Thomas Guillard, Anaëlle Muggeo, Cédric Hartard, Laurent Andreoletti, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de microbiologie [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: Adult, Male, 2019-20 coronavirus outbreak, Adolescent, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Co detection, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, Humans, Medicine, 030212 general & internal medicine, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, 0303 health sciences, SARS-CoV-2, 030306 microbiology, business.industry, COVID-19, Middle Aged, Respiratory pathogens, Infectious Diseases, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, business
Abstract: International audience
Published: 2020
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12. Full‐length genome sequencing of RNA viruses—How the approach can enlighten us on hepatitis C and hepatitis E viruses

Author: Hélène Jeulin, Sibel Berger, Véronique Venard, Jean-Pierre Bronowicki, Elodie Laugel, Evelyne Schvoerer, Cédric Hartard, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Service d'Hépatogastroentérologie [CHRU Nancy]
Subjects: viruses, Hepatitis C virus, Genomics, Genome, Viral, Hepacivirus, Biology, medicine.disease_cause, Genome, 03 medical and health sciences, 0302 clinical medicine, Hepatitis E virus, Virology, medicine, Animals, Humans, RNA Viruses, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Full length genome, 0303 health sciences, Whole Genome Sequencing, fungi, virus diseases, food and beverages, RNA, Hepatitis C, Hepatitis E, medicine.disease, digestive system diseases, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral
Abstract: Among the five main viruses responsible for human hepatitis, hepatitis C virus (HCV) and hepatitis E virus (HEV) are different while sharing similarities. Both viruses can be transmitted by blood or derivatives whereas HEV can also follow environmental or zoonotic routes. These highly variable RNA viruses can cause chronic hepatitis potentially leading to hepatocarcinoma. HCV and HEV can develop new structures and functions under selective pressure to adapt to host immunity, human tissues, treatments or even various animal reservoirs. Elsewhere, with directly acting antiviral treatments, HCV can be eradicated whereas HEV is an emerging pathogen against which specific treatments have to be improved. As a unique molecular tool able to explore viral genomic plasticity, full-length genome (FLG) sequencing has become easier, faster and cheaper. The present review will show how FLG sequencing can explore these RNA viruses with the aim to investigate key genomics data to improve basic knowledge, patients' healthcare and preventive tools.
Published: 2020
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13. The spectrum of biochemical alterations associated with organ dysfunction and inflammatory status and their association with disease outcomes in severe COVID-19: A longitudinal cohort and time-series design study

Author: Beatrice Maatem Caillierez, Elodie Laugel, Isabelle Aimone-Gastin, Sophie Orlowski, Nathalie Thilly, Bruno Levy, F Barbé, Evelyne Schvoerer, Sébastien Gibot, Luc Frimat, Sybille Bevilacqua, Abderrahim Oussalah, Marie Reine Losser, Antoine Kimmoun, Stanislas Gleye, Jean-Louis Guéant, Marc Merten, Rosa Maria Rodriguez-Gueant, Farès Namour, Isabelle Clerc Urmes, Raphaël Kormann, Elise Jeannesson, Jean Luc Olivier, Catherine Malaplate, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Unité de Méthodologie, Data Managment et Statistiques, Département Méthodologie, Promotion, Investigation (DMPI), Délégation à la Recherche Clinique et à l'Innovation (DRCI), [CHRU Nancy], Service de Virologie [CHRU Nancy], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie [CHRU Nancy], Composés Alimentaires : Biofonctionnalités et risques Neurotoxiques (CALBINOTOX), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service d'Anesthésiologie et de Soins Intensifs [CHRU Nancy], Service de Soins Intensifs [CHRU Nancy], Délégation à la Recherche Clinique et à l'Innovation [CHRU Nancy] (DRCI), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 01 natural sciences, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, 030212 general & internal medicine, 0101 mathematics, Stage (cooking), ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, lcsh:R5-920, Kidney, Lung, business.industry, 010102 general mathematics, Organ dysfunction, Acute kidney injury, General Medicine, Odds ratio, medicine.disease, 3. Good health, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.symptom, lcsh:Medicine (General), Pancreas, business
Abstract: International audience; Background: In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes.Methods: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we used an extensive biochemical dataset of serial data and time-series design to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death.Findings: On the 162 studied patients, 1151 biochemical explorations were carried out for up to 59 biochemical markers, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver, muscle, and pancreas, along with a severe inflammatory syndrome. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36-20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15-13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death.Interpretation: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death.
Published: 2020
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14. Case Series of COVID-19 Asymptomatic Newborns With Possible Intrapartum Transmission of SARS-CoV-2

Author: Jean-Michel Hascoët, Jean-Marc Jellimann, Cedric Hartard, Apolline Wittwer, Hélène Jeulin, Patricia Franck, Olivier Morel, Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Maternité Régionale Adolphe Pinard [Nancy], Service de Médecine Néonatale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Laboratoire de Biologie de la Reproduction et du Développement [CHRU Nancy], Service de Foetopathologie et placentologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Obstétrique et de Gynécologie [CHRU Nancy], Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité. (DevAH), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Asymptomatic, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, newborn, 030225 pediatrics, Pandemic, medicine, antibodies, case report, Pregnancy, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, Obstetrics, Transmission (medicine), business.industry, lcsh:RJ1-570, COVID-19, lcsh:Pediatrics, medicine.disease, 3. Good health, Pediatrics, Perinatology and Child Health, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, vertical transmission, pregnancy, Antibody, medicine.symptom, business, Antibody detection
Abstract: International audience; Background: Despite the pandemic, data are limited regarding COVID-19 infection in pregnant women and newborns. This report aimed to bring new information about presentation that could modify precautionary measures for infants born of mothers with a remote history of COVID-19. Methods: We report two infants with possible maternofetal transmission, and four mothers without immunologic reactions. Data were collected from the patient files.Results: One mother exhibited infection signs 10 days before uncomplicated delivery, with negative RT-PCR and no antibody detection thereafter. Another mother exhibited infection 6 weeks pre-delivery, confirmed by nasopharyngeal swab testing with positive RT-PCR, and positive antibody detection (IgM and IgG). Both newborns were asymptomatic but tested positive for nasopharyngeal and stool RT-PCR at 1 and 3 days of age for the first one and at 1 day of age for stool analysis for the second one. Two additional mothers exhibited infection confirmed by positive RT-PCR testing at 28-and 31-days pre-delivery but did not present detectable antibody reaction at the time of delivery.Conclusion: These observations raise concerns regarding contamination risk by asymptomatic newborns and the efficacy of immunologic reactions in pregnant mothers, questioning the reliability of antibody testing during pregnancy.
Published: 2020
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15. Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France

Author: Elodie Laugel, Isabelle Aimone-Gastin, Isabelle Clerc Urmes, Antoine Kimmoun, Jean-Louis Guéant, Abderrahim Oussalah, Rosa-Maria Rodriguez-Guéant, F Barbé, Sophie Orlowski, Marc Merten, Nathalie Thilly, Sébastien Gibot, Stanislas Gleye, Catherine Malaplate, Beatrice Maatem Caillierez, Jean-Luc Olivier, Raphaël Kormann, Luc Frimat, Farès Namour, Sybille Bevilacqua, Jonas Callet, Bruno Levy, Evelyne Schvoerer, Elise Jeannesson, Marie-Reine Losser, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie [CHRU Nancy], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme [CHRU Nancy], Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Composés Alimentaires : Biofonctionnalités et risques Neurotoxiques (CALBINOTOX), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Réanimation Médicale [CHRU Nancy], Plateforme d'Aide à la Recherche Clinique [CHRU Nancy] (PARC), and Service de Néphrologie [CHRU Nancy]
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, severe COVID-19, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Major Article, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cardiovascular diseases, angiotensin receptor blocker, Creatinine, Kidney, business.industry, SARS-CoV-2, Acute kidney injury, Repeated measures design, Odds ratio, medicine.disease, Confidence interval, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, AcademicSubjects/MED00290, chemistry, angiotensin-converting enzyme inhibitor, acute kidney injury, Cohort, ACE inhibitor, business, medicine.drug
Abstract: Background In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. Methods We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures. Results On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus >40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83–6.14), creatinine >10.1 mg/L (OR, 3.22, 2.28–4.54), and urea nitrogen (UN) >0.52 g/L (OR, 2.65, 95% CI, 1.89–3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17–4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN >0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05–11.96). Conclusions Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure., The present retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19 provides new evidence on the potentially harmful effect of chronic ACEI/ARB use on kidney outcomes and their possible interaction with the occurrence of acute respiratory failure.
Published: 2020
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16. Maraviroc, a future treatment of sarcoidosis? An unexpected drug effect

Author: Goehringer, F, Tiotiu, A, SCHVOERER, Evelyne, Jaussaud, R, Hoen, B, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Service de Virologie [CHRU Nancy]
Subjects: [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020
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17. Coronavirus disease 2019: acute Fanconi syndrome precedes acute kidney injury

Author: Matthieu Garcia Parrilla, Matthieu Koszutski, Paul Voirin, Jean-Louis Guéant, Luc Frimat, Sybille Bevilacqua, Alice Corbel, Asma Alla, Audrey Jacquot, Abderrahim Oussalah, Raphaël Kormann, Bruno Levy, Evelyne Schvoerer, Farès Namour, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Soins Intensifs [CHRU Nancy], Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme [CHRU Nancy], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, and Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Glycosuria, medicine.medical_specialty, 030232 urology & nephrology, Renal function, Gastroenterology, acute proximal tubule injury, hypophosphataemia, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interquartile range, Internal medicine, Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Kidney, Transplantation, Proteinuria, business.industry, SARS-CoV-2, Acute kidney injury, Fanconi syndrome, COVID-19, medicine.disease, 3. Good health, medicine.anatomical_structure, acute kidney injury, Nephrology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Original Article, medicine.symptom, business, Kidney disease
Abstract: Background Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) . Our objective was to determine whether Fanconi syndrome is a frequent clinical feature in coronavirus disease 2019 (COVID-19) patients. Methods A retrospective cohort of 42 laboratory-confirmed COVID-19 patients without history of kidney disease hospitalized in University Hospital of Nancy was investigated. Patients were admitted to the intensive care unit (ICU) (n = 28) or the Medical department (n = 14) and were screened at least once for four markers of proximal tubulopathy. Results The mean (standard deviation) follow-up was 19.7 (±12.2) days. Of the patients, 75% (30/40) showed at least two proximal tubule abnormalities (incomplete Fanconi syndrome). The main disorders were proteinuria (88%, n = 35), renal phosphate leak defined by renal phosphate threshold/glomerular filtration rate (TmPi/GFR) Conclusion Incomplete Fanconi syndrome is highly frequent in COVID-19 patients and precedes AKI or disappears during the recovery phase.
Published: 2020
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18. Apoptosis and autophagy as a turning point in viral–host interactions: the case of human norovirus and its surrogates

Author: Brice Malve, Mihayl Varbanov, Mélanie M Leroux, Alexis Simons, Marc Devocelle, Sean P. Kennedy, Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], CHU Amiens-Picardie, Laboratoire Matériaux et Durabilité des constructions (LMDC), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Royal College of Surgeons in Ireland (RCSI), Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Jean Lamour (IJL), and Université Paris-Saclay, Faculté de Pharmacie, 92290 Châtenay-Malabry, France
Subjects: 0301 basic medicine, Host (biology), viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, Autophagy, Biology, medicine.disease_cause, Virology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Apoptosis, Norovirus, medicine, Turning point
Abstract: International audience; Human gastroenteritis viruses are amid the major causes of disease worldwide, responsible for more than 2 million deaths per year. Human noroviruses play a leading role in the gastroenteritis outbreaks and the continuous emergence of new strains contributes to the significant morbidity and mortality. Many aspects of the viral entry and infection process remain unclear, including the major response of the host cell to the virus, which is the trigger of several programmed cell death related mechanisms. In this review, we assessed apoptosis and autophagy at various stages in the infection process to provide better understanding of the viral–host interaction. This brings us closer to fully understanding how noroviruses work, thus allowing the development of specific antiviral therapies.
Published: 2020
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19. Somatic coliphages are conservative indicators of SARS-CoV-2 inactivation during heat and alkaline pH treatments

Author: Cédric Hartard, Hélène Jeulin, Raphaël E. Duval, J.-F. Loret, Isabelle Bertrand, Stéphanie Philippot, C. Retourney, Mihayl Varbanov, Christophe Gantzer, M. Gardette, Evelyne Schvoerer, Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre International de Recherche Sur l'Eau et l'Environnement [Suez] (CIRSEE), and SUEZ ENVIRONNEMENT (FRANCE)
Subjects: 2019-20 coronavirus outbreak, Veterinary medicine, Environmental Engineering, Hot Temperature, Coronavirus disease 2019 (COVID-19), Somatic cell, PH, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, 010501 environmental sciences, 01 natural sciences, Coliphages, Virus, Article, 03 medical and health sciences, Environmental Chemistry, Humans, Somatic coliphages, skin and connective tissue diseases, Waste Management and Disposal, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Chemistry, SARS-CoV-2, pH, fungi, virus diseases, COVID-19, Hydrogen-Ion Concentration, Pollution, Heat, 6. Clean water, 3. Good health, body regions, Wastewater, Infectivity, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Sludge
Abstract: High concentrations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described in wastewater and sewage sludge. It raises the question of the security of land sludge disposal practices during a pandemic. This study aimed to compare SARS-CoV-2's resistance to the main inactivating factors in sludge treatments, pH and heat, to that of native wastewater somatic coliphages. The latest can be easily used as an indicator of treatment efficiency in the field. The effects of heat treatment and pH on the survival of SARS-CoV-2 and somatic coliphages were investigated in simple media. The T90 value (time required for a 90% reduction in the virus or a 1 × log10 decline) at 50 °C was about 4 min for infectious SARS-CoV-2, and around 133 min for infectious somatic coliphages, with no decrease in SARS-CoV-2 genome. For infectious SARS-CoV-2, a slight decrease (4 log10) can be considered efficient treatments for infectious SARS-CoV-2. We concluded that somatic coliphages can be considered highly conservative and easy to use indicators of the inactivation of SARS-CoV-2 during treatments based on heat and alkaline pH., Graphical abstract Unlabelled Image
Published: 2021
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20. 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
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21. Emerging hepatitis E virus compared with hepatitis A virus: A new sanitary challenge

Author: Jean-Pierre Bronowicki, Cédric Hartard, Christophe Gantzer, Evelyne Schvoerer, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Jean Barriol (IJB), and Service d'Hépato-gastro-entérologie [CHRU Nancy]
Subjects: 0301 basic medicine, Genotype, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, Biology, medicine.disease_cause, Global Health, Genome, Communicable Diseases, Emerging, 03 medical and health sciences, Emerging pathogen, Liver disease, Hepatitis E virus, Virology, medicine, Humans, Geography, Medical, ComputingMilieux_MISCELLANEOUS, Carrier state, Incidence (epidemiology), Hepatitis A, Genetic Variation, medicine.disease, Hepatitis a virus, 3. Good health, Hepatitis E, Phylogeography, 030104 developmental biology, Infectious Diseases, Phenotype, Hepatitis A virus
Abstract: Hepatitis A (HAV) and E (HEV) viruses are able to cause liver disease in humans. Among the five classical hepatotropic viruses, they are mainly transmitted via the fecal-oral route. Historically, many similarities have thus been described between them according to their incidence and their pathogenicity, especially in countries with poor sanitary conditions. However, recent advances have provided new insights, and the gap is widening between them. Indeed, while HAV infection incidence tends to decrease in developed countries along with public health improvement, HEV is currently considered as an underdiagnosed emerging pathogen. HEV autochthonous infections are increasingly observed and are mainly associated with zoonotic transmissions. Extra hepatic signs resulting in neurological or renal impairments have also been reported for HEV, as well as a chronic carrier state in immunocompromised patients, arguing in favor of differential pathogenesis between those two viruses. Recent molecular tools have allowed studies of viral genome variability and investigation of links between viral plasticity and clinical evolution. The identification of key functional mutations in viral genomes may improve the knowledge of their clinical impact and is analyzed in depth in the present review.
Published: 2019
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22. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients

Author: Constance Delaugerre, Virginie Ferré, Anne Maillard, Vincent Calvez, Audrey Mirand, Anne-Geneviève Marcelin, Corinne Amiel, Julia Dina, Coralie Pallier, Hélène Le Guillou-Guillemette, Stéphanie Raymond, D. B. Fofana, Thomas Mourez, Hélène Jeulin, Samira Fafi-Kremer, Brigitte Montes, Pantxika Bellecave, Sophie Vallet, Thuy Van Nguyen, Diane Descamps, Catherine Roussel, Maxime Grude, Mary-Anne Trabaud, Charlotte Charpentier, Laurence Bocket, Philippe Flandre, Laura Le Guen, Anne Signori-Schmuck, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Toulouse [Toulouse], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Simulation et Traitement de l'information pour l'Exploitation des systèmes de Production (EDF R&D STEP), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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, Microbiologie Fondamentale et Pathogénicité (MFP), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, 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), CHU Clermont-Ferrand, CHU Lille, CHU Saint-Antoine [AP-HP], Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Saint Eloi (CHRU Montpellier), Service de Virologie [CHRU Nancy], CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Universitaire [Grenoble] (CHU), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Caen Normandie (UNICAEN), Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), 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 Saint-Eloi, Mzembaba, Sandy, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, MESH: Sequence Analysis, DNA, MESH: Treatment Failure, Aucun, Integrase inhibitor, HIV Infections, Drug resistance, MESH: HIV Seropositivity / drug therapy, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, HIV Seropositivity, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, biology, Elvitegravir, Middle Aged, Viral Load, 3. Good health, Integrase, MESH: HIV-1 / genetics, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Viral load, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Mutation, Genotype, MESH: HIV Integrase Inhibitors / therapeutic use, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: Drug Resistance, Multiple, Viral / genetics, MESH: HIV-1 / drug effects, 03 medical and health sciences, Drug Resistance, Multiple, Viral, Internal medicine, medicine, Humans, HIV Integrase Inhibitors, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, MESH: Viral Load / drug effects, MESH: Humans, business.industry, MESH: Adult, Sequence Analysis, DNA, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Regimen, chemistry, Mutation, HIV-1, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
Published: 2019
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23. Treatment as prevention enrolling at least 75% of individuals on ART will be needed to significantly reduce HIV prevalence in a HIV cohort

Author: Jean-Philippe Lanoix, Marialuisa Partisani, John M. Murray, Eliette Jeanmaire, Hélène Jeulin, Evelyne Schvoerer, Brice Malve, Laurent Hustache-Mathieu, Hugues Melliez, Marie André, Thierry May, François Goehringer, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], School of Mathematics and Statistics, University of New South Wales [Sydney] (UNSW), Cancer Council New South Wales (Cancer Council NSW), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Pathologies infectieuses et tropicales [CHU Amiens], CHU Amiens-Picardie, service de maladies infectieuses CHU J Minjoz Besancon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], and CHU Strasbourg
Subjects: 0301 basic medicine, Adult, Male, Unprotected Sexual Intercourse, 030106 microbiology, Human immunodeficiency virus (HIV), Emigrants and Immigrants, HIV Infections, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, Treatment status, Young Adult, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Prevalence, Medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, ComputingMilieux_MISCELLANEOUS, Sex Characteristics, Unsafe Sex, business.industry, Transmission (medicine), virus diseases, Middle Aged, Models, Theoretical, Treatment as prevention, Hiv prevalence, Antiretroviral therapy, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Patient Participation, business, Demography
Abstract: "Treatment as Prevention" (TasP) aims to reduce new HIV infections through higher enrolment on suppressive antiretroviral therapy (ART).We studied the current epidemic and possible impact of TasP in a French HIV cohort including MSM and migrant subjects.Socio-demographic, clinical and laboratory variables were collected during the follow-up of 6995 HIV-infected patients. The numbers of individuals living with HIV in each year were estimated from diagnoses up to that year minus recorded deaths. Patients were classified according to gender, transmission mode, country of birth and treatment status.The cohort includes 6995 individuals diagnosed from 1985 to 2015, of whom 72% were men. Unprotected sexual intercourse was the main mode of transmission. Women were more likely to be migrants (45% versus 13%), whereas men were more likely to have been born in France (52% versus 27%). Diagnoses were more correlated with untreated than treated prevalence in each group. MSM diagnoses was strongly correlated to untreated prevalence whatever the country of birth (p 0.0001). However, heterosexual diagnoses were better correlated with prevalence within individual country groups (b = 0.29 female diagnoses/year per untreated male born in France, compared to b = 0.73 for foreigners). Using these transmission rates, mathematical modelling estimated that enrolling 75% of untreated individuals per year would decrease diagnoses ten-fold by 2021.Enrolling at least 75% of individuals on ART is necessary to substantially impact numbers of new HIV infections in this cohort. Treatment as prevention will actually be effective to reduce HIV prevalence.
Published: 2019
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24. Impact of Cytomegalovirus Infection on the Outcome of Patients With Cirrhosis

Author: Faivre, Morgan, Cottet, Vanessa, Bour, Jean-Baptiste, Richou, Carine, Valmary-Degano, Séverine, Thiefin, Gerard, Andreoletti, Laurent, Geist, Claire, Schvoerer, Evelyne, Malve, Brice, Habersetzer, François, Fafi-Kremer, Samira, Binquet, Christine, Jouve, Jean-Louis, Bronowicki, Jean-Pierre, Doffoël, Michel, Hillon, Patrick, Herbein, Georges, Monnet, Elisabeth, Di Martino, Vincent, Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hépatogastroentérologie (CHU Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de virologie médicale [Reims], Hôpital Robert Debré, Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Service d'Hépato-gastro-entérologie [CHRU Nancy], Service d’Hépatogastroentérologie, NHC, CHU de Strasbourg, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Service d'Anatomie pathologique [CHRU Besançon]
Subjects: [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical aspects, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cirrhosis and its complications, digestive system diseases, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Goals: The aims of this study were to evaluate whether cytomegalovirus (CMV) infection is associated with hepatocellular carcinoma (HCC) and liver-related mortality in cirrhotic patients.Background: In cirrhotic patients, the determinants of HCC and liver-related death are imperfectly known. CMV infection, by its prooncogenic and proinflammatory properties, may favor both the development of HCC and deleterious systemic inflammation.Study: In the 1178 patients included between June 2008 and December 2012 in the CIrrhose et Risque de Carcinome Hépatocellulaire dans le grand-Est (CIRCE) study, a French multicenter case-control study designed to identify risk factors of HCC among cirrhotic patients, we identified 432 patients with interpretable CMV serological status at baseline. They included 159 cases with HCC and 273 controls. We measured factors associated with HCC at baseline and subsequent HCC in controls, and predictors of overall and liver-related death in the whole study population.Results: During a median follow-up of 31 months, 25 cases of HCC developed in controls, and 209 deaths (163 liver-related) were recorded. There were 247 (57.2%) CMV-seropositive patients. CMV seropositivity was not associated with more frequent HCC at baseline or during follow-up, but among CMV-positive patients with HCC, the proportion of multinodular, infiltrative, or metastatic tumors at diagnosis was higher (73.8% vs. 57.3%; P=0.029), inducing higher mortality (74% vs. 52% at 3 years; P=0.004). By Cox-regression adjusted for age, gender, Model for End-stage Liver Disease (MELD) score, HCC at baseline, and diabetes, CMV seropositivity independently predicted all-cause (hazard ratio=1.45; 95% confidence interval, 1.08-1.94; P=0.013) and liver-related mortality (hazard ratio=1.56; 95% confidence interval, 1.04-2.30; P=0.031).Conclusions: In this preliminary study, CMV-seropositive cirrhotic patients were at higher risk of liver-related death caused by more aggressive HCCs or severe cirrhosis complications. These findings warrant confirmation.
Published: 2019
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25. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France

Author: Gilles Peytavin, Mary-Anne Trabaud, Anne Signori-Schmuck, Charlotte Charpentier, Marc Wirden, Cécile Henquell, Laurence Bocket, Catherine Delamare, Samira Fafi-Kremer, Jacques Izopet, Chakib Allaoui, Georges Dos Santos, A. Beby-Defaux, Benoit Visseaux, Virginie Ferré, Coralie Pallier, Diane Descamps, Stéphanie Marque-Juillet, Lambert Assoumou, Magali Bouvier-Alias, Sophie Vallet, Alexis de Rougemont, Hélène Le Guillou-Guillemette, Vincent Calvez, Stéphanie Raymond, Corinne Amiel, Honorine Fenaux, Anne De Monte, Francis Barin, Anne Krivine, Véronique Avettand-Fenoel, Annick Allardet-Servent, Jean-Christophe Plantier, Rachid Ait-Namane, Laurence Morand-Joubert, Marie-Laure Chaix, Camille Tumiotto, Maxime Grude, Anne Maillard, Laurence Courdavault, Brigitte Montes, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Avicenne [AP-HP], CHU Clermont-Ferrand, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de la Martinique [Fort de France], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [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), CHU Bordeaux [Bordeaux], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Victor Dupouy, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Mzembaba, Sandy, Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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, Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Argenteuil (CH Argenteuil), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Paris Descartes, Sorbonne Paris Cité, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and ANRS – France REcherche Nord&Sud Sida-hiv Hépatites
Subjects: 0301 basic medicine, Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], Integrase inhibitor, hiv, HIV Infections, Drug resistance, MESH: HIV-1 / genetics, MESH: Genotype, MESH: HIV Infections / epidemiology, 0302 clinical medicine, Genotype, Blood plasma, HIV Seropositivity, rna-directed dna polymerase, Prevalence, rna, Pharmacology (medical), 030212 general & internal medicine, MESH: Chronic Disease / epidemiology, ComputingMilieux_MISCELLANEOUS, cd4 count determination procedure, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, anti-retroviral agents, MESH: France / epidemiology, Antiinfective agent, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Drug Resistance, Viral / genetics, 3. Good health, endopeptidases, [SDV] Life Sciences [q-bio], integrase inhibitors, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: RNA, Viral / blood, Female, France, MESH: HIV Seropositivity / epidemiology, Microbiology (medical), Adult, medicine.medical_specialty, peptide hydrolases, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / classification, MESH: HIV-1 / drug effects, Virus, MESH: HIV Infections / transmission, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, viruses, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, plasma, safe sex, MESH: Prevalence, Pharmacology, drug resistance, MESH: Humans, business.industry, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, CD4 Lymphocyte Count, MESH: Anti-HIV Agents / therapeutic use, Chronic Disease, Mutation, HIV-1, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages.
Published: 2018
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26. Molecular features of Hepatitis E Virus circulation in environmental and human samples

Author: Manon Chassaing, Christophe Gantzer, Jean-Pierre Bronowicki, A. Gentilhomme, Hélène Jeulin, Honorine Fenaux, Sébastien Berger, Isabelle Bertrand, Evelyne Schvoerer, M. Bensenane, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hépato-gastro-entérologie [CHRU Nancy], and Institut Jean Barriol (IJB)
Subjects: Adult, Male, 0301 basic medicine, Antigenicity, Genotype, Swine, viruses, Sus scrofa, 030106 microbiology, Viral quasispecies, Biology, medicine.disease_cause, Feces, Viral Proteins, 03 medical and health sciences, Hepatitis E virus, Virology, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Swine Diseases, Hepatitis, Molecular Epidemiology, Sewage, Molecular epidemiology, virus diseases, Sequence Analysis, DNA, Middle Aged, medicine.disease, Hepatitis E, [SDE.ES]Environmental Sciences/Environmental and Society, 3. Good health, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France
Abstract: Background and objectives Hepatitis E virus (HEV) is emerging but its circulation between humans and the environment remains misunderstood. HEV ORF2 gene encodes the capsid playing a key role in viral interactions with surfaces, ORF3 products are involved in the viral cycle. Our aim was to study the molecular characteristics of ORF2 and ORF3 which could favor HEV fitness in patients and the environment. Study design Samples from 69 patients with hepatitis (blood/stools), 20 urban wastewaters, 20 effluents of a pig slaughterhouse, 22 farm pigs (stools), 20 wild boars (liver/stools) were collected in North-Eastern France. HEV strains were analyzed by direct sequencing within the ORF2 M region, of ORF2/ORF3, for phylogeny and physicochemical prediction and for ORF2 by ultra-deep sequencing. Results The results showed frequent HEV-positive samples: 9.1% of the patient bloods, 23.1% of their stools; 25.0% of wastewaters, 75.0% for the slaughterhouse, 10.0% of the boar livers, 5.3% of their stools. The strains were classified as HEV genotype 3. In ORF2, HEV highlighted one homogeneous major viral variant within quasispecies and a decrease in predicted antigenicity for two minor mutations (D442G, V402A). A cysteine signature at position 81 in ORF3 was observed in the boars. Conclusions HEV RNA genotype 3 was detected in patients and in animals, in a slaughterhouse effluent and in wastewater. Moreover, the low variability of amino acids in the ORF2 M region and molecular features in ORF2 and ORF3 suggested that HEV strains could be advantageous for key properties.
Published: 2018
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27. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Author: Raymond, E, Nicot, F., Morand-Joubert, A, Rodallec, D, Mourez, M, Beby-Defaux, D, Lambert-Niclot, P, Charpentier, E, Malvé, B., Le Guillou-Guillemette, A, Si-Mohamed, D, Avettand Fenoel, A, Roussel, A., Calvez, P, Saune, E, Rodriguez, M, Descamps, E, Izopet, E, Lagier, E, Roussel, C, Le Guillou-Guillemette, G, Alloui, A., Bettinger, D., Pallier, P, Fleury, Frédéric, Reigadas, R, Bellecave, P., Recordon-Pinson, P, Payan, P, Vallet, S., Vabret, A., Dina, D, Henquell, C., Mirand, A., Bouvier-Alias, A, de Rougemont, A, Dos Santos, D, Morand, P, Signori-Schmuck, A., Bocket, B, Rogez, R, Andre, A, Tardy, C, Trabaud, A, Tamalet, C., Delamare, D, Montes, B, SCHVOERER, Evelyne, Ferré, F., André-Garnier, E., Cottalorda, C, Guinard, G, Guiguon, A, Descamps, D., Brun-Vézinet, B, Charpentier, c, Visseaux, B, Peytavin, G., Krivine, A., Si-Mohamed, A, Avettand-Fenoel, Véronique, Marcelin, A, Calvez, C, Lambert-Niclot, L, Soulié, C., Wirden, M., Morand-Joubert, M, Delaugerre, D, Chaix, M, Amiel, A, Schneider, S., Giraudeau, G, Beby- Defaux, D, Brodard, B, Maillard, A., Plantier, P, Chaplain, C, Bourlet, B, Fafi-Kremer, F, Stoll-Keller, F., Schmit, P, Barth, B, Yerly, S, Poggi, P., Izopet, I, Raymond, R, Barin, B, Chaillon, A, Marque-Juillet, M, Roque-Afonso, A, Haïm-Boukobza, B, Flandre, P., Grudé, G, Assoumou, A, Costagliola, D, Allegre, A, Schmit, J, Chennebault, M, Bouchaud, B, Magy-Bertrand, B, Delfraissy, D, Dupon, D, Morlat, P, Neau, D, Ansart, A., Jaffuel, J, Verdon, R, Jacomet, C, Lévy, L, Dominguez, D, Chavanet, P., Piroth, P, Cabié, A., Leclercq, P, Ajana, A, Cheret, A, Weinbreck, P, Cotte, C, Poizot-Martin, P, Ravaud, R., Christian, B, Truchetet, F, Grandidier, G, Rey, R., May, M, Goehringer, G, Raffi, F., Dellamonica, D, Prazuck, P, Hocqueloux, L, Landman, R, Yazdanpanah, Y., Launay, L, WEISS, L, Viard, P, Katlama, C., Simon, A., Girard, G, Meynard, M, Molina, M, Pialoux, G, Hoen, B., Goeger-Sow, G, Lamaury, I, Beaucaire, G, Le Moal, G., Jaussaud, R., Rouger, C, Michelet, M., Borsa-Lebas, B, Caron, F, Khuong, A., Lucht, F., Rey, D., Calmy, A, Lafeuillade, A, Marchou, B, Delobel, D, Gras, G, Greder-Belan, A, Vittecoq, D, Teiche, E, 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), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de virologie [CHU Toulouse], CHU Toulouse [Toulouse], Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universiatire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Rouen, Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Henri Mondor, CHU Pitié-Salpêtrière [AP-HP], 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), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Virologie [AP-HP Hôpital Bichat-Claude-Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Clermont-Ferrand, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Necker, Centre Hospitalier Universitaire d'Amiens, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Agence Nationale de Recherches sur le SIDA et les hepatites virales (French National Agency for Research on AIDS and Viral Hepatitis, ANRS), Janssen-Cilag SAS, Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Pharmacologie Médicale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Faculté de Médecine/CHU, CHU Besançon, Université de Franche-Comté (UFC), Génétique et évolution des interactions hôtes-parasites, Département génétique, interactions et évolution des génomes [LBBE] (GINSENG), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Virologie Humaine et Moléculaire [Caen], Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), 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), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Necker - Enfants Malades [AP-HP], Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AgroParisTech, T1, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences pour l'environnement (SPE), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Département d'infectiologie (CHU de Dijon), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire d'Acoustique de l'Université du Mans (LAUM), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), ONERA - The French Aerospace Lab [Toulouse], ONERA, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), UMR CNRS 8179, Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales (POTIERS - Mal Inf), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Maladies Infectieuses et Tropicales [CHU Poitiers], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital de la Pitié-Salpêtrière, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Male, Drug Resistance, HIV Infections, Drug resistance, Medical and Health Sciences, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2.1 Biological and endogenous factors, Viral, Aetiology, Articles and Commentaries, ComputingMilieux_MISCELLANEOUS, minority resistant variants, Viral Load, Biological Sciences, first-line antiretroviral therapy, 3. Good health, Infectious Diseases, Rilpivirine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV/AIDS, Female, Infection, Viral hepatitis, Viral load, Microbiology (medical), Adult, ultra-deep sequencing, Microbiology, Virus, rilpivirine, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Drug Resistance, Viral, Genetics, medicine, Humans, business.industry, Genetic Variation, medicine.disease, Virology, Reverse transcriptase, Regimen, Good Health and Well Being, 030104 developmental biology, chemistry, Mutation, HIV-1, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, Antimicrobial Resistance, business
Abstract: Background Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR). Methods All the subjects, 541 HIV-1–infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load Results NGS revealed resistance-associated mutations accounting for 1% to 20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count Conclusions Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.
Published: 2018
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28. The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection

Author: M. Bensenane, Thierry May, Honorine Fenaux, Fabien Zoulim, Evelyne Schvoerer, Brice Malve, Jean-Pierre Bronowicki, François Goehringer, Sibel Berger, Aurélie Velay, Hélène Jeulin, Jean-Pol Frippiat, Marine Eschlimann, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Virology Laboratory, General Hospital Papageorgiou, Virus des hépatites et pathologies associées, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Service de Virologie [CHRU Nancy]
Subjects: 0301 basic medicine, Adult, Male, Antigenicity, HBsAg, Hepatitis B virus, Genotype, HIV Infections, medicine.disease_cause, Persistence (computer science), Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Viral Envelope Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Sequence Deletion, Mutation, Hepatitis B Surface Antigens, business.industry, Coinfection, Haplotype, virus diseases, Hepatitis B, Middle Aged, Viral Load, medicine.disease, digestive system diseases, 3. Good health, Chronic infection, 030104 developmental biology, Infectious Diseases, Immunology, DNA, Viral, 030211 gastroenterology & hepatology, business
Abstract: Background More than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3–16%). Objectives HBV envelope variability was investigated according to HBsAg persistence. Study design The cohort consisted of 15 HBV genotype A-infected patients divided into “resolvers”, with HBsAg clearance, and “non-resolvers”, with HBsAg persistence and in subgroups: acute (n = 5, AHBV) or chronic infection (n = 4, CHBV) and HBV/HIV coinfection (n = 6, CHBV/HIV). HBV S and preS sequences were studied by direct and ultra-deep sequencing. Amino acid sequences were analyzed with bioinformatics for predicted antigenicity. Results In S gene, the complexity was lower in AHBV than in chronic-infected patients (p = 0.046). Major mutations, detected using direct sequencing, were more frequent in AHBV developing chronicity (p = 0.01) than in AHBV resolvers. In the Major Hydrophilic Region, more frequent mutations were observed in non-resolvers versus resolvers (p = 0.047) and non-resolvers tended to have more haplotypes with a reduced predicted antigenicity (p = 0.07). Most of the mutations in preS/S region were found rather in epitopic than in non-epitopic areas (p = 0.025). Interestingly, the mutation sY161F found in 3/8 non-resolvers was associated with a decrease in predicted antigenicity (28%; AnTheProt). Conclusions HBsAg persistence was correlated with mutations and deletions in areas playing a key role in immune recognition. These data suggest that variability in HBV envelope could favor immune escape in various clinical settings of HBV genotype A-infected patients.
Published: 2017
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29. Impact of deletions and mutations in Hepatitis B virus envelope proteins on serological profile and clinical evolution

Author: Marine Eschlimann, Hélène Jeulin, Shaunagh Galgey, Honorine Fenaux, Thierry May, Evelyne Schvoerer, Christian Rabaud, Fabien Zoulim, Brice Malve, François Goehringer, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], and Service de Virologie [CHRU Nancy]
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, HBsAg, Hepatitis B virus, Epitopes, T-Lymphocyte, Biology, medicine.disease_cause, Epitope, Hepatitis B virus PRE beta, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, Antigen, Viral envelope, Viral entry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Humans, Selection, Genetic, Sequence Deletion, chemistry.chemical_classification, Hepatitis B Surface Antigens, Virulence, Middle Aged, 3. Good health, 030104 developmental biology, Infectious Diseases, chemistry, Immunology, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epitopes, B-Lymphocyte, 030211 gastroenterology & hepatology, Glycoprotein
Abstract: International audience; The Hepatitis B virus (HBV) envelope glycoproteins are essential for viral entry into the hepatocyte and are also targets for host immune response. The study of these proteins could allow us to highlight molecular hot points influencing HBV fitness, which would subsequently modify the clinical evolution of the disease, both under anti-viral therapy or without treatment. The present short communication underlines the importance of the high variability in HBV envelope proteins, in regard with the literature and in our hands, for HBV-infected patients either on anti-HBV treatment or not. We report mutations in antigenic areas of S protein, i.e. CD8+/CD4+ T-cell epitopes and B-cell epitopes in the major hydrophilic region (MHR), such as sI126N and sG145R possibly involved in the rare coexisting Hepatitis B surface Antigen (HBsAg)/anti-HBs serological pattern. We mostly report serial mutations in preS region including preS1 deletion (aa 1-6, 31-71, 38-73, 72-104) and preS2 deletion (aa132-141) in patients with various clinical evolutions. Some of these viral envelope mutations, due to immune selection pressure, may result in a worsening of the hepatic disease.
Published: 2017
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30. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

Author: Yingying Wang, Chongsheng Qian, Bénédicte Bruno, Isabelle Clerc Urmes, Huili Cai, Patrice Ceballos, Cécile Pochon, Jean Hugues Dalle, Arnaud Campidelli, Marcelo De Carvalho Bittencourt, Nadine Petitpain, Danièle Bensoussan, Maud D'Aveni, Catherine Paillard, Hélène Jeulin, Loïc Reppel, Charlotte Jubert, Clément Cholle, Aude Marie-Cardine, Véronique Decot, Stephane Vigouroux, Claire Galambrun, Véronique Venard, Alexandra Salmon, Laurence Clement, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Unité de Thérapie Cellulaire et Tissulaire [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie [CHRU Nancy], Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hôpital Jeanne de Flandre [Lille], Hôpital de Hautepierre [Strasbourg], Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Nicolle [Rouen], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Faculté de Pharmacie [Nancy], and Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, Graft vs Host Disease, T-Cell Antigen Receptor Specificity, Hematopoietic stem cell transplantation, Immunotherapy, Adoptive, Adenovirus Infections, Human, 0302 clinical medicine, T-Lymphocyte Subsets, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Diseases of the blood and blood-forming organs, Hematology, Viral Load, Allografts, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tissue Donors, 3. Good health, Treatment Outcome, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Interferon-γ-based immunomagnetic isolation, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, Viral load, Immunosuppressive Agents, Adult, Third party haploidentical donor, medicine.medical_specialty, Adolescent, T cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:RC254-282, Interferon-gamma, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Leukapheresis, Viremia, Adenovirus infection, Molecular Biology, Umbilical cord blood transplantation, Immunomagnetic Separation, lcsh:RC633-647.5, business.industry, Umbilical Cord Blood Transplantation, Research, Adenoviruses, Human, medicine.disease, Allogeneic stem cell transplantation, Transplantation, 030104 developmental biology, Graft-versus-host disease, Transplantation, Haploidentical, Immunology, Virus Activation, Adenovirus-specific T cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered). Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.
Published: 2017
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31. Impact of Cytomegalovirus infection on the outcome of patients with cirrhosis: a preliminary study

Author: Jean-Baptiste Bour, Laurent Andreoletti, Vanessa Cottet, Jean-Louis Jouve, J.-J. Raabe, Elisabeth Monnet, Gérard Thiéfin, Samira Fafi-Kremer, Morgan Faivre, Séverine Valmary-Degano, Georges Herbein, François Habersetzer, Michel Doffoel, Brice Malve, Hélène Barraud, V. Di Martino, Evelyne Schvoerer, Jean-Pierre Bronowicki, Christine Binquet, C. Richou, Patrick Hillon, Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz [Besançon], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Unité de virologie médicale [Reims], Hôpital Robert Debré, Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Laboratoire de Virologie [Strasbourg], Service d'Ophtalmologie (CHU de Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie ( CIC-P803 ), Université de Bourgogne ( UB ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Service d'hépato-gastroentérologie, CHU Strasbourg-Hopital Civil, Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Service d'hépatogastroentérologie (CHU Reims), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Anatomie pathologique [CHRU Besançon], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: Clinical aspects, Cirrhosis and its complications, 0303 health sciences, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Clinical aspects, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Gastroenterology, Outcome (game theory), 3. Good health, Cytomegalovirus infection, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cirrhosis and its complications, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2017
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32. Hepatitis E virus emergence in north eastern France

Author: Fenaux, Honorine, Chassaing, Manon, Berger, Sibel, Jeulin, H., Bensenane, Mouni, Bronowicki, Jean-Pierre, Gantzer, C., Bertrand, Isabelle, SCHVOERER, Evelyne, Bertrand, Isabelle, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Service d'Hépato-gastro-entérologie [CHRU Nancy]
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

33. Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient

Author: Mory S, Marie-Reine Losser, Ladriere M, Velay A, Feugeas J, Pertek Jp, Hélène Jeulin, Université de Lorraine (UL), Service d'Anesthésiologie et de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie [CHRU Nancy], Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service de Néphrologie [CHRU Nancy], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Adult, 0301 basic medicine, Hepatitis, Viral, Human, viruses, 030106 microbiology, Herpesvirus 1, Human, Herpes simplex virus, Healthcare-associated infections, medicine.disease_cause, Hepatitis, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, Cross Infection, biology, medicine.diagnostic_test, business.industry, Herpes Simplex, medicine.disease, Kidney Transplantation, 3. Good health, Polymerase chain reaction, Transplantation, Solid organ transplant, Infectious Diseases, medicine.anatomical_structure, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver biopsy, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, Pancreas Transplantation, Antibody, Pancreas, Complication, business
Abstract: International audience; Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.
Published: 2016
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34. Optimising the diagnostic strategy for onychomycosis from sample collection to FUNGAL identification evaluation of a diagnostic kit for real-time PCR

Author: Anne Debourgogne, Dimitri Petinataud, Nelly Contet-Audonneau, Sibel Berger, Marie Machouart, Cyril Ferdynus, Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie [CHRU Nancy], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Stress, Immunité, Pathogènes (SIMPA), and Université de Lorraine (UL)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Time Factors, Sample (material), 030106 microbiology, Direct examination, Culture, Medical laboratory, Dermatology, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Specimen Handling, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Onychomycosis, Diagnosis, Humans, Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, DNA, Fungal, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Retrospective Studies, biology, business.industry, Arthrodermataceae, Fungi, Kit, General Medicine, Diagnostic strategy, biology.organism_classification, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, PCR, Female, Identification (biology), Reagent Kits, Diagnostic, Sample collection, business
Abstract: International audience; Onychomycosis is a common nail disorder mainly due to dermatophytes for which the conventional diagnosis requires direct microscopic observation and culture of a biological sample. Nevertheless, antifungal treatments are commonly prescribed without a mycological examination having been performed, partly because of the slow growth of dermatophytes. Therefore, molecular biology has been applied to this pathology, to support a quick and accurate distinction between onychomycosis and other nail damage. Commercial kits are now available from several companies for improving traditional microbiological diagnosis. In this paper, we present the first evaluation of the real-time PCR kit marketed by Bio Evolution for the diagnosis of dermatophytosis. Secondly, we compare the efficacy of the kit on optimal and non-optimal samples. This study was conducted on 180 nails samples, processed by conventional methods and retrospectively analysed using this kit. According to our results, this molecular kit has shown high specificity and sensitivity in detecting dermatophytes, regardless of sample quality. On the other hand, and as expected, optimal samples allowed the identification of a higher number of dermatophytes by conventional mycological diagnosis, compared to non-optimal samples. Finally, we have suggested several strategies for the practical use of such a kit in a medical laboratory for quick pathogen detection.
Published: 2016
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35. Evaluation of Virological Microparticle Enzyme Immunoassay According to the ISO 15189: Real-Life Experience in a University Hospital

Author: Aurélie Velay, Christine Prin-Mathieu, Evelyne Schvoerer, Hélène Jeulin, Sophie Lafontaine, Odette Agulles, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Virology Laboratory, General Hospital Papageorgiou, Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 030213 general clinical medicine, medicine.medical_specialty, ISO 15189, education, MEDLINE, HIV Core Protein p24, MESH: Accreditation, Immune markers, Microparticle Enzyme Immunoassay, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, Accreditation, Hospitals, University, Immunoenzyme Techniques, 03 medical and health sciences, 0302 clinical medicine, MESH: Laboratories, Hospital, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Humans, Medical physics, Intensive care medicine, MESH: Immunoenzyme Techniques, MESH: Hospitals, University, Hepatitis B Surface Antigens, MESH: Humans, MESH: HIV Core Protein p24, business.industry, Architect i2000sr, University hospital, Laboratories, Hospital, 3. Good health, MESH: Hepatitis B Surface Antigens, Serology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Validation of Methods, business
Abstract: The International Standard ISO 15189 based on the ISO 9001:2008 emphasizes specific requirements for quality and ability of medical laboratories. The accreditation of medical laboratories according to ISO 15189 includes the validation of biological methods, which depends on collection of bibliographic data and experimental proofs. Moreover, these results must be compared to provider data sheets and independent scientific data. In the immunodiagnostic field, independent published data are deeply lacking. The aim of our work was to share experience of method validation for virological immune markers on the widely used Architect i2000sr.After risk analysis, intra- and inter-assay variability, and inter-sample contamination were evaluated for each method, and sensitivity was investigated for antigen detection tests. A comparison between the two Architect i2000sr available in our laboratory was also performed.All tested methods were consistent with the manufacturer data (from the data sheet). No inter-sample contamination was observed. Both devices are broadly equivalent and can be used indifferently or as a backup solution of the other.To our knowledge, those results are the first independent complete data on the reliability of the Architect i2000sr in real-life experience. These data are needed to the accreditation of our platform and potentially useful for the accreditation of other laboratories using the same equipment.
Published: 2016
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36. BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease

Author: Oussalah, Abderrahim, Avogbe, Patrice Hodonou, Guyot, Erwan, Chery, Céline, Guéant, Rosa-Maria, Ganne-Carrié, Nathalie, Cobat, Aurélie, Moradpour, Darius, Nalpas, Bertrand, Negro, Francesco, Poynard, Thierry, Pol, Stanislas, Bochud, Pierre, Abel, Laurent, Jeulin, Hélène, Schvoerer, Evelyne, Chabi, Nicodème, Amouzou, Emile, Sanni, Ambaliou, Barraud, Hélène, Rouyer, Pierre, Josse, Thomas, Goffinet, Laetitia, Jouve, Jean-Louis, Minello, Anne, Bonithon-Kopp, Claire, Thiefin, Gérard, Di Martino, Vincent, Doffoël, Michel, Richou, Carine, Raab, Jean-Jacques, Hillon, Patrick, Bronowicki, Jean-Pierre, Guéant, Jean-Louis, Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Paris 13 ( UP13 ), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP), Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lausanne ( UNIL ), Département d'hépatologie [CHU Cochin], Institut Pasteur [Paris]-CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Hydrogéologie et de Géothermie [Neuchâtel] ( CHYN ), Université de Neuchâtel ( UNINE ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Sorbonne Université, Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), The Rockefeller University [New-York], Université de Lorraine ( UL ), Laboratoire de Virologie [Strasbourg], Université de Kara, University of Abomey Calavi ( UAC ), Service d'Hépato-gastro-entérologie [CHRU Nancy], Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), CHU Strasbourg, Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), This study was supported by a French Government grant managed by the French National Research Agency under the program 'Investissements d’Avenir', reference ANR-11-LABX-0021 and also by the Institut National du Cancer (INCA), the French regions of Lorraine and Burgundy, the Ligue Nationale contre le Cancer (CiRCE-Nutrigenex), the European Regional Development Fund, the Canceropole Grand-Est, and the Fondation de France.The ANRS Study HC EP 26 Genoscan group is supported by the National Agency for Research on AIDS and Viral Hepatitis (ANRS).The Swiss Hepatitis C Cohort Study (SCCS) is supported by grants from the Swiss National Science Foundation (3347C0-108782/1), the Swiss Federal Office for Education and Sciences (03.0599) and the European Commission (LSHM-CT-2004-503359, VIRGIL Network of Excellence on Antiviral Drug Resistance). The SCCS genetic project is supported by the Leenaards foundation, the Santos-Suarez foundation and the Swiss National Science Foundation (324730-144054), ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du ( 2011 ), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris 13 (UP13), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Hydrogéologie et de Géothermie [Neuchâtel] (CHYN), Université de Neuchâtel (UNINE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Rockefeller University [New York], Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), University of Abomey Calavi (UAC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), CiRCE Study Group, Hôpital Jean Verdier, Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'hépathologie [CHU Cochin], Université de Neuchâtel, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université d'Abomey Calavi, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Subjects: hepatitis C virus, BRIP1, DNA repair genes, hepatitis B virus, hepatocellular carcinoma, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Research Paper, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract: IF 5.008; International audience; The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.
Published: 2016
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37. Occult hepatitis B infection in patients infected with HIV: Report of two cases of hepatitis B reactivation and prevalence in a hospital cohort

Author: H. Jeulin, C. Burty, V. Venard, C. Rabaud, L. Letranchant, B. Bloquel, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
Subjects: Adult, Male, Hepatitis B virus, Adolescent, Anti-HIV Agents, [SDV]Life Sciences [q-bio], HIV Infections, medicine.disease_cause, Serology, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Orthohepadnavirus, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Virology, Prevalence, medicine, Humans, 030212 general & internal medicine, Hepatitis B Antibodies, Child, ComputingMilieux_MISCELLANEOUS, Aged, 0303 health sciences, biology, 030306 microbiology, business.industry, virus diseases, Middle Aged, Hepatitis B, biology.organism_classification, medicine.disease, Hospitals, digestive system diseases, 3. Good health, Infectious Diseases, Hepadnaviridae, DNA, Viral, Immunology, Female, Virus Activation, Viral disease, business, Viral load
Abstract: Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are particularly at risk of hepatitis B reactivation. Two cases of patients infected with HIV with isolated anti-HBc antibodies who had experienced an HBV reactivation are described. In the two cases HBV reactivation occurred after withdrawal of anti-retroviral treatment with anti-HBV activity from the patients' highly active antiretroviral therapy (HAART), in accordance with HIV genotypic resistance profiles. Consequently, plasma samples from 383 patients infected with HIV were tested to assess the prevalence of occult HBV infection in the Infectious Diseases Department Unit of Nancy Hospital by investigating serological patterns and HBV replication. Forty-five percent (172/383) of patients had had previous contact with HBV. Isolated anti-HBc antibodies were observed in 48 patients (48/383, 12%) and, among these, 2 were HBV-DNA positive. Since 75% (288/383) of the patients were treated with HAART, including at least one drug active against HBV, occult HBV infection was perhaps unrecognized. In cases of HIV infection, all patients should be screened for HBV infection and the knowledge of HBV status as well as the monitoring of HBV viral load are essential in preventing HBV reactivation. Consideration should be given to the continuation of drugs with anti-HBV activity in co-infected patients receiving HAART, as cessation of therapy is associated with a risk of HBV reactivation. At least, close monitoring of the HBV viral load is warranted in such situations. J. Med. Virol. 82:206–212, 2010. © 2009 Wiley-Liss, Inc.
Published: 2010
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38. Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity

Author: Ducancelle, Alexandra, Pivert, Adeline, Bertrais, Sandrine, Boursier, Jérôme, Balan, Viorica, Veillon, Pascal, Le Guillou-Guillemette, Hélène, Thibault, Vincent, Castelain, Sandrine, Roquebert, Bénédicte, Coste-Burel, Marianne, Mackiewicz, Vincent, Schvoerer, Evelyne, Larrat, Sylvie, Maylin, Sarah, Alain, Sophie, Loustaud-Ratti, Véronique, Gordien, Emmanuel, Gozlan, Joël, Brodard, Véronique, Chevaliez, Stéphane, Calès, Paul, Lunel-Fabiani, Françoise, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire de virologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Unité de Virologie clinique et fondamentale (UVCF), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: PC mutation, Adult, Liver Cirrhosis, Male, Hepatitis B virus, HBV genotype, Severity of Illness Index, BCP mutation, Hepatitis B, Chronic, Sex Factors, G1896A, Risk Factors, A1762T/G1764A, Humans, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, Aged, Hepatitis B Surface Antigens, Virulence, fibrosis, Age Factors, Middle Aged, Hepatitis B, G1899A, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, DNA, Viral, Mutation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female
Abstract: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis.Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region.The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028).Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.
Published: 2015
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39. Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy

Author: Marine Eschlimann, J. P. Bronowicki, John M. Murray, Priya Abraham, Brice Malve, Aurélie Velay, Jean-Pol Frippiat, Evelyne Schvoerer, M. Bensenane, Christophe Combet, François Goehringer, Fabien Zoulim, Hélène Jeulin, Ashrafali M. Ismail, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service d'Hépato-gastro-entérologie [CHRU Nancy], Christian Medical College & Hospital, University of New South Wales [Sydney] (UNSW), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, HBsAg, Mutant, medicine.disease_cause, Persistence (computer science), 0302 clinical medicine, Medicine, S variability, Mice, Inbred BALB C, Nucleotides, virus diseases, Nucleosides, Middle Aged, Antigenic Variation, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Hepatitis B Virus, Adult, Antigenicity, HBV preS, Enzyme-Linked Immunosorbent Assay, Anti-HBV treatment, Antiviral Agents, 03 medical and health sciences, Hepatitis B, Chronic, Virology, Genetic variation, Antigenic variation, Animals, Humans, Gene, Aged, Hepatitis B virus, Hepatitis B Surface Antigens, Hepatology, business.industry, Computational Biology, Genetic Variation, Sequence Analysis, DNA, digestive system diseases, 030104 developmental biology, Amino Acid Substitution, Immunology, Mutant Proteins, business
Abstract: International audience; For hepatitis B virus (HBV)-related chronic infection under treatment by nucleos(t)ide analogues (NUCs), HBsAg clearance is the ultimate therapeutic goal but very infrequent. We investigated how HBV envelope protein variability could lead to differential HBsAg clearance on NUCs. For 12 HBV genotype D patients receiving NUCs, six resolvers (HBsAg clearance) were compared to six matched nonresolvers (HBsAg persistence). PreS/S amino acid (aa) sequences were analysed with bioinformatics to predict HBV envelope antigenicity and aa covariance. To enrich our analyses on very rare resolvers, these were compared with other HBV genotype D strains in three characterized clinical cohorts including common chronically infected patients. The sT125M+sP127T combination was observed in four nonresolvers of six, corroborated by aa covariance analysis, associated with a lower predicted antigenicity than sT125T+sP127P. Concordant features within this HBV key functional domain, at positions 125 and 127, were reported from two of the three comparative cohorts. In our hands, a lower ELISA reactivity of HBV-vaccinated mice sera was observed against the sT125M mutant. In the S gene, 56 aa changes in minor variants were detected in non-resolvers, mainly in the major hydrophilic region, vs 28 aa changes in resolvers. Molecular features in patients showing HBsAg persistence on NUCs argue in favour of a different aa pattern in the HBV S gene compared to those showing HBsAg clearance. In nonresolvers, a decrease in HBs a' determinant antigenicity and more frequent mutations in the S gene suggest a role for the HBV envelope characteristics in HBsAg persistence.
Published: 2015
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40. HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007–12: impact on susceptibility to first-line strategies

Author: Frange, Pierre, Assoumou, Pierre, Descamps, Diane, Chéret, Antoine, Goujard, Cécile, Tran, Laurent, Gousset, Marine, Avettand-Fenoël, Véronique, Bocket, Laurence, Tran, Samira, Guinard, Jérôme, Morand-Joubert, Pierre, Nicot, Florence, Plantier, Jean-Christophe, Rogez, Sylvie, Wirden, Pierre, Rouzioux, Christine, Meyer, Laurence, Chaix, Marie-Laure, Abel, S., Abraham, B., Antoniotti, A., Armero, R., Audhuy, B., Aumaitre, H., Beaucaire, G., Beck-Wirth, G., Berger, J.L., Bernard, L., Beuscart, C., Bodard, L., Bouchaud, O., Boue, F., Cabane, J.-P., Cabié, A., Champagne, H., Cheneau, C., Chennebault, J.-M., Cheret, A., Christian, B., Compagnucci, A., Daneluzzi, V., Debab, Y., Dellamonica, P., Delfraissy, F., Devidas, A., Diab, G., Doll, J., Drobacheff-Thebaut, C., Durel, A., Esnault, L., Faba, L., Froguel, E., Garipuy, D., Garrait, V., Geffray, L., Genet, C., Genet, P., Gérard, L., Ghosn, J., Girard, J., Girard, Pascal, Godin-Collet, C., Hochedez, P., Hoen, B., Houlbert, D., Jacomet, C., Jeantils, V., Jidar, K., Klement, E., Lafeuillade, A., Launay, V., Leprêtre, A., Levy, Y., Makhloufi, D., Malbec, D., Martha, B., May, T., Merrien, D., Miailhes, P., Miodovski, C., Morlat, P., Mortier, E., Neau, D., Obadia, M., Patey, O., Pellegrin, L., Perronne, V., Philibert, P., Pialoux, G., Pichancourt, G., Piroth, L., Poinsignon, Y., Poizot-Martin, I., Prazuck, T., Prendki, V., Du Clary, F., Quinsat, D., Regnier, A., Reynes, J., Rosenthal, E., Rouveix, E., Salmon, D., Salanville, F., Schmitt, L., Simon-Coutellier, A., Sotto, A., Souala, F., Stein, A., Timsit, F., de Truchis, P., Uludag, A., Vaillant, O., Verdon, R., Verlesch-Langlin, A., Viard, J.-P., Vittecoq, D., Weiss, L., Yéni, P., Zucman, D., Allavena, C., Allegre, T., Amri, I., Autran, B., Bacchus, C., Blanc, C., Bonne, S., Bonne, B., Bouchez, S., Charlier, C., Consigny, H., Duvivier, C., Fourn, E., Guiroy, F., Huleux, T., Katlama, C., Lascoux, C., Leplatois, A., Lyavanc, T., Molina, J.-M., Naqvi, A., Nembot, G., Quertainmont, Y., Raffi, F., Samri, A., Schneider, L., Seang, S., Seksik, B., Shoai-Tehrani, M., Slama, L., Valentin, A., Yazdanpanah, Y., Alloui, C., Amiel, C., André, P., André, E., Anies, G., Barin, F., Bellecave, P., Bettinger, D., Bouvier-Alias, M., Brun-Vézinet, F., Calmy, A., Calvez, V., Caveng, W., Chaillon, A., Chapalay, S., Charpentier, C., Costagliola, D., Cottalorda, J., Delamare, C., Delaugerre, C., Dina, J., Santos, G., Ferre, V., Flandre, P., Fleury, H., Fourati, S., Gaille, C., Giraudeau, G., Guigon, A., Haim-Boukobza, S., Lagier, E., Le Guillou-Guillemette, H., Henquell, C., Izopet, Jacques, Lambert-Niclot, Lambert, Leroux, M., Maillard, A., Malet, I., Marcelin, Marc, Marque-Juillet, S., Masquelier, B., Mirand, A., Morand, P., Montes, B, Mouna, L., Noel, C., Pallier, C., Peytavin, G., Pinson-Recordon, P., Poveda, J., Raymond, S., Reigadas, S., Roques, A., de Rougemont, A., Roussel, C., Schmitt, P., Schneider, V., Schvoerer, E., Signori-Schmuck, A., Soulié, C., Tamalet, C., Tardy, C., Trabaud, A., Vabret, A., Vallet, S., Yerly, S., Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Necker], Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), 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), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Departement d'épidémiologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Labex_Transplantex (Labex_Transplantex), Laboratoire de Virologie [Strasbourg], Laboratoire de microbiologie [CHRU Orléans], Centre Hospitalier Régional d'Orléans (CHRO), 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 Toulouse], CHU Toulouse [Toulouse], Coordination Régionale de la lutte contre l'infection due au VIH (COREVIH), COREVIH, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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 Microbiologie Clinique, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pharmacie, inconnu, Inconnu, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service des maladies infectieuses et tropicales, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, Service des Maladies infectieuses et tropicales [CHU Limoges], Infectious Diseases Department, Université Montpellier 1 (UM1), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Jean Verdier [AP-HP], Laboratoire d'Ecologie Numérique et d'Ecotoxicologie, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Infectious diseases department, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Bell Labs (BELL), Lucent Technologies, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Département d'infectiologie (CHU de Dijon), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), STMicroelectronics, Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), service pharmaceutique Hôpital Edouard Herriot, Hospices Civils de Lyon, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Université de stuttgart, Université de Stuttgart, Hôpital Raymond Poincaré [AP-HP], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier du Pays d'Aix, Nivologie (UR NIGR), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Tourcoing, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de radiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Santé et de la Recherche Médicale (INSERM), UMR CNRS 8179, Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Geneva University Hospital (HUG), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Service de microbiologie [Saint-Louis], PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), 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), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Equipe 15, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), 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), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Service de virologie [CHU Pitié-Salpêtrière], INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Labex_Transplantex ( Labex_Transplantex ), Centre Hospitalier Régional d'Orléans ( CHR ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Coordination Régionale de la lutte contre l'infection due au VIH ( COREVIH ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHR), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie et de santé publique des armées (CESPA), Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, AP-HP Hôpital Raymond Poincaré [Garches], Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Besançon, Université de Franche-Comté (UFC), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service des maladies infectieuses et réanimation médicale [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Male, Microbiology (medical), Efavirenz, Genotype, Genotyping Techniques, Anti-HIV Agents, Mutation, Missense, Human immunodeficiency virus (HIV), Etravirine, Integrase inhibitor, HIV Infections, Drug resistance, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Men who have sex with men, chemistry.chemical_compound, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Drug Resistance, Viral, Disease Transmission, Infectious, Prevalence, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Primary HIV infection, Pharmacology (medical), Homosexuality, Male, ComputingMilieux_MISCELLANEOUS, Pharmacology, virus diseases, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Rilpivirine, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Resistance-associated mutations, medicine.drug
Abstract: Background Our study describes the prevalence of transmitted drug resistance (TDR) among 1318 French patients diagnosed at the time of primary HIV-1 infection (PHI) in 2007–12. Methods HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 WHO list of mutations and the French ANRS algorithm. A genotypic susceptibility score was estimated for each first-line recommended ART combination. Results Patients were mainly MSM (72.6%). Non-B variants were identified in 33.7% of patients. The proportion of TDR was estimated as 11.7% (95% CI 10.0–13.5). The prevalences of PI-, NRTI-, first-generation NNRTI and etravirine/rilpivirine-associated RAMs were 2.5%, 5.2%, 3.9% and 3.2%, respectively. Single, dual and triple class resistance was found in 9.6%, 1.0% and 1.1% of cases, respectively. Additionally, 5/331 strains isolated in 2010–12 had integrase inhibitor (II)-related RAMs (isolated E157Q mutation in all cases). TDR was more common among MSM than in other groups (12.9% versus 8.6%, P = 0.034), and in case of B versus non-B subtype infections (13.6% versus 7.9%, P = 0.002). The proportions of fully active combinations were ≥99.2%, ≥97.3% and ≥95.3% in cases of PI-, II- and NNRTI-based regimens, respectively. In 2010–12, the proportion of fully active efavirenz-based ART was lower in cases of subtype B versus non-B infection (P = 0.021). Conclusions Compared with our previous studies, the proportion of NRTI- and first-generation NNRTI-related TDR has continued to decline in French seroconverters. However, subtype B-infected MSM could drive the spread of resistant HIV strains. Finally, we suggest preferring PI- or II- to NNRTI-based combinations to treat PHI patients.
Published: 2015
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41. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author: Soulié, Cathia, Descamps, Diane, Ronique Schneider, Vé, Trabaud, Mary-Anne, Morand-Joubert, Laurence, Delaugerre, Constance, Montes, Brigitte, Barin, Francis, Ferré, Virginie, Maillard, Anne, Vallet, Sophie, Roussel, Catherine, Assoumou, Lambert, Calvez, Vincent, Flandre, Philippe, Ve, Anne-Geneviè, Jeulin, H., Guigon, A., Lagier, E., Le Guillou, H., Alloui, C., Bettinger, D., Pallier, C., Fleury, H., Reigadas, S., Bellecave, P., Recordon-Pinson, P., Payan, C., Vabret, A., Henquell, C., Mirand, A., Bouvier-Alias, M., de Rougemont, Alexis, dos Santos, G., Morand, P., Signori-Schmuck, A., Bocket, L., Rogez, S., Andre, P., Tardy, J., Tamalet, C., Delamare, C., Schvoerer, E., André-Garnier, E., Cottalorda, J., Guinard, J., Guiguon, A., Brun-Vezinet, F., Charpentier, C., Visseaux, B., Peytavin, G., Krivine, A., Si-Mohamed, A., Avettand-Fenoel, V., Marcelin, A.-G., Lambert-Niclot, S., Wirden, M., Chaix, M., Amiel, C., Schneider, V., Giraudeau, G., Brodard, V., Plantier, J., Chaplain, C., Bourlet, T., Fafi-Kremer, S., Stoll-Keller, F., Schmitt, M., Barth, H., Yerly, S., Poggi, C., Izopet, Jacques, Raymond, S., Chaillon, A., Marque-Juillet, S., Roque-Afonso, A., Haim-Boukobza, S., Grude, Maxime, Costagliola, D., Allegre, T., Schmit, J., Chennebault, J., Bouchaud, O., Magy-Bertrand, N., Delfraissy, J., Dupon, M., Morlat, P., Neau, D., Ansart, S., Jaffuel, S., Verdon, R., Jacomet, C., Levy, Y., Dominguez, S., Chavanet, P., Piroth, L., Cabié, A., Leclercq, P., Ajana, F., Cheret, A., Weinbreck, P., Cotte, L., Poizot-Martin, I., Ravaud, I., Christian, B., Truchetet, F., Grandidier, M., Reynes, J., May, T., Goehringer, F., Raffi, F., Dellamonica, P., Prazuck, T., Hocqueloux, L., Yeni, P., Landman, R., Launay, O., Weiss, L., Viard, J., Katlama, C., Simon, A., Girard, Pascal, Meynard, J., Molina, J., Pialoux, G., Hoen, B., Goeger-Sow, M., Lamaury, I., Beaucaire, G., Jaussaud, R., Rouger, C., Michelet, C., Borsa-Lebas, F., Caron, F., Khuong, M., Lucht, F., Rey, D., Calmy, A., Marchou, B., Gras, G., Greder-Belan, A., Vittecoq, D., Teicher, E., Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de bactériologie-virologie, 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), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre national de référence du VIH INSERM U966, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Faculté de médecine et pharmacie, CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de sérologie-virologie (CHU de Dijon), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Laboratoire d'Informatique de Nantes Atlantique (LINA), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'électronique, optoélectronique et microsystèmes (LEOM), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôtel-Dieu de Nantes, Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), 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), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Strasbourg], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Environment and Sustainable Development Programme, European Commission - DG Research and Innovation, Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Magnétisme et Diffusion Neutronique (MDN), Modélisation et Exploration des Matériaux (MEM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier du Pays d'Aix, CHU Bordeaux [Bordeaux], Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Service de médecine interne 2 et maladies infectieuses, Unité de Maladies Infectieuses et Tropicales [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Département d'infectiologie (CHU de Dijon), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Bell Labs (BELL), Lucent Technologies, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service des maladies infectieuses et tropicales [CHU Nantes], CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut d’Electronique et des Systèmes (IES), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), CHU Saint-Etienne, CHU Strasbourg, Geneva University Hospital (HUG), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Besançon, Université de Franche-Comté (UFC), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Orléans, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pitié-Salpêtrière [APHP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), University of Applied Sciences Kaiserslautern, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, REseau national d'Investigation clinique en VACcinologie (REIVAC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de Gestion des Essais de Produits de Santé (CeNGEPS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Estación Experimental de Pastos y Forrajes 'Indio Hatuey', Société Ragt 2N, Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-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), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Mines Nantes (Mines Nantes)-Université de Nantes (UN), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Laboratoire de virologie, Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon, Université Grenoble Alpes (UGA), Station de recherches sur la vache laitière, Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hôpital Arnaud de Villeneuve, T2, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), and de ROUGEMONT, Alexis
Subjects: Male, Drug Resistance, HIV Infections, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Genotype, Pharmacology (medical), 030212 general & internal medicine, Viral, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ddc:616, 0303 health sciences, Mutation, medicine.diagnostic_test, Proteolytic enzymes, virus diseases, Pharmacology and Pharmaceutical Sciences, Viral Load, Middle Aged, 3. Good health, ANRS Resistance AC11 Group, Infectious Diseases, Medical Microbiology, [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, ARV, Female, Infection, Viral load, Microbiology (medical), Adult, Anti-HIV Agents, Antiretroviral Therapy, CSF, Microbial Sensitivity Tests, Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, Virus, resistance, 03 medical and health sciences, Clinical Research, Drug Resistance, Viral, medicine, Genetics, Humans, Highly Active, Gene, Pharmacology, 030306 microbiology, Lumbar puncture, Neurosciences, HIV, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, Immunology, HIV-1, Antimicrobial Resistance, Nervous System Diseases
Abstract: International audience; Objectives: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were .50 copies/mL in both compartments and bulk genotypic tests were realized. Results: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P ¼ 0.0455) and T215Y (P ¼0.0455). Conclusions: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.
Published: 2015
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42. Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

Author: Larrat, Sylvie, Vallet, Sophie, David-Tchouda, Sandra, Caporossi, Alban, Margier, Jennifer, Ramière, Christophe, Scholtès, Caroline, Haïm-Boukobza, Stéphanie, Roque-Afonso, Anne-Marie, Besse, Bernard, André-Garnier, Elisabeth, Mohamed, Sofiane, Halfon, Philippe, Pivert, Adeline, Leguillou-Guillemette, Hélène, Abravanel, Florence, Guivarch, Matthieu, Mackiewicz, Vincent, Lada, Olivier, Mourez, Thomas, Plantier, Jean-Christophe, Baazia, Yazid, Alain, Sophie, Hantz, Sébastien, Thibault, Vincent, Gaudy-Graffin, Catherine, Bouvet, Dorine, Mirand, Audrey, Henquell, Cécile, Gozlan, Joël, Lagathu, Gisèle, Pronier, Charlotte, Velay, Aurélie, SCHVOERER, Evelyne, Trimoulet, Pascale, Fleury, Hervé, Bouvier-Alias, Magali, BROCHOT, Etienne, Duverlie, Gilles, Maylin, Sarah, Gouriou, Stéphanie, Pawlotsky, Jean-Michel, Morand, Patrice, Plantier, Christophe, Tang, Y.-W., Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Hôtel-Dieu de Nantes, Alphabio Laboratory, Hôpital Européen [Fondation Ambroise Paré - Marseille], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150) (CPTP), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, Centre de recherche sur l'Inflammation (CRI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Université de Limoges (UNILIM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, CHU Pontchaillou [Rennes], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et pathogénie des infections à entérovirus (EPIE), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [APHP], Virology Laboratory, General Hospital Papageorgiou, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de Virologie clinique et fondamentale EA 4294, CHU Amiens-Picardie, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie moléculaire et structurale, CHU Grenoble, Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité d'évaluation clinique et médico-économique [CHU Grenoble] (Département de la recherche clinique et de l'innovation), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Virologie [Villejuif], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Laboratoire de Virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ALPHABIO - Laboratoire de biologie médicale, Laboratoire de virologie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Virologie [CHU Purpan, Toulouse], Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre national de référence du VIH INSERM U966, Université de Tours (UT), CHU Clermont-Ferrand, 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 [Rennes] = Virology [Rennes], Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de bactériologie - hygiène [CHU Amiens], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Unit for Virus Host-Cell Interactions [Grenoble] ( UVHCI ), Université Joseph Fourier - Grenoble 1 ( UJF ) -European Molecular Biology Laboratory [Grenoble] ( EMBL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne ( LUBEM ), Université de Brest ( UBO ), ThEMAS, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Institut d'Enseignement Supérieur et de Recherche en Alimentation, Santé Animale, Sciences Agronomiques et de l'Environnement ( VetAgro Sup ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Institut d'Enseignement Supérieur et de Recherche en Alimentation, Santé Animale, Sciences Agronomiques et de l'Environnement ( VetAgro Sup ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -CHU Grenoble, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-CHU Grenoble, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Internal Medicine and Infectious Diseases Department, European Hospital and Alphabio Laboratory, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Hôpital Bichat - Claude Bernard, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Biomédicale des Armées ( IRBA ), CHU Avicenne, Service de virologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -CHU Pitié-Salpêtrière [APHP], Morphogénèse et antigénicité du VIH et du virus des Hépatites ( MAVIVH ), Université de Tours-Centre Hospitalier Régional Universitaire de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Calcul de l'IN2P3 ( CC-IN2P3 ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Strasbourg, Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Microbiologie cellulaire et moléculaire et pathogénicité ( MCMP ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Faculté de Médecine, CHU Henri Mondor, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-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), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, SCHVOERER, Evelyne, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Université de Tours
Subjects: Male, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Hepacivirus, MESH: Treatment Outcome, MESH: Inhibitory Concentration 50, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Aged, education.field_of_study, MESH: Drug Resistance, Viral, MESH: Middle Aged, MESH: Protease Inhibitors, Hepatitis C, Middle Aged, 3. Good health, MESH: Hepatitis C, Chronic, Treatment Outcome, MESH: Oligopeptides, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, MESH: Interferon-alpha, Viral load, Oligopeptides, medicine.drug, Microbiology (medical), MESH: Antiviral Agents, Adult, medicine.medical_specialty, Proline, Hepatitis C virus, Population, Mutation, Missense, Antiviral Agents, Inhibitory Concentration 50, MESH: Ribavirin, Internal medicine, Boceprevir, Virology, Drug Resistance, Viral, Ribavirin, medicine, Humans, Protease Inhibitors, education, Aged, Retrospective Studies, MESH: Mutation, Missense, MESH: Humans, MESH: Proline, business.industry, Interferon-alpha, MESH: Adult, MESH: Retrospective Studies, Hepatitis C, Chronic, medicine.disease, MESH: Male, chemistry, Immunology, MESH: Viral Nonstructural Proteins, business, MESH: Female, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of 3-fold shift in 50% inhibitory concentration (IC 50 ) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) ( P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.
Published: 2015
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43. Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France

Author: Thierry May, François Goehringer, L. Boyer, Pascale Perrier, Aurélie Velay, Evelyne Schvoerer, Christian Rabaud, Nelly Agrinier, Anne Kennel, M. Foissac, Hélène Jeulin, Sandrine Henard, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), and Laboratoire d'histocompatibilité [CHU Nancy]
Subjects: Microbiology (medical), Male, medicine.medical_specialty, Anti-HIV Agents, Non-nucleoside reverse transcriptase inhibitors, HIV Infections, Disease cluster, Virus, Men who have sex with men, chemistry.chemical_compound, Epidemiology, Drug Resistance, Viral, Nitriles, Medicine, Humans, Pharmacology (medical), Retrospective Studies, Pharmacology, business.industry, Rilpivirine, Retrospective cohort study, Virology, 3. Good health, Discovery and development of non-nucleoside reverse-transcriptase inhibitors, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Cross-Sectional Studies, Pyrimidines, chemistry, Cohort, NNRTIs, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Resistance-associated mutations, France, business
Abstract: International audience; To assess the prevalence of resistance to rilpivirine and mutations at position 138 in reverse transcriptase and to identify associated epidemiological and biological characteristics.This retrospective study included 238 patients with available HIV-1 nucleotide sequences analysed at the Laboratory of Virology at the University Hospital of Nancy between January 2011 and June 2013. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was evaluated according to the ANRS algorithm (version 23) and correlated with clinico-epidemiological and therapeutic data. The virus strains were analysed by evaluating the distance and distribution of the phylogenetic tree (MEGAv5).Among previously treated patients (111/238, 46.6%), 68/111 (61.3%) had received NNRTIs; all were rilpivirine-naive. The prevalence of rilpivirine resistance in the whole cohort was 12.6% (30/238), and was 10.2% (13/127) and 15.3% (17/111) in naive and pre-treated patients, respectively. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (PaEuroS < aEuroS0.0001). The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (PaEuroS=aEuroS0.0614). Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster.In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. Taken together, our results emphasize the need to investigate the prevalence of rilpivirine resistance-associated mutations in the coming years both in France and abroad.
Published: 2014
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44. Clinical impact of hepatitis B and C virus envelope glycoproteins

Author: Aurélie Velay, John M. Murray, Hélène Jeulin, Evelyne Schvoerer, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), The Kirby Institute, University of New South Wales [Sydney] (UNSW), School of Mathematics and statistics [Sydney], and The University of Sydney
Subjects: Hepatitis B virus, Genotype, medicine.drug_class, Hepacivirus, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, Hepatitis B virus PRE beta, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Viral Envelope Proteins, Viral envelope, Viral envelope glycoproteins, Viral entry, Drug Resistance, Viral, medicine, Animals, Humans, Hepatitis B Vaccines, 030304 developmental biology, 0303 health sciences, biology, Clinical outcome, Gastroenterology, virus diseases, Minireviews, General Medicine, Hepatitis C, Chronic, Hepatitis B, Prognosis, medicine.disease, biology.organism_classification, Virology, Hepatitis C, digestive system diseases, 3. Good health, Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Antiviral drug
Abstract: International audience; Chronic infection by either hepatitis B virus (HBV) or hepatitis C virus (HCV) share epidemiological characteristics with risks for development of severe complications such as liver cirrhosis and hepatocellular carcinoma. HBV and HCV also share a high genetic variability. Among highly variable regions, viral genes encoding surface proteins (hepatitis B surface antigen, E1/E2 HCV glycoproteins) play key roles in the stimulation of the host-related immune response and viral entry into hepatocytes. Specific segments of HBV envelope proteins (preS1, "a" determinant) are crucial in the entry process into permissive cells. HCV entry is a complex multistep process involving multiple cell cofactors (glycosaminoglycans, low density lipoprotein receptor, SR-B1, CD81, claudin-1, occludin, EGFR, EphA2) in the interaction with HCV E1/E2 envelope glycoproteins. In vitro both viruses can be controlled by antibody-mediated neutralization targeting viral envelope, also essential in preventing HBV infection in vivo as observed through successful vaccination using HBs antigen. But preventive vaccination and/or therapeutic pressure can influence HBV and HCV variability. For HBV, the patterns of antiviral drug resistance in chronic hepatitis are complex and the original pol/S gene overlap has to be taken into account. Treatment-induced HBV mutations in pol could indeed generate S mutants with subsequent modified antigenicity or increased cancer induction. Variability of HBV and HCV envelope proteins combining high exposure to selective pressures and crucial functional roles require investigation in the context of diagnostic, vaccination and treatment tools. In this editorial a synthesis is performed of HBV and HCV envelope properties at the entry step and as antigenic proteins, and the subsequent clinical impact.
Published: 2013
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45. Genotype 1 hepatitis C virus envelope features that determine antiviral response assessed through optimal covariance networks

Author: Françoise Stoll-Keller, Michel Doffoel, Isabel Fofana, Evelyne Schvoerer, Thomas F. Baumert, Aurélie Velay, François Habersetzer, Jean-Pierre Gut, Mirjam B. Zeisel, Rémy Moenne-Loccoz, John M. Murray, SCHVOERER, Evelyne, School of Mathematics and Statistics, University of New South Wales [Sydney] (UNSW), The Kirby Institute for Infection and Immunity in Society (UNSW), Pôle Hépato-digestif [Strasbourg] (HUS - Nouvel Hôpital Civil), Les Hôpitaux Universitaires de Strasbourg (HUS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA), Laboratoire de Virologie [Strasbourg], and This work was supported by the European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Supe´rieur-FEDER-Hepato-Regio-Net 2009), the chair of excellence program of the Agence Nationale de la Recherche France (ANR-05-CEXC-008), ANRS (2011/132, 2011/154, 2012/239&319, 2012/318), DGOS Inserm A12027MS, the University of Strasbourg and Laboratoire d’excellence LabEx HEPSYS (ANR-10-LAB-28). E. Schvoerer thanks the Fondation Transplantation (France), Region Alsace (France), Region Lorraine (France), Abbott Molecular (France) and Roche (France) for unrestricted financial support.
Subjects: Gastroenterology and hepatology, Hepacivirus, lcsh:Medicine, medicine.disease_cause, Hepatitis, 0302 clinical medicine, Viral Envelope Proteins, Genotype, lcsh:Science, Mathematical Computing, Phylogeny, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Mutation, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Systems Biology, Applied Mathematics, Viral Envelope Gene, virus diseases, Hepatitis C, 3. Good health, Infectious hepatitis, Treatment Outcome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Infectious diseases, 030211 gastroenterology & hepatology, Research Article, Hepatitis C virus, Alpha interferon, Viral diseases, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Antiviral Agents, Models, Biological, 03 medical and health sciences, Viral entry, Ribavirin, medicine, Humans, Biology, Liver diseases, 030304 developmental biology, Models, Statistical, lcsh:R, Interferon-alpha, Computational Biology, biology.organism_classification, Virology, Hypervariable region, Multivariate Analysis, lcsh:Q, Mathematics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The poor response to the combined antiviral therapy of pegylated alfa-interferon and ribavarin for hepatitis C virus (HCV) infection may be linked to mutations in the viral envelope gene E1E2 (env), which can result in escape from the immune response and higher efficacy of viral entry. Mutations that result in failure of therapy most likely require compensatory mutations to achieve sufficient change in envelope structure and function. Compensatory mutations were investigated by determining positions in the E1E2 gene where amino acids (aa) covaried across groups of individuals. We assessed networks of covarying positions in E1E2 sequences that differentiated sustained virological response (SVR) from non-response (NR) in 43 genotype 1a (17 SVR), and 49 genotype 1b (25 SVR) chronically HCV-infected individuals. Binary integer programming over covariance networks was used to extract aa combinations that differed between response groups. Genotype 1a E1E2 sequences exhibited higher degrees of covariance and clustered into 3 main groups while 1b sequences exhibited no clustering. Between 5 and 9 aa pairs were required to separate SVR from NR in each genotype. aa in hypervariable region 1 were 6 times more likely than chance to occur in the optimal networks. The pair 531-626 (EI) appeared frequently in the optimal networks and was present in 6 of 9 NR in one of the 1a clusters. The most frequent pairs representing SVR were 431-481 (EE), 500-522 (QA) in 1a, and 407-434 (AQ) in 1b. Optimal networks based on covarying aa pairs in HCV envelope can indicate features that are associated with failure or success to antiviral therapy.
Published: 2013
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46. Analyses of the effects of collection and processing time on the results of serology testing of cadaveric cornea donors

Author: Hélène Jeulin, Danièle Bensoussan, Nelly Agrinier, Véronique Venard, Véronique Decot, Unité de Thérapie Cellulaire et Tissulaire [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), and Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R)
Subjects: Male, Microbiology (medical), medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Centrifugation, 030204 cardiovascular system & hematology, Donor Selection, Specimen Handling, Serology, Cornea, 03 medical and health sciences, 0302 clinical medicine, Decantation, Cadaver, medicine, Humans, Serologic Tests, Sampling (medicine), ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, General Medicine, Middle Aged, Cornea donors, Tissue Donors, 3. Good health, Surgery, Time of death, Death, Infectious Diseases, medicine.anatomical_structure, Virus Diseases, Female, 030211 gastroenterology & hepatology, Cadaveric spasm, business
Abstract: Serologic testing results are one of the major reasons for discarding donor corneas. This study assessed the prevalence of serologic markers and the times of preanalytic steps. The prevalence of serologic markers in 705 cornea donors of the Lorraine region was studied. One hundred forty-one (20%) corneas were discarded on the basis of serologic testing. In a subsample of 180 consecutive cornea donors, data concerning the time of death, sampling, and serology testing were collected. When the time between death and sampling did not exceed 8 h (n = 122), immediate decantation (separation of serum from clot) led to less discarding of corneas than delayed decantation (2/46 [4.3%] discarded in the group with immediate decantation versus 13/76 [17.1%] discarded in the group with delayed decantation [P = 0.038]). For blood samples collected within 8 h of death, the rate of reactive results is significantly lower if samples are immediately decanted.
Published: 2010
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47. Contribution of human herpesvirus 6 (HHV-6) viral load in whole blood and serum to investigate integrated HHV-6 transmission after haematopoietic stem cell transplantation

Author: Henri Agut, Alexandra Salmon, Agnès Gautheret-Dejean, Véronique Venard, Pierre Bordigoni, Bernard Fortier, Hélène Jeulin, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Infantile II [CHRU Nancy], Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Adolescent, viruses, Herpesvirus 6, Human, Virus Integration, [SDV]Life Sciences [q-bio], Roseolovirus Infections, Virus Replication, Antiviral Agents, Polymerase Chain Reaction, Virus, 03 medical and health sciences, Blood serum, Virology, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Whole blood, 0303 health sciences, Analysis of Variance, biology, 030306 microbiology, Hematopoietic Stem Cell Transplantation, virus diseases, Viral Load, biology.organism_classification, Tissue Donors, 3. Good health, Transplantation, Haematopoiesis, Infectious Diseases, Real-time polymerase chain reaction, Immunology, DNA, Viral, Regression Analysis, Human herpesvirus 6, Female, Viral load
Abstract: Background Human herpesvirus 6 (HHV-6) is susceptible to latency and recurrence. A less-frequent form of HHV-6 persistence is the integration of viral DNA into host chromosomes. Objectives To investigate HHV-6 viral load after haematopoietic stem cell transplantation (HSCT) in whole blood (WB) and serum with regard to integrated HHV-6 transmission diagnosis. Study design HHV-6 DNA quantitation in serum and WB was performed using quantitative polymerase chain reaction for the follow-up of a 16-year-old girl after HSCT. In whole blood, results were expressed as HHV-6 genomic equivalent copies (gec) per milliliter of WB or per million cells. Results HHV-6 viral load (undetectable before HSCT) increased up to 3.05 × 107 gec/106 cells. HHV-6 viral load in the donor sample (3.44 × 106 gec/106 cells) was in favor of viral transmission through HSCT. The correlation between viral load in WB and serum was significant (p = 0.0005). Viral load results expressed as gec/106 cells in WB was more reliable than results expressed as gec/ml of whole blood. Conclusion These findings indicate that HHV-6 may be transmitted during HSCT as integrated virus contained in the graft. This reiterates that in the setting of HSCT, HHV-6 viral load must be correctly interpreted. Using HHV-6 viral load expressed as gec/106 cells may be more suitable for the follow-up of patients with integrated HHV-6.
Published: 2009
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48. Effective ribavirin concentration in mice brain using cyclodextrin as a drug carrier: evaluation in a measles encephalitis model

Author: D. Carapito, Véronique Venard, F. Kedzierewicz, Chantal Finance, H. Jeulin, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, Time Factors, [SDV]Life Sciences [q-bio], viruses, medicine.medical_treatment, Intraperitoneal injection, Measles virus, 03 medical and health sciences, chemistry.chemical_compound, Mice, Morbillivirus, Pharmacokinetics, In vivo, Virology, Ribavirin, medicine, Animals, Encephalitis, Viral, ComputingMilieux_MISCELLANEOUS, Chromatography, High Pressure Liquid, 030304 developmental biology, Pharmacology, Brain Chemistry, 0303 health sciences, Cyclodextrins, Drug Carriers, biology, 030306 microbiology, business.industry, Viral encephalitis, virus diseases, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, digestive system diseases, 3. Good health, chemistry, Female, business, Encephalitis, Measles
Abstract: Ribavirin (RBV) is a water-soluble synthetic nucleoside with broad spectrum antiviral properties, but it is ineffective against major viral encephalitis because of a failure to cross the blood–brain barrier (BBB). The antiviral activity of the complex ribavirin/alpha-cyclodextrin was previously demonstrated to be stronger than free ribavirin, in an in vivo model of measles virus (MV) encephalitis in mice. The role of cyclodextrin (CD) on ribavirin uptake into the brain needs to be defined. Ribavirin specific extraction from brain tissue was developed, based on a solid phase extraction. It was quantified by high performance liquid chromatography at different time points after intraperitoneal injection of single or multiple doses of free ribavirin or of the complex ribavirin/alpha-cyclodextrin. Whatever the tested dose (40 or 100 mg/kg), the amount of ribavirin in the brain was significantly higher (p < 0.001) when the drug was injected as a complex with alpha-cyclodextrin, in healthy or measles virus-infected mice.
Published: 2008
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49. In vivo antiviral activity of ribavirin/alpha-cyclodextrin complex: evaluation on experimental measles virus encephalitis in mice

Author: F. Kedzierewicz, Nicolas Grancher, Chantal Finance, A. Le Faou, H. Jeulin, Véronique Venard, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, alpha-Cyclodextrins, DNA, Complementary, Paramyxoviridae, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Intraperitoneal injection, Pharmaceutical Science, Antiviral Agents, Virus, Measles virus, 03 medical and health sciences, chemistry.chemical_compound, Mice, Morbillivirus, Ribavirin, medicine, Animals, Encephalitis, Viral, Mononegavirales, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Reference Standards, Viral Load, biology.organism_classification, Virology, Survival Analysis, 3. Good health, chemistry, DNA, Viral, Mice, Inbred CBA, RNA, Female, Viral load, Measles
Abstract: Intracranial injection of the rodent adapted CAM/RB strain of measles virus (MV) induces encephalitis in CBA/ca mice. It has already been shown that cyclodextrins can be used as carriers to increase the antiviral activity of ribavirin (RBV) against MV in cellular model. In this study, the antiviral activity of a RBV/alpha-cyclodextrin complex has been evaluated in vivo using the above model. CBA/ca mice were treated by intraperitoneal injection of free ribavirin (40 mg/kg) or a RBV/alpha-cyclodextrin complex (molar ratio 1:3). After 21 days, intracerebral injection of CAM/RB resulted in 100% mortality in the mock group. In contrast, mortality rates of 80% and 40%, respectively, were observed in RBV and RBV/alpha-CD-treated mice (p0.05 and p=0.06 for distilled water and RBV, respectively). The viral load of MV in the mouse brain was monitored daily by real-time PCR until day 6 after infection, to compare virus production in treated and non-treated mice. This data shows that RBV complexation with alpha-cyclodextrin can increase the antiviral activity of ribavirin in a measles virus encephalitis model in mice.
Published: 2007
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