Author: "Anne Signori-Schmuck" - Searchworks@Jio Institute Digital Library Search Results

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1. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma.

Author: Hélène Le Guillou-Guillemette, Adeline Pivert, Elise Bouthry, Cécile Henquell, Odile Petsaris, Alexandra Ducancelle, Pascal Veillon, Sophie Vallet, Sophie Alain, Vincent Thibault, Florence Abravanel, Arielle A Rosenberg, Elisabeth André-Garnier, Jean-Baptiste Bour, Yazid Baazia, Pascale Trimoulet, Patrice André, Catherine Gaudy-Graffin, Dominique Bettinger, Sylvie Larrat, Anne Signori-Schmuck, Hénia Saoudin, Bruno Pozzetto, Gisèle Lagathu, Sophie Minjolle-Cha, Françoise Stoll-Keller, Jean-Michel Pawlotsky, Jacques Izopet, Christopher Payan, Françoise Lunel-Fabiani, and Christophe Lemaire
Subjects: Medicine, Science
Abstract: BACKGROUND:The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. METHODS:Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. RESULTS:Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. CONCLUSIONS:These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.
Published: 2017
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2. Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey

Author: Anne-Genevieve, Marcelin, Charlotte, Charpentier, Pantxika, Bellecave, Basma, Abdi, Marie-Laure, Chaix, Virginie, Ferre, Stephanie, Raymond, Djeneba, Fofana, Laurence, Bocket, Audrey, Mirand, Helene, Le Guillou-Guillemette, Brigitte, Montes, Corinne, Amiel, Coralie, Pallier, Samira, Fafi-Kremer, Anne, De Monte, Elodie, Alessandri-Gradt, Caroline, Scholtes, Anne, Maillard, Helene, Jeulin, Magali, Bouvier-Alias, Catherine, Roussel, Georges, Dos Santos, Anne, Signori-Schmuck, Julia, Dina, Sophie, Vallet, Karl, Stefic, Cathia, Soulié, Vincent, Calvez, Diane, Descamps, Philippe, Flandre, S, Marque Juillet, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, CHU Strasbourg, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), 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), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Amiens-Picardie, CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Caen Normandie (UNICAEN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de virologie et unité de surveillance biologique [Bordeaux], Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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, Oncology, genotype, Integrase inhibitor, hiv, HIV Infections, gerstmann-straussler-scheinker, HIV Integrase, viral load result, chemistry.chemical_compound, 0302 clinical medicine, Genotype, Pharmacology (medical), 030212 general & internal medicine, Univariate analysis, biology, 3. Good health, Integrase, univariate analysis, integrase inhibitors, Infectious Diseases, Tolerability, Dolutegravir, Heterocyclic Compounds, 3-Ring, medicine.drug, Microbiology (medical), medicine.medical_specialty, Pyridones, 030106 microbiology, 03 medical and health sciences, Internal medicine, Raltegravir Potassium, Drug Resistance, Viral, medicine, Humans, HIV Integrase Inhibitors, plasma, Pharmacology, disease, business.industry, genetics raltegravir dolutegravir, Raltegravir, Regimen, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Mutation, biology.protein, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, hiv-1 integrase, business
Abstract: Background Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. Materials and methods A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. Results Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0–0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. Conclusions This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.
Published: 2021

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

Author: Ali Si-Mohammed, Jean-Dominique Poveda, Theresa Rabenja, B Visseaux, Karl Stefic, Fabienne De Oliveira, Anne Signori-Schmuck, Audrey Mirand, Magali Bouvier-Alias, Stéphanie Raymond, Vincent Calvez, Pantxika Bellecave, Coralie Pallier, Anne-Geneviève Marcelin, Véronique Schneider, Sidonie Lambert-Niclot, Chakib Alloui, Marie-Laure Chaix, Jean-Christophe Plantier, Diane Descamps, Elisabeth André-Garnier, Brice Malve, Marc Wirden, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire CERBA [Saint Ouen l'Aumône], Grand Hôpital de l'Est Francilien (GHEF), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Mzembaba, Sandy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Caen Normandie (UNICAEN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP]
Subjects: Male, 0301 basic medicine, Epidemiology, HIV Infections, Disease Outbreaks, Men who have sex with men, MESH: HIV Infections / epidemiology, Sexual and Gender Minorities, 0302 clinical medicine, Pandemic, Cluster Analysis, 030212 general & internal medicine, MESH: Phylogeny, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: HIV cluster, HIV CRF94, phylogenetic analysis, HIV Outbreak, HIV Prevention, Recombination, Genetic, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, education.field_of_study, MESH: France / epidemiology, Surveillance, Virulence, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), Viral Load, MESH: Drug Resistance, Viral / genetics, 3. Good health, MESH: HIV-1 / genetics, Phylogeography, MESH: Online Social Networking, Online Social Networking, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, MESH: Disease Outbreaks / prevention & control, Adult, medicine.medical_specialty, Population, MESH: HIV-1 / classification, MESH: HIV-1 / pathogenicity, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Disease cluster, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, MESH: HIV Infections / transmission, 03 medical and health sciences, Virology, Environmental health, Drug Resistance, Viral, medicine, Humans, MESH: DNA, Viral / genetics, MESH: HIV Infections / virology, Viremia, MESH: HIV Infections / prevention & control, education, Genotyping, Whole Genome Sequencing, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Cluster Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, HIV cluster, 030104 developmental biology, DNA, Viral, HIV-1, Observational study, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Sequence Alignment
Abstract: Background Ending the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages. Aim This observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF’s novelty as well as measures to control its spread are presented. Methods Phylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases’ clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire. Results The transmission cluster comprised 49 cases, mostly diagnosed in 2016–2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log10 copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken. Conclusion We advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.
Published: 2019

4. 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

5. 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

6. Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen

Author: Alexandre Storto, Diane Descamps, Anne Maillard, Audrey Mirand, Corinne Amiel, Charlotte Charpentier, Vincent Calvez, Thuy Van Nguyen, Laurence Bocket, Coralie Pallier, Audrey Rodallec, Elisabeth André-Garnier, Marie Leoz, Laurence Morand-Joubert, Isabelle Malet, Stéphanie Raymond, Véronique Schneider, Catherine Roussel, Camille Tumiotto, Constance Delaugerre, Anne-Geneviève Marcelin, Julia Dina, Jean-Christophe Plantier, Brigitte Montes, Anne Signori-Schmuck, 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), Université Paris Diderot - Paris 7 (UPD7), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 [Toulouse], CHU Toulouse [Toulouse], 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), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Tenon [APHP], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-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), 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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Microbiology (medical), Genotype, 030106 microbiology, Mutation, Missense, Integrase inhibitor, HIV Infections, HIV Integrase, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, 03 medical and health sciences, chemistry.chemical_compound, Gene Frequency, medicine, Prevalence, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Pharmacology, biology, Elvitegravir, business.industry, Viral Load, Raltegravir, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Integrase, Regimen, Infectious Diseases, Treatment Outcome, chemistry, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, France, business, Viral load, medicine.drug
Abstract: International audience; ObjectivesTo assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.MethodsThis was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.ResultsPrevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL
Published: 2018

7. Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant

Author: Samira Fafi-Kremer, Laurence Morand-Joubert, Audrey Mirand, Vincent Calvez, Cathia Soulié, Mary-Anne Trabaud, A G Marcelin, Jacqueline Cottalorda, Anne Signori-Schmuck, S. Berger, Julia Dina, Coralie Pallier, Véronique Avettand-Fenoel, Brigitte Montes, Pantxika Bellecave, Karen Zafilaza, Charlotte Charpentier, L. Le Guen, Sabine Yerly, Catherine Roussel, Corinne Amiel, Sophie Sayon, 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), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Virologie [Strasbourg], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), UR 0420 - Station de pathologie végétale, Laboratoire de pathologie forestière, Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), 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), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain Recherche (SGR), SAINT-GOBAIN, CHU Pitié-Salpêtrière [APHP], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbiologie Fondamentale et Pathogénicité (MFP), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Saint-Gobain, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Genotype, Genotyping Techniques, viruses, Concordance, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, ddc:616.07, HIV Envelope Protein gp120, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Virology, HIV tropism, medicine, Humans, False Positive Reactions, 030212 general & internal medicine, Tropism, ComputingMilieux_MISCELLANEOUS, virus diseases, Viral Load, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, CD4 Lymphocyte Count, 3. Good health, Viral Tropism, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Recombinant DNA, RNA, Viral, France, False positive rate, Viral load, Algorithm, Algorithms, Switzerland, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.
Published: 2018

8. Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients

Author: Olivier François, Katia Fusillier, Michael G. B. Blum, Jean-Pierre Zarski, Sylvie Larrat, Pauline Tremeaux, Patrice Morand, Réjane Beugnot, Alice Marlu, Jean-Baptiste Claude, Agnès Plages, Om Kulkarni, Anne Signori-Schmuck, Julien Lupo, Hervé Duborjal, Vincent Leroy, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), 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)-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), Genostar, GENOME Express (GENOME Express), GENOME Express, Earth and Environmental, AMEC, Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon, Pôle Digidune, Pôle DigiDune, Unité de Biophysique, CRSSA, Département d'hépato-gastroentérologie, Université Grenoble Alpes (UGA)-CHU Grenoble, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Grenoble-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-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-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Microbiology (medical), NS3, medicine.medical_specialty, Entropy, medicine.medical_treatment, Mutation, Missense, Salvage therapy, Viral quasispecies, Viral Nonstructural Proteins, Biology, Antiviral Agents, Peripheral blood mononuclear cell, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Drug Resistance, Viral, Genotype, medicine, Humans, Protease Inhibitors, Aged, 030304 developmental biology, Aged, 80 and over, Salvage Therapy, 0303 health sciences, Protease, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Genetic Variation, High-Throughput Nucleotide Sequencing, virus diseases, Odds ratio, Hepatitis C, Chronic, Middle Aged, Prognosis, digestive system diseases, Confidence interval, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], HCV, Immunology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology
Abstract: Despite the gain in sustained virological responses (SVR) provided by protease inhibitors (PIs), failures still occur. The aim of this study was to determine if a baseline analysis of the NS3 region using ultradeep pyrosequencing (UDPS) can help to predict an SVR. Serum samples from 40 patients with previously nonresponding genotype 1 chronic hepatitis C who were retreated with triple therapy, including a PI, were analyzed. Baseline UDPS of the NS3 gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Mutations conferring resistance to PIs were sought. The overall diversity of the quasispecies was evaluated by calculating the Shannon entropy (SE). Resistance mutations were found in plasma and PBMC but were not discriminating enough to predict an SVR. NS3 quasispecies heterogeneity was significantly lower at baseline in patients achieving an SVR than in those not achieving an SVR (SE of 26.98 ±16.64 x10^3 versus 44.93 ±19.58 x10^3, P =0.0047). With multivariate analysis, the independent predictors of an SVR were fibrosis of stage F <2 (odds ratio [OR], 13.3; 95% confidence interval [CI], 1.25 to 141.096; P < 0.03) and SE below the median (OR, 5.4; 95% CI, 1.22 to 23.87; P < 0.03). More than the presence of minor mutations at the baseline in plasma or in PBMC, the NS3 viral heterogeneity determined by UDPS is an independent factor for an SVR in previously treated patients receiving triple therapy that includes a PI.&nbsp
Published: 2015

9. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma

Author: Sabine Yerly, Maxime Grude, Audrey Mirand, Philippe Flandre, Anne Maillard, Aurélie Guigon, Sandrine Reigadas, Corinne Amiel, Chakib Alloui, Samira Fafi-Kremer, Stéphanie Haim-Boukobza, Stéphanie Raymond, Anne Signori-Schmuck, Hélène Jeulin, Laurence Morand-Joubert, Virginie Ferré, Catherine Roussel, Brigitte Montes, Pantxika Bellecave, Anne-Geneviève Marcelin, Sophie Vallet, Diane Descamps, Lambert Assoumou, Mary-Anne Trabaud, Vincent Calvez, Cathia Soulié, Francis Barin, Constance Delaugerre, Coralie Pallier, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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, CHU Tenon [AP-HP], CHU Saint-Antoine [AP-HP], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Virologie [Hôpital Paul-Brousse - APHP] (World Health Organization Rubella National Reference Laboratory), Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Service de virologie et unité de surveillance biologique [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Department of Infectious Diseases [Paris], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie CHU de NANCY BRADOIS, Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Geneva University Hospital (HUG), Département de virologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Orléans, Laboratoire de Virologie [Strasbourg], CHU Clermont-Ferrand, CHU Pontchaillou [Rennes], CHU-BREST-Service de Virologie, and CHU Amiens-Picardie
Subjects: Adult, Male, Microbiology (medical), Genotype, Genotyping Techniques, Population, Human immunodeficiency virus (HIV), HIV Infections, Microbial Sensitivity Tests, Drug resistance, Biology, medicine.disease_cause, Plasma, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Viral, HIV encephalitis, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Sida, education, Cognitive impairment, Cerebrospinal Fluid, Retrospective Studies, Pharmacology, education.field_of_study, Middle Aged, Viral Load, biology.organism_classification, Virology, Infectious Diseases, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, France, Viral load, Switzerland, 030217 neurology & neurosurgery
Abstract: International audience; Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations.Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm.Results: Among the 227 studied patients with VL > 1.7 log10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7–4.7) log10 copies/mL] and 32 had discordant VL in plasma (VL 1.7 log10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients.Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.
Published: 2017

10. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma

Author: Françoise Stoll-Keller, Henia Saoudin, Arielle A. Rosenberg, Dominique Bettinger, Pascal Veillon, Odile Petsaris, Cécile Henquell, Bruno Pozzetto, Catherine Gaudy-Graffin, Jean-Baptiste Bour, Sophie Minjolle-Cha, Jacques Izopet, Christopher Payan, E. Bouthry, Alexandra Ducancelle, Adeline Pivert, Hélène Le Guillou-Guillemette, Gisèle Lagathu, Sylvie Larrat, P. André, Anne Signori-Schmuck, Sophie Vallet, Françoise Lunel-Fabiani, Jean-Michel Pawlotsky, Yazid Baazia, Elisabeth André-Garnier, Christophe Lemaire, Florence Abravanel, Pascale Trimoulet, Sophie Alain, Vincent Thibault, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), 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), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Pontchaillou [Rennes], 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), Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôtel-Dieu de Nantes, 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 et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, 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), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), 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)-Centre National de la Recherche Scientifique (CNRS), 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), Université Jean Monnet [Saint-Étienne] (UJM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, 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 de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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 National de la Recherche Scientifique (CNRS), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), and AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA)
Subjects: RNA viruses, 0301 basic medicine, Mutant, lcsh:Medicine, Hepacivirus, Viral Nonstructural Proteins, Biochemistry, Cohort Studies, Database and Informatics Methods, Viral Envelope Proteins, Gene Duplication, Gene duplication, Evolutionary Emergence, lcsh:Science, Homologous Recombination, Pathology and laboratory medicine, Phylogeny, Data Management, Recombination, Genetic, Genetics, Multidisciplinary, Hepatitis C virus, Liver Neoplasms, Phylogenetic Analysis, Medical microbiology, Hepatitis C, 3. Good health, Nucleic acids, Phylogenetics, Viruses, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pathogens, Sequence Analysis, Recombination, Research Article, Computer and Information Sciences, Evolutionary Processes, Carcinoma, Hepatocellular, DNA recombination, Bioinformatics, 030106 microbiology, Viral quasispecies, Biology, Research and Analysis Methods, Microbiology, Viral Evolution, Evolution, Molecular, 03 medical and health sciences, Virology, Humans, Evolutionary Systematics, Gene, DNA sequence analysis, Taxonomy, Medicine and health sciences, Cloning, Evolutionary Biology, Polymorphism, Genetic, Biology and life sciences, Flaviviruses, lcsh:R, Organisms, Viral pathogens, RNA, Bayes Theorem, DNA, Hepatitis viruses, Organismal Evolution, Microbial pathogens, 030104 developmental biology, Genetic Loci, Microbial Evolution, Mutation, lcsh:Q, Homologous recombination, Sequence Alignment
Abstract: International audience; Background: The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies.Methods: Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event.Results: Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients.Conclusions: These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.
Published: 2017

11. Sequencing Assays for Failed Genotyping with the Versant Hepatitis C Virus Genotype Assay (LiPA), Version 2.0

Author: Anne Signori-Schmuck, Katia Fusillier, Jean-Dominique Poveda, Sylvie Larrat, Vincent Thibault, Nelly Magnat, Camille Coudret, and Patrice Morand
Subjects: Adult, Male, Microbiology (medical), Untranslated region, Genotype, Hepacivirus, Hepatitis C virus, Molecular Sequence Data, medicine.disease_cause, chemistry.chemical_compound, Virology, medicine, Humans, False Negative Reactions, NS5B, Genotyping, Aged, Genetics, NS3, Base Sequence, biology, Genetic Variation, Sequence Analysis, DNA, Hepatitis C, Middle Aged, medicine.disease, biology.organism_classification, Molecular Diagnostic Techniques, chemistry, Mutation, RNA, Viral, Female
Abstract: For optimal antiviral therapy, the hepatitis C virus (HCV) genotype needs to be determined, as it remains a strong predictor of sustained viral response. In this study, we assessed the number of HCV genotyping results that could not be determined using the commercially available line probe assay (LiPA) (Versant hepatitis C virus genotype 2.0 assay) in a large international panel of samples from 9,874 HCV-positive patients. In-house sequencing assays targeting the 5′ untranslated region (UTR), core region, NS3 region, and NS5B region of the HCV genome and phylogenetic analyses were used to resolve these LiPA failures. Among all cases, the genotypes of 51 samples (0.52%) could not be determined with the LiPA. These undetermined results were observed more frequently among samples from non-European regions (mainly the Arabian Peninsula). The use of sequencing assays coupled with phylogenetic analysis provided reliable genotype results for 86% of the LiPA failures, which exhibited higher rates of genotypes 4, 5, and 6 than did LiPA-resolved genotypes. As expected, the 5′ UTR was not sufficiently variable for clear discrimination between genotypes 1 and 6, but it also resulted in errors in classification of some genotype 3 and 4 cases using well-known Web-based BLAST programs. This study demonstrates the low frequency of genotyping failures with the Versant hepatitis C virus genotype 2.0 assay (LiPA) and also underlines the need for a complex combination of sequences and phylogenetic analyses in order to genotype these particular HCV strains correctly.
Published: 2013

12. Performance of an antigen–antibody combined assay for hepatitis C virus testing without venipuncture

Author: Marie-Noelle Hilleret, Cécile Bourdon, Cécile Garnaud, Myriam Blanc, Jean-Louis Quesada, Vincent Leroy, Raphaele Germi, P Leclercq, Jean-Pierre Zarski, Monique Baccard, Sophie Mathieu, Sylvie Larrat, Patrice Morand, and Anne Signori-Schmuck
Subjects: Adult, Male, Fingerstick, Point-of-Care Systems, Hepatitis C virus, medicine.disease_cause, Sensitivity and Specificity, Young Adult, Phlebotomy, Antigen, Virology, medicine, Humans, Saliva, Dried blood, Antigens, Viral, Aged, Immunoassay, Venipuncture, biology, Clinical Laboratory Techniques, business.industry, virus diseases, Hepatitis C Antibodies, Middle Aged, Serum samples, Hepatitis C, digestive system diseases, Blood, Infectious Diseases, biology.protein, Female, Antibody, business
Abstract: Background Hepatitis C virus (HCV) is underdiagnosed and therefore increasing the opportunities for HCV testing without venipuncture may be useful. Objectives We evaluated the analytical performance of a modified, commercially available, combined HCV antigen–antibody assay (cEIA) (Monolisa ® HCV-Ag-Ab-ULTRA) and a commercially available point-of-care (POC) device (OraQuick ® HCV) on fingerstick blood (FSB) and oral mucosal transudate (OMT). Study design FSB, OMT and serum samples were collected from 113 cases of HCV-antibody-positive patients and 88 HCV-antibody-negative controls. The HCV-antibody-positive group included 63 patients with quantifiable HCV-RNA (56%) and 17 HIV/HCV co-infected patients (15%). FSB and OMT specimens were collected as dried blood spots (DBSs) or with the OraSure collection system, before testing with cEIA. Results With FSB specimens, the cEIA and the POC device exhibited 100% specificity and 98.2% and 97.4% sensitivity, respectively. The specificity of the cEIA in FSB sharply decreased if stored 3 days at room temperature. With OMT specimens, the cEIA sensitivity (71.7%) and specificity (94.3%) were significantly lower than the performance of OraQuick ® HCV (sensitivity, 94.6%; specificity, 100%). The optical densities obtained with the cEIA in FSB and OMT were lower in HIV/HCV co-infected patients compared with HCV monoinfected patients. Conclusion The cEIA using FSB specimens collected on DBSs preserved in appropriate storage conditions was a reliable alternative, equivalent to the POC assay, for HCV testing without venipuncture. The cEIA was not adapted for HCV testing on OMT.
Published: 2012

13. Ultradeep sequencing of B and non-B HIV-1 subtypes: Viral diversity and drug resistance mutations before and after one month of antiretroviral therapy in naive patients

Author: Michael G. B. Blum, Myriam Blanc, Om Kulkarni, Olivier Epaulard, Anne Signori-Schmuck, Katia Fusillier, Olivier François, Patrice Morand, Sylvie Larrat, and P Leclercq
Subjects: 0301 basic medicine, Adult, Male, Genotype, Anti-HIV Agents, Population, HIV Infections, Drug resistance, Biology, medicine.disease_cause, 03 medical and health sciences, Plasma, immune system diseases, Virology, Antiretroviral Therapy, Highly Active, Genetic variation, Drug Resistance, Viral, medicine, Humans, education, education.field_of_study, Mutation, virus diseases, Genetic Variation, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Middle Aged, Viral Load, Reverse transcriptase, HIV Reverse Transcriptase, CD4 Lymphocyte Count, 030104 developmental biology, Infectious Diseases, HIV-1, Pyrosequencing, RNA, Viral, Reverse Transcriptase Inhibitors, Female, Viral load
Abstract: Background Ultradeep pyrosequencing technologies permit an assessment of the genetic diversity and the presence and frequency of minority variants in a viral population. The effect of these parameters on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients is poorly understood. Objectives The present study used the pyrosequencing Roche 454 prototype assay to determine whether antiretroviral efficacy is correlated with viral diversity and minority drug resistance mutations in HIV-infected treatment-naive patients and to compare assay performance in B and non-B subtypes. Study design The study included 30 HIV-1 infected naive patients (20 with subtype non-B and 10 with subtype B). Ultradeep pyrosequencing of protease and reverse transcriptase genes was performed at baseline and 1 month after HAART initiation. Plasma HIV VL was measured at 0 and after 1, 3, and 6 months of HAART. Results Pre-HAART minority drug resistance mutations were observed to NRTI in 4 patients, to NNRTI in 6 patients, and to PI in 1 patient; there was no difference in HAART-induced VL decay between patients. Pre-HAART diversity was significantly correlated with the time elapsed since HIV-1 infection diagnosis, but not with the subtype, VL, or CD4 count. Patients with an undetectable VL after 3 months of HAART had a higher pre-HAART diversity. Pre- and post-HAART diversities were not statistically different. There was no difference in assay performance between subtype B and non-B. Conclusions A high pre-HAART viral diversity might have a positive effect on the outcome of HAART. Pre-therapeutic minority drug resistance mutations are uncommon in naive patients.
Published: 2016

14. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France

Author: Jacques Izopet, Jacqueline Cottalorda, Vincent Calvez, Charlotte Charpentier, Henia Saoudin, Georges Dos Santos, Mary-Anne Trabaud, Francis Barin, V. Calvez, Cécile Henquell, Delphine Desbois, C. Delaugerre, Slim Fourati, D. Bettinger, Thomas Bourlet, Anne Krivine, Bernard Masquelier, S. Vallet, M. Bouvier-Alias, Catherine Tamalet, B. Masquelier, S. Rogez, Coralie Pallier, J. C. Plantier, C. Charpentier, F. Barin, J. Cottalorda, A. Maillard, Alexandre Storto, G. DosSantos, Chakib Alloui, B. Montes, Marie-Laure Chaix, A. G. Marcelin, Anne Signori-Schmuck, D. Desbois, Anne-Geneviève Marcelin, Marie Laure Chaix, C. Tamalet, F. Brun-Vézinet, Françoise Brun-Vézinet, J. Izopet, Philippe Flandre, G. Anies, Anne Maillard, Diane Descamps, Patrice Andre, Jean-Claude Tardy, Dominique Costagliola, Brigitte Montes, Laurence Morand-Joubert, Annick Ruffault, Jean-Christophe Plantier, Sophie Pakianather, L. Morand-Joubert, and Constance Delaugerre
Subjects: Male, Microbiology (medical), Anti-HIV Agents, HIV Infections, Drug resistance, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, 0302 clinical medicine, HIV Protease, Drug Resistance, Viral, HIV Seropositivity, Prevalence, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, biology, 030306 microbiology, Proteolytic enzymes, biology.organism_classification, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Infectious Diseases, Chronic Disease, Mutation, Immunology, Lentivirus, HIV-1, Reverse Transcriptase Inhibitors, Female, France, Viral disease, Viral load, medicine.drug
Abstract: Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity
Published: 2010

15. Factors Associated with Virological Response to Etravirine in Nonnucleoside Reverse Transcriptase Inhibitor-Experienced HIV-1-Infected Patients

Author: Charlotte Charpentier, Bernard Masquelier, Philippe Flandre, Dominique Bettinger, Cécile Henquell, Vincent Calvez, Annick Ruffault, Georges Dos Santos, Henia Saoudin, Sophie Vallet, Francis Barin, Jacques Izopet, Sylvie Rogez, Diane Descamps, Chakib Alloui, Catherine Tamalet, Anne Signori-Schmuck, Mary-Anne Trabaud, Jacqueline Cottalorda, Constance Delaugerre, Anne-Geneviève Marcelin, Magali Bouvier-Alias, and Laurence Morand-Joubert
Subjects: Male, Oncology, medicine.medical_specialty, Enfuvirtide, Genotype, Anti-HIV Agents, Etravirine, HIV Infections, Biology, Antiviral Agents, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, Interquartile range, Internal medicine, Drug Resistance, Viral, Nitriles, medicine, Humans, Pharmacology (medical), Phylogeny, Darunavir, 030304 developmental biology, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, Reverse Transcriptase Polymerase Chain Reaction, 030306 microbiology, virus diseases, Raltegravir, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Pyridazines, Pyrimidines, Treatment Outcome, Infectious Diseases, Mutation, HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Female, medicine.drug
Abstract: To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log10copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm3(IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log10copies/ml and/or HIV-1 RNA level of
Published: 2010

16. Tipranavir-Ritonavir Genotypic Resistance Score in Protease Inhibitor-Experienced Patients

Author: Jacques Izopet, Gilles Peytavin, Chakib Alloui, Marie-Laure Chaix, Francis Barin, Diane Descamps, Bernard Masquelier, Georges Dos Santos, Anne Signori-Schmuck, Marc Lavignon, Annick Ruffault, Brigitte Montes, Vincent Calvez, Magali Bouvier-Alias, Corinne Amiel, Anne-Geneviève Marcelin, Charlotte Charpentier, and Philippe Flandre
Subjects: Male, Genotype, Anti-HIV Agents, Pyridines, medicine.medical_treatment, HIV Infections, Biology, medicine.disease_cause, Antiviral Agents, HIV Protease, Drug Resistance, Viral, medicine, Humans, HIV Protease Inhibitor, Pharmacology (medical), Protease inhibitor (pharmacology), Pharmacology, Sulfonamides, Mutation, Ritonavir, Protease, HIV Protease Inhibitors, Virology, Infectious Diseases, Pyrones, Enzyme inhibitor, HIV-1, biology.protein, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, Tipranavir, medicine.drug
Abstract: To identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log10in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V − F53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of −1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n= 16, all non-B subtypes considered together) than for those infected with clade B viruses (n= 127) (25% and 59%, respectively;P= 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.
Published: 2008

17. Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients

Author: Elisabeth André-Garnier, J. B. Bour, Jacques Izopet, Christophe Lemaire, S. Vallet, Adeline Pivert, Arielle R. Rosenberg, Pascale Trimoulet, Christopher Payan, E. Bouthry, Pascal Veillon, Sophie Alain, Dominique Bettinger, P. André, Alexandra Ducancelle, Catherine Gaudy-Graffin, Jean-Michel Pawlotsky, Françoise Stoll-Keller, Odile Petsaris, Cécile Henquell, Yazid Baazia, Bruno Pozzetto, Françoise Lunel-Fabiani, Florence Abravanel, Henia Saoudin, V. Thibault, Anne Signori-Schmuck, Sandrine Bertrais, Gisèle Lagathu, H. Le Guillou-Guillemette, Sylvie Larrat, S. Minjolle-Cha, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), CHU Limoges, Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Hôtel-Dieu de Nantes, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Avicenne, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), 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), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Pontchaillou [Rennes], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, The authors thank A. Lefebvre, E. Muel, Y. Desille, I. Renard, A. Plages, A. Rodallec and W. Merrouche for their assistance in clinical data recording.Funding: This study was funded by the ANRS (Agence de Nationale de Recherche sur le VIH et les hépatites, appel d’offre Mars 2006)., PRES Université Nantes Angers Le Mans [UNAM], Interactions cellulaires et applications thérapeutiques (ICAT), Université d'Angers (UA) - CHU Angers - CRLCC Paul Papin - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Service de virologie, Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 (UPS) - IFR30 - IFR150 - Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [APHP], Université européenne de Bretagne (UEB) - Université de Bretagne Occidentale (UBO) - IFR148 ScInBioS, Centre Hospitalier Universitaire de Dijon (CHU Dijon), CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Hospices Civils de Lyon, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université François Rabelais - Tours - CHRU Tours, CHU Besançon, Université de Franche-Comté (UFC), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF) - Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), 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 de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Henri Mondor [Créteil], and Jonchère, Laurent
Subjects: Adult, Liver Cirrhosis, Male, hepatitis C virus, Cirrhosis, Carcinoma, Hepatocellular, Hepatitis C virus, [SDV]Life Sciences [q-bio], Viral quasispecies, Hepacivirus, Biology, Viral Nonstructural Proteins, medicine.disease_cause, NS5A, Liver disease, Virology, Gene Duplication, Gene duplication, medicine, Prevalence, Humans, Aged, Hepatitis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Sequence Analysis, RNA, cirrhosis, Liver Neoplasms, Hepatitis C, hepatocellular carcinoma, Hepatitis C, Chronic, Middle Aged, medicine.disease, digestive system diseases, 3. Good health, Protein Structure, Tertiary, [SDV] Life Sciences [q-bio], Mutagenesis, Insertional, Infectious Diseases, Cross-Sectional Studies, Hepatocellular carcinoma, RNA, Viral, Female, V3 domain, France, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background The NS5A protein of the hepatitis C virus has been shown to be involved in the development of hepatocellular carcinoma. Objectives In a French multicenter study, we investigated the clinical and epidemiological features of a new HCV genotype 1b strain bearing a wide insertion into the V3 domain. Study Design We studied NS5A gene sequences in 821 French patients infected with genotype 1b HCV. Results We identified an uncharacterized V3 insertion without ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino-acids for the majority of patients; 3 patients had 27 amino-acids insertions and 1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids insertions and the V3 domain ranged from 48 to 96% with E-values above 4e-5, thus illustrating sequence homology and a partial gene duplication event that to our knowledge has never been reported in HCV. Moreover we showed the presence of the duplication at the time of infection and its persistence at least during 12 years in the entire quasispecies. No association was found with extrahepatic diseases. Conversely, patients with cirrhosis were two times more likely to have HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in patients with both cirrhosis and HCC, p for trend=0.045). Conclusions We identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time. The duplication may be associated with unfavorable evolution of liver disease including a possible involvement in liver carcinogenesis
Published: 2015

18. HIV-1 Load Comparison Using Four Commercial Real-Time Assays

Author: Thomas Bourlet, Patrice Andre, Henia Saoudin, Vinca Icard, Laurent Roche, Mary-Anne Trabaud, René Ecochard, Anne Signori-Schmuck, Jean-Claude Tardy, Bruno Pozzetto, Patrice Morand, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], 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), and 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)
Subjects: Microbiology (medical), medicine.medical_specialty, Cobas taqman, [SDV]Life Sciences [q-bio], HIV Infections, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Antiretroviral treatment, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, HIV-1 Load, 0303 health sciences, biology, 030306 microbiology, Disease progression, Viral Load, biology.organism_classification, Hiv seropositivity, 3. Good health, Lentivirus, HIV-1, RNA, Viral, Reagent Kits, Diagnostic, Viral load
Abstract: The HIV-1 RNA viral load is commonly used for the monitoring of disease progression and antiretroviral treatment of HIV-1-infected patients. Since the misestimating of values could lead to inappropriate therapeutical management, the comparative performances, especially the ability to span the genetic diversity of HIV-1, of available automated real-time assays need to be evaluated. We conducted a prospective study with 74 consenting patients enrolled between March 2007 and November 2008. A blood sample was obtained at the time of diagnosis of HIV seropositivity and blindly tested for HIV-1 RNA by at least 4 commercial tests: the Abbott m 2000 RealTi m e HIV-1, bioMérieux NucliSens EasyQ HIV-1, version 1.2 (v1.2), and Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) v1.0 and v2.0 assays. The means of difference were null between CAP/CTM v2.0 and Abbott for CRF02_AG subtypes but positive in favor of CAP/CTM v2.0 for genotype B and negative in favor of NucliSens for all genotypes. The standard deviation (SD) of difference ranged from 0.3 to 0.59, depending on the considered couples of assays. Reliabilities of these four tests, appreciated by the standard deviation of difference between the measurement and the estimated “true” viral load and by the coefficient of reliability, were significantly different ( P < 10 −4 ) among each other. Significant differences were also observed within each group of HIV-1 genotype. The global disparity was higher for CRF02_AG than for B subtypes. This study indicates a risk of viral load misestimating or discrepancies between techniques, depending on the HIV-1 subtype, and speaks in favor of using the same assay for the monitoring of HIV-1-infected patients.
Published: 2011

19. Response to HAART in French patients with resistant HIV-1 treated at primary infection: ANRS Resistance Network

Author: Catherine Tamalet, Loïc Desquilbet, Christiane Deveau, Cécile Goujard, Christine Rouzioux, Isabelle Pellegrin, Julie Galimand, Anne Signori-Schmuck, Diane Descamps, Françoise Brun-Vézinet, Marc Wirden, Bernard Masquelier, Laurence Meyer, Véronique Schneider, Marie-Laure Chaix, and Dominique Costagliola
Subjects: Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Virus, Cohort Studies, Acquired immunodeficiency syndrome (AIDS), Immunopathology, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Medicine, Humans, Pharmacology (medical), In patient, Sida, Pharmacology, biology, business.industry, Viral Load, medicine.disease, biology.organism_classification, Antiretroviral therapy, Virology, CD4 Lymphocyte Count, Infectious Diseases, Treatment Outcome, HIV-1, Viral disease, France, business
Abstract: Objective The aim of the study was to analyse the response to highly active antiretroviral therapy (HAART) initiated at the time of primary HIV infection (PHI) in patients infected with a virus resistant to ≥1 drug of their treatment compared with patients infected with a wild-type virus. Methods We analysed data from 350 patients who were enrolled from 1996–2004 in the French ANRS PRIMO Cohort or in the ANRS Resistance Group and treated with HAART during PHI. During the study period, HAART was initiated before the result of the genotypic resistance test was available. We compared patients infected with a virus resistant to ≥1 drug of their regimen (GR group, n=46) with patients harbouring a wild-type virus (WT group, n=304). Virological and immunological response to treatment according to drug-resistance profile was analysed 3 months and 6 months after HAART initiation. Results In GR and WT groups, HIV RNA level was + T-cell count at HAART initiation, patients with virus resistant to ≥1 drug of their regimen were significantly less likely to achieve undetectable viral load at month 3 (odds ratio 0.32, 95% confidence interval 0.15–0.72) than the others. This difference was sustained up to month 6. Conclusion In this large cohort of HAART-treated PHI-patients, the presence of drug resistance mutations led to suboptimal response to early therapy.
Published: 2008

20. French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002

Author: Cécile Poggi, Martine Harzic, Françoise Brun-Vézinet, Evelyne Kohli, Diane Descamps, Patrice Andre, Jacques Izopet, Sylvie Rogez, Didier Ingrand, Jean-Christophe Plantier, Jacqueline Cottalorda, Laurence Meyer, Marie-Laure Chaix, Pierre Palmer, Marc Wirden, Annick Ruffault, Isabelle Pellegrin, Christiane Deveau, Dominique Costagliola, Christine Rouzioux, Said Mouajjah, Anne Signori-Schmuck, Bernard Masquelier, Véronique Brodard, Véronique Schneider, and Catherine Tamalet
Subjects: Male, medicine.medical_specialty, National Health Programs, Anti-HIV Agents, Sexual Behavior, Drug Resistance, HIV Infections, Drug resistance, Cohort Studies, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Epidemiology, Medicine, Humans, Pharmacology (medical), Sida, Acquired Immunodeficiency Syndrome, biology, business.industry, virus diseases, Viral Load, medicine.disease, biology.organism_classification, CD4 Lymphocyte Count, Infectious Diseases, Immunology, Lentivirus, Acute Disease, Chronic Disease, HIV-1, RNA, Viral, Female, Viral disease, France, business, Viral load, Sentinel Surveillance, Cohort study
Abstract: To survey the frequency of genotypic antiretroviral resistance and the spread of non-B subtypes in patients with primary HIV-1 infection (2001-2002) and in treatment-naive chronically HIV-1-infected patients (2001).Plasma samples from 303 patients with acute HIV-1 infection (Primo study) and 363 treatment-naive patients with chronic HIV-1 infection (Odyssee study) were tested for genotypic resistance. Resistance mutations were identified from the International AIDS Society Resistance Testing-USA panel and resistant viruses were defined according to the French Agence Nationale de Recherches sur le SIDA (ANRS) resistance algorithm.In the Primo study, 14% of the patients had viruses with resistance mutations and 12% of patients had viruses with mutations conferring resistance to least 1 antiretroviral drug. Thirty patients had viruses with mutations to at least 1 antiretroviral drug in a single pharmacologic class. Six patients were infected by viruses resistant to 2 or 3 classes of drugs. In the Odyssee study, the prevalence of reverse transcript (RT) associated and major protease inhibitor-associated mutations was 6.1% (95% CI: 3.6-8.6). Six patients had viruses resistant to at least 1 antiretroviral drug and 3 patients had viruses resistant to 2 classes of antiretroviral drugs. Twenty-four percent of acutely infected patients harbored non-B subtype strains (19% in 1999-2000) and 33.2% of chronically infected patients (10% in 1998; P0.0001).In France, the frequency of HIV-1 resistance in untreated patients was not significantly higher in 2001-2002 than in previous surveys while the prevalence of non-B subtypes is increasing.
Published: 2005

21. Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen

Author: Jacqueline Cottalorda, Magali Bouvier-Alias, Cécile Henquell, Mary-Anne Trabaud, Anne-Geneviève Marcelin, Bernard Masquelier, Catherine Tamalet, Jacques Izopet, Laurence Morand-Joubert, Sophie Vallet, Annick Ruffault, Anne Signori-Schmuck, Philippe Flandre, Dominique Bettinger, Constance Delaugerre, Sylvie Rogez, Diane Descamps, and Vincent Calvez
Subjects: Cyclopropanes, Male, Oncology, medicine.medical_specialty, Anti-HIV Agents, Etravirine, HIV Infections, Drug resistance, Treatment failure, 03 medical and health sciences, Text mining, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, Nitriles, medicine, Humans, Pharmacology (medical), Nevirapine, Treatment Failure, Pharmacology, 0303 health sciences, 030306 microbiology, business.industry, 030302 biochemistry & molecular biology, virus diseases, Viral Load, HIV Reverse Transcriptase, Reverse transcriptase, Benzoxazines, 3. Good health, Molecular Typing, Pyridazines, Regimen, Pyrimidines, Infectious Diseases, Alkynes, Mutation, Mutation (genetic algorithm), HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Background The aim of this study was to characterize the mutations selected upon failure on etravirine (ETR)-containing regimen in non-nucleoside reverse transcriptase inhibitors (NNRTIs)-experienced HIV-infected patients and the associated factors. Methods Forty-two patients displaying virological failure after a 6 months ETR-containing regimen were studied. For each patient the reverse transcriptase (RT) sequence at failure was compared with all the RT sequences available before introduction of ETR. The effect of baseline and failure HIV-1 RNA, HIV-1 subtype, baseline number of NNRTI resistance mutations, protease inhibitor and nucleoside RT inhibitor genotypic sensitivity scores, number of new drugs used in the treatment, and previous use of efavirenz or nevirapine on the selection of NNRTI resistance mutations were investigated. Results At failure, 12/42 (29%) patients showed development of at least 1 new NNRTI mutation (7 patients selected 1 mutation and 5 patients 2 mutations). NNRTI mutations selected were V179I (5 patients), V179L (1), V179F (2), L100I (1), K103N (2), Y181C (3), K101E (1), K101R (1) and H221Y (1). Univariate analysis showed that HIV-1 RNA level at failure ( P=0.033) and past exposure to efavirenz ( PConclusion In this study, 29% of viruses from patients experiencing ETR failure selected new NNRTI resistance mutations (at position V179 in 2/3 of cases) in a context of multiple NNRTI resistance mutations.

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21 results on '"Anne Signori-Schmuck"'

1. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma.

2. Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey

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

4. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients

5. 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

6. Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen

7. Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE recombinant

8. Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients

9. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma

10. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma

11. Sequencing Assays for Failed Genotyping with the Versant Hepatitis C Virus Genotype Assay (LiPA), Version 2.0

12. Performance of an antigen–antibody combined assay for hepatitis C virus testing without venipuncture

13. Ultradeep sequencing of B and non-B HIV-1 subtypes: Viral diversity and drug resistance mutations before and after one month of antiretroviral therapy in naive patients

14. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France

15. Factors Associated with Virological Response to Etravirine in Nonnucleoside Reverse Transcriptase Inhibitor-Experienced HIV-1-Infected Patients

16. Tipranavir-Ritonavir Genotypic Resistance Score in Protease Inhibitor-Experienced Patients

17. Identification of a duplicated V3 domain in NS5A associated with cirrhosis and hepatocellular carcinoma in HCV-1b patients

18. HIV-1 Load Comparison Using Four Commercial Real-Time Assays

19. Response to HAART in French patients with resistant HIV-1 treated at primary infection: ANRS Resistance Network

20. French national sentinel survey of antiretroviral drug resistance in patients with HIV-1 primary infection and in antiretroviral-naive chronically infected patients in 2001-2002

21. Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen

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21 results on '"Anne Signori-Schmuck"'

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