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1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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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