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5. A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver

Author

León-Janampa, Nancy, primary, Caballero-Posadas, Ignacio, additional, Barc, Céline, additional, Darrouzain, François, additional, Moreau, Alain, additional, Guinoiseau, Thibault, additional, Gatault, Philippe, additional, Fleurot, Isabelle, additional, Riou, Mickaël, additional, Pinard, Anne, additional, Pezant, Jérémy, additional, Rossignol, Christelle, additional, Gaudy-Graffin, Catherine, additional, Brand, Denys, additional, and Marlet, Julien, additional

Published
2023
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6. Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014–2015

Author

Rouet, François, Nouhin, Janin, Zheng, Du-Ping, Roche, Benjamin, Black, Allison, Prak, Sophearot, Leoz, Marie, Gaudy-Graffin, Catherine, Ferradini, Laurent, Mom, Chandara, Mam, Sovatha, Gautier, Charlotte, Lesage, Gérard, Ken, Sreymom, Phon, Kerya, Kerleguer, Alexandra, Yang, Chunfu, Killam, William, Fujita, Masami, Mean, Chhivun, Fontenille, Didier, Barin, Francis, Plantier, Jean-Christophe, Bedford, Trevor, Ramos, Artur, and Saphonn, Vonthanak

Published
2018

10. A Home-Mailed Versus General Practitioner-Delivered Vaginal Self-Sampling Kit for Cervical Cancer Screening: A Cluster Randomized Controlled Trial with a Cost-Effectiveness Analysis

Author

Boyard, Julie, primary, Caille, Agnès, additional, Brunet-Houdard, Solène, additional, Sengchanh-Vidal, Somany, additional, Giraudeau, Bruno, additional, Marret, Henri, additional, Rolland-Lozachmeur, Ghislaine, additional, Rusch, Emmanuel, additional, Gaudy-Graffin, Catherine, additional, and Haguenoer, Ken, additional

Published
2022
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12. Prevalence, Risk Factors, and Impact of Isolated Antibody to Hepatitis B Core Antigen and Occult Hepatitis B Virus Infection in HIV-1—Infected Pregnant Women

Author

Program for HIV Prevention and Treatment (PHPT-2) group, Khamduang, Woottichai, Ngo-Giang-Huong, Nicole, Gaudy-Graffin, Catherine, Jourdain, Gonzague, Suwankornsakul, Weerapong, Jarupanich, Tapnarong, Chalermpolprapa, Veeradate, Nanta, Sirisak, Puarattana-aroonkorn, Noossara, Tonmat, Sakchai, Lallemant, Marc, Goudeau, Alain, and Sirirungsi, Wasna

Published
2013
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13. Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

Author

Yazdanpanah, Yazdan, DIALLO, Alpha, PAUL, Christelle, MERCIER, Noémie, LE MESTRE, Soizic, PETROV‐SANCHEZ, Ventzislava, ANDREJAK, Claire, CHIROUZE, Catherine, MALVY, Denis, DEPLANQUE, Dominique, DUBOS, François, ROSSIGNOL, Patrick, ETIENNE, Manuel, ROSSIGNOL, Bénédicte, LEVY‐MARCHAL, Claire, GILG, Morgane, GIGANTE, Tristan, Marine, BELUZE, HULOT, Jean‐Sebastien, CHAIR, Anissa, KHALIL, Antoine, VISSEAUX, Benoit, COUFFIGNAL, Camille, ROY, Carine, LAOUÉNAN, Cédric, DA SILVEIRA, Charlene, TARDIVON, Coralie, BACHELET, Delphine, DESCAMPS, Diane, MENTRÉ, France, BOMPART, François, LESCURE, François‐Xavier, PEYTAVIN, Gilles, GORENNE, Isabelle, HOFFMANN, Isabelle, GHOSN, Jade, Christophe LUCET, Jean, TIMSIT, Jean‐François, MULLAERT, Jimmy, BHAVSAR, Krishna, BOUADMA, Lila, TAGHERSET, Lysa, TELLIER, Marie‐Capucine, DEBRAY, Marie‐Pierre, ESPOSITO‐FARESE, Marina, SCHNEIDER, Marion, LE, Minh, ETTALHAOUI, Nadia, SI MOHAMMED, Nassima, GAULT, Nathalie, PEIFFER‐SMADJA, Nathan, KEFIF, Ouifiya, ELOY, Philippine, LE HINGRAT, Quentin, KALI, Sabrina, LARIBI, Samira, TUBIANA, Sarah, TRIOUX, Théo, DUVAL, Xavier, VANEL, Noémie, PICONE, Olivier, BASMACI, Romain, ANGOULVANT, François, KAGUELIDOU, Florentia, PAGES, Justine, VEISLINGER, Aurélie, TUAL, Christelle, PAPADOPOULOS, Aurélie, ESPEROU, Hélène, JAAFOURA, Salma, COUFFIN‐CADIERGUES, Sandrine, COELHO, Alexandra, HOCTIN, Alexandre, DIOUF, Alphonsine, MAMBERT, Marina, GAYMARD, Alexandre, LINA, Bruno, ROSA‐CALATRAVA, Manuel, BOUSCAMBERT, Maude, TERRIER, Olivier, MEZIANE, Amina, DORIVAL, Céline, BENKEROU, Dehbia, TÉOULÉ, François, LINGAS, Guillaume, LE NAGARD, Hervé, GUEDJ, Jérémie, NEANT, Nadège, ABEL, Laurent, KHAN, Coralie, DESVALLÉE, Mathilde, WIEDEMANN, Aurélie, LEVY, Yves, MOUQUET, Hugo, BEHILILL, Sylvie, van der WERF, Sylvie, ENOUF, Vincent, SEMAILLE, Caroline, dORTENZIO, Eric, CERVANTES‐GONZALEZ, Minerva, PUÉCHAL, Oriane, NORET, Marion, RORIZ, Mélanie, RISPAL, Patrick, REDL, Sarah, LEFEBVRE, Laurent, GRANIER, Pascal, MAULIN, Laurence, JOSEPH, Cédric, MOYET, Julien, LION‐DAOLIO, Sylvie, MAHIEU, Rafael, DUCANCELLE, Alexandra, DUBEE, Vincent, SALLABERRY, Stéphane, MANUEL, Aldric, MACHEDA, Gabriel, MAILLET, Mylène, CHANZY, Bruno, GAGNARD, Jean‐Charles, GIORDANO, Guillermo, MOUTON PERROT, Clara, PESTRE, Vincent, FICKO, Cécile, GOMINET, Marie, BOUSQUET, Aurore, VAUCHY, Charline, BOUILLER, Kévin, PAGADOY, Maïder, MARTY‐QUINTERNET, Solène, LEPILLER, Quentin, LE BRIS, Cyril, THILL, Benoit, CASANOVA, Marie‐Laure, LE FALHER, Georges, OZIOL, Eric, CORDEL, Hugues, DOURNON, Nathalie, BOUCHAUD, Olivier, BRICHLER, Ségolène, NGUYEN, Duc, BELLECAVE, Pantxika, CICCONE, Camille, LAFON, Marie‐Edith, GREFFE, Ségolène, BOUISSE, Camille, SEDILLOT, Nicholas, BOUHOUR, Damien, CHASSIN, Camille, LHER, Erwan, ANSART, Séverine, TROMEUR, Cécile, GUELLEC, Dewi, MERCKX, Antoine, DJOSSOU, Felix, PEIGNE, Vincent, PIEROBON, Carola, CARRET, Marie‐Christine, JEGO, Florence, ISNARD, Margaux, AUCHABIE, Johann, COURTOIS, Roxane, LESENS, Olivier, MARTINOT, Martin, LACOSTE, Marie, ELHARRAR, Brigitte, GARRAIT, Valérie, DELACROIX, Isabelle, MAITRE, Thomas, Baptiste ASSIE, Jean, NYAMANKOLLY, Elsa, Xavier CATHERINE, François, BLOT, Mathieu, MAHY, Sophie, BUISSON, Marielle, PIROTH, Lionel, GUILLOTIN, Florence, DE ROUGEMONT, Alexis, CAMPANA, Valentine, PASQUIER, Jérémie, CABIE, André, BESSIS, Simon, EPAULARD, Olivier, TERZI, Nicolas, PAYEN, Jean‐François, BOUILLET, Laurence, HAMIDFAR, Rebecca, Le MARECHAL, Marion, MACHADO, Moïse, BARRELET, Audrey, BEDOSSA, Alexandra, COLIN, Gwenhaël, DECOURS, Romain, GUIMARD, Thomas, GOUJARD, Cécile, JAUREGUIBERRY, Stéphane, CHERET, Antoine, Sophie RESSEGUIER, Anne, POISSY, Julien, MATHIEU, Daniel, NSEIR, Saad, ENGELMANN, Ilka, REMY, Martine, VUOTTO, Fanny, GACHET, Benoit, FAURE, Karine, BOYER‐BESSEYRE, Marielle, Enagnon, Kazali, LAMBERT, Marc, SCHERPEREEL, Arnaud, FRY, Stéphanie, YELNIK, Cécile, BITKER, Laurent, MEZIDI, Mehdi, YONIS, Hodane, BENECH, Nicolas, PERPOINT, Thomas, CONRAD, Anne, ICARD, Vinca, VALETTE, Martine, THIBERVILLE, Simon‐Djamel, REBAUDET, Stanislas, DUSSOL, Bertrand, DIAMANTIS, Sylvain, CHAKVEATZE, Catherine, FLATEAU, Clara, DINOT, Vincent, GACI, Rostane, OUAMARA, Nadia, ILLES, Hajnal‐Gabriela, GERBAUD MORLAES, Louis, DIMET, Jérôme, LE MOING, Vincent, PANSU, Nathalie, LE BIHAN, Clément, MONTES, Brigitte, Sophie BOUREAU, Anne, ALLAVENA, Clotilde, BOUCHEZ, Sabelline, GUERY, Romain, LE TURNIER, Paul, MEAR‐PASSARD, Cécile, FERRE, Virginie, RAPP, Christophe, DEMONCHY, Elisa, MICHELANGELLI, Céline, RISSO, Karine, LOUBET, Paul, LAVIGNE, Jean‐Phillippe, DE MONTMOLLIN, Etienne, PATRIER, Juliette, Henri WICKY, Paul, LE FEVRE, Lucie, JACQUET, Pierre, BORIE, Raphael, DOSSIER, Antoine, LUTON, Dominique, ISERNIA, Valentina, LE GAC, Sylvie, AZOULAY, Cécile, CARLIER, Nicolas, LUONG, Liem, LACHATRE, Marie, LAUNAY, Odile, KERROUMI, Younes, MEYSSONNIER, Vanina, DIEHL, Jean‐Luc, HULOT, Jean‐Sébastien, CHOLLEY, Bernard, ARLET, Jean‐Benoît, SANCHEZ, Olivier, MANDA, Victoria, AZEMAR, Laurène, CASTOR‐ALEXANDRE, Guylaine, LACOMBE, Karine, CHIARABINI, Thibault, LEFEBVRE, Bénédicte, MORAND‐JOUBERT, Laurence, FOFANA, Djeneba, SCHNURIGER, Aurélie, DE CASTRO, Nathalie, DELAUGERRE, Constance, CHAIX, Marie‐Laure, CHAS, Julie, GABORIEAU, Valérie, LE COUSTUMIER, Eve, PICARD, Walter, ZABBE, Jean‐Benoît, PEELMAN, Florent, SOUM, Edouard, AUMAÎTRE, Hugues, CURLIER, Elodie, OUISSA, Rachida, FABRE, Isabelle, RAMMAERT, Blandine, SAIDANI, Nadia, BANI‐SADR, Firouzé, HENTZIEN, Maxime, NGUYEN, Yohan, ROMARU, Juliette, DIDIER, Kévin, ENDERLE, Isabelle, THIBAULT, Vincent, LAINE, Fabrice, LESOUHAITIER, Matthieu, REVEST, Matthieu, TATTEVIN, Pierre, PLANTIER, Jean‐Christophe, LEMEE, Véronique, FERRAND DEVOUGE, Eglantine, ALEXANDRE, Kévin, ARTAUD‐MACCARI, Elise, ALLOU, Nathalie, LAGRANGE, Marie, JABOT, Julien, ROZE, Benoît, BREGEAUD, Delphine, AIT TAMLIHAT, Younes, HACHEMI, Ali, SALVATOR, Hélène, FOURN, Erwan, ZUCMAN, David, DELAVEUVE, Eric, JAUD‐FISCHER, Coline, DUNAND, Paul, BISSUEL, François, DELAVIGNE, Karen, PIEL‐JULIAN, Marie, DELOBEL, Pierre, SARTON, Benjamine, RAFIQ, Marie, MARTIN‐BLONDEL, Guillaume, GUILLEMINAULT, Laurent, MURRIS, Marlène, SOMMET, Agnès, SENNEVILLE, Eric, ROBINEAU, Olivier, MEYBECK, Agnès, GAROT, Denis, PLANTIER, Laurent, GISSOT, Valérie, MARLET, Julien, STEFIC, Karl, GAUDY‐GRAFFIN, Catherine, BARIN, Francis, LEMAIGNEN, Adrien, CORVAISIER, Grégory, LARIVIERE, Delphine, LANGELOT‐RICHARD, Marie, BOTELHO‐NEVERS, Elisabeth, GAGNEUX‐BRUNON, Amandine, TROUILLON, Tiffany, BOURLET, Thomas, PILLET, Sylvie, POZZETTO, Bruno, KIMMOUM, Antoine, LEVY, Bruno, MATTEI, Mathieu, GOEHRINGER, François, RABAUD, Christian, BEVILACQUA, Sibylle, LEFEVRE, Benjamin, GUILLAUMOT, Anne, VENARD, Véronique, JEULIN, Hélène, SCHVOERER, Evelyne, HARTARD, Cédric, CARAUX PAZ, Pauline, RICHIER, Laurent, EL SANHARAWI, Mohamed, 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, ANRS France Recherche Nord & sud Sida-hiv hépatites, France REcherche Nord & sud Sida-hiv Hépatites (FRENSH), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, French COVID cohort study group, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CHU Rouen, Normandie Université (NU), and The Alliance for International Medical Action [Dakar, Sénégal] (ONG ALIMA)

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Adolescent, prospective cohort, SARS‐CoV‐2, Cohort Studies, Young Adult, coronavirus disease 2019, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Risk Factors, Virology, Internal medicine, Diabetes mellitus, emerging infection diseases, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Research Articles, Aged, Aged, 80 and over, SARS-CoV-2, Proportional hazards model, business.industry, Hazard ratio, Age Factors, COVID-19, Middle Aged, Viral Load, medicine.disease, Obesity, Confidence interval, Hospitalization, Infectious Diseases, Female, 030211 gastroenterology & hepatology, France, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID‐19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID‐19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse‐transcriptase polymerase chain reactions virologically confirmed COVID‐19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6–22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56–10.63, p, Highlights Older age, male gender, chronic pulmonary disease (not asthma), obesity, and diabetes were associated with mortality in COVID‐19 hospitalized patients. Viral load at admission decreased with the time since symptom onset, with an association with mortality adjusted on clinical risk factors.

Published
2020

14. A new immunosuppressed pig model to study chronic Hepatitis E infection and the genetic viral diversity

Author

León Janampa, Nancy, Caballero-Posadas, Ignacio, Barc, Céline, Darrouzain, François, Gatault, Philippe, Riou, Mickaël, Pinard, Anne, Pezant, Jérémy, Rossignol, Christelle, Gaudy-Graffin, Catherine, Brand, Denys, Marlet, Julien, and Chanteloup, Nathalie Katy

Subjects
[SDV] Life Sciences [q-bio], Hepatitis E - pig model - Genetic diversity - Innate immune responses - Immunosuppression
Abstract

Introduction and Objectives: Hepatitis E virus (HEV) is a zoonosis associated with chronic hepatitis and cirrhosis in immunocompromised patients. Robust animal models are needed for a better understanding of the pathogenesis of chronic HEV infection. To this aim, we developed a new pig model to characterize the HEV genetic changes associated with chronicity, and the impact of HEV infection on the host innate immune responses. Material and Methods: Twenty piglets were separated into control (n=5), immunocompromised (IC, n=5) and immunocompromised and HEV infected group (IC+HEV, n=10). Pigs were intravenously infected with HEV-3 after two weeks of treatment with immunosuppressive drugs used in kidney transplant recipients (tacrolimus, mycophenolic acid and prednisolone). Pigs were treated and monitored weekly until 11 weeks post infection (wpi). Tacrolimus through concentrations were monitored by HPLCMS/MS (Waters). HEV infection and viral diversity were followed-up by qRT-PCR and NGS analysis (MiSeq, Illumina), respectively. Host innate immune responses were followed-up using DNA array (Fluidigm).Results, Discussion and Conclusion: A unique and relevant animal model of chronic HEV infection was successfully established where 9/10 pigs progressed to chronicity (> 8 wpi) with an inflammatory infiltrate in the liver. Extrahepatic replication in the colon and a unique HEV compartmentalization between sera and feces were observed. One mutation, Y590C (ORF1), was detected (>20%) during the chronic phase in the feces of 6/9 pigs, but not in sera nor in the initial inoculum. Three other mutations were detected (>50%) during the chronic phase: H662L (ORF1, feces), V871A (ORF1, sera) and A639V (ORF2, sera), each in one pig. A pro-inflammatory response and activation of the host innate immune responses (PRR, NF-kB and type I IFN pathways) was observed in blood at acute (4 wpi) and chronic (10 wpi) phases of HEV infection. This systemic inflammation during chronic hepatitis E could be associated with disease progression and/or extrahepatic replication. Contrary, a down-regulation of these pathways was observed in the liver. This suggested a possible inhibition of the host innate immune responses induced by HEV replication. This model could contribute to better understand the pathogenesis of chronic HEV infection and the development of effective therapies.

Published
2022

15. Evolution and phenotypic characterization of HBV quasispecies in compliant patients experiencing unexplained entecavir treatment failure Running title: Entecavir, viral resistance & whole genome

Author

Marlet, Julien, Roch, Emmanuelle, Lier, Clément, Moreau, Alain, Combe, Benjamin, Handala, Lynda, Lefeuvre, Sandrine, Maugey, Morgan, Elkrief, Laure, D’Alteroche, Louis, Potier, Pascal, Brand, Denys, Gaudy-Graffin, Catherine, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional d'Orléans (CHRO), Marlet, Julien, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience; Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present before treatment in patient #1. HBs Ag immune escape mutations were present before treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). These results provided a unique insight into the evolution of HBV quasispecies during entecavir treatment, addressing the whole HBV genome and not only the Pol/RT domain. Our results suggest that mutations selected outside of the Pol/RT domain could contribute to entecavir treatment failure, not by an increased level of resistance, but by an immune escape mechanism, in synergy with immunosuppressive drugs.

Published
2021

16. Modeling Hepatitis E infection in immunocompromised patients using a new pig model

Author

León janampa, Nancy, Barc, Céline, Darrouzain, François, Gatault, Philippe, Riou, Mickaël, Pinard, Anne, Pezant, Jérémy, Caballero-Posadas, Ignacio, Rossignol, Christelle, Gaudy-Graffin, Catherine, Brand, Denys, Marlet, Julien, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Pharmacologie Médicale [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau, Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 Tours (CHRU Tours), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Hepatite E virus, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, animal model, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

18. Antibody Responses after a Third Dose of COVID-19 Vaccine in Kidney Transplant Recipients and Patients Treated for Chronic Lymphocytic Leukemia

Author

Marlet, Julien, primary, Gatault, Philippe, additional, Maakaroun, Zoha, additional, Longuet, Hélène, additional, Stefic, Karl, additional, Handala, Lynda, additional, Eymieux, Sébastien, additional, Gyan, Emmanuel, additional, Dartigeas, Caroline, additional, and Gaudy-Graffin, Catherine, additional

Published
2021
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19. Evolution and phenotypic characterization of whole HBV genome in compliant patients experiencing unexplained entecavir treatment failure

Author

Marlet, Julien, primary, Lier, Clément, additional, Roch, Emmanuelle, additional, Moreau, Alain, additional, Combe, Benjamin, additional, Handala, Lynda, additional, Lefeuvre, Sandrine, additional, Maugey, Morgan, additional, Elkrief, Laure, additional, d’Alteroche, Louis, additional, Potier, Pascal, additional, Brand, Denys, additional, and Gaudy-Graffin, Catherine, additional

Published
2021
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20. Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020

Author

Bal, Antonin, Destras, Gregory, Gaymard, Alexandre, Stefic, Karl, Marlet, Julien, Eymieux, Sébastien, Regue, Hadrien, Semanas, Quentin, d’Aubarede, Constance, Billaud, Geneviève, Laurent, Frédéric, Gonzalez, Claudia, Mekki, Yahia, Valette, Martine, Bouscambert, Maude, Gaudy-Graffin, Catherine, Lina, Bruno, Morfin, Florence, Josset, Laurence, Casalegno, Jean-Sébastien, Frobert, Emilie, Escuret, Vanessa, Icard, Vinca, Jeannoel, Marion, Milon, Marie-Paule, Ramière, Christophe, Scholtès, Caroline, Tardy, Jean-Claude, Trabaud, Mary-Anne, Schuffenecker, Isabelle, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Tours (CHRU Tours), The members of the COVID-Diagnosis HCL Study Group : Jean-Sébastien Casalegno, Emilie Frobert, Vanessa Escuret, Vinca Icard, Marion Jeannoel, Marie-Paule Milon, Christophe Ramière, Caroline Scholtès, Jean-Claude Tardy, Mary-Anne Trabaud, Isabelle Schuffenecker, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Marlet, Julien, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Two step, spike protein, variants, deletion, Genome, Viral, Biology, spike protein, Genome, 03 medical and health sciences, COVID-19, whole genome sequencing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, Spike (database), Base sequence, Sequence Deletion, whole genome sequencing, variants, Base Sequence, deletion, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, 030104 developmental biology, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Identification (biology), France, Rapid Communication
Abstract

International audience; We report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69-V70 (ΔH69/ΔV70), identified in certain SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.

Published
2021

21. Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

Author

Abuduaini, Tuniyazi, primary, Roy, Vincent, additional, Marlet, Julien, additional, Gaudy-Graffin, Catherine, additional, Brand, Denys, additional, Baronti, Cécile, additional, Touret, Franck, additional, Coutard, Bruno, additional, McBrayer, Tamara R., additional, Schinazi, Raymond F., additional, and Agrofoglio, Luigi A., additional

Published
2021
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22. Traitement de l'hépatite B chronique par ténofovir : aspects virologiques et pharmacologiques.

Author

Foucault, Tristan, Handala, Lynda, Paintaud, Gilles, Gaudy-Graffin, Catherine, and Marlet, Julien

Subjects
MULTIDRUG resistance-associated proteins, BIOAVAILABILITY, COGNITIVE therapy, HEPATITIS B, DNA polymerases, HEPATITIS B virus, VIRAL load
Abstract

Résumé: Le ténofovir est un analogue nucléotidique inhibiteur de l'ADN polymérase à activité de transcriptase inverse du virus de l'hépatite B (VHB). Il nécessite une métabolisation intra-cellulaire par des kinases cellulaires pour obtenir la forme triphosphate active. Cette dernière est incorporée à l'ADN viral en cours de synthèse et exerce un effet terminateur de chaîne. Le ténofovir est administré sous forme de promédicaments : le ténofovir disoproxil fumarate (TDF) ou le ténofovir alafénamide (TAF). Le TAF se caractérise par une meilleure tolérance rénale et osseuse que le TDF. Le TDF et le TAF sont indiqués en monothérapie de longue durée pour le traitement de première intention des hépatites B chroniques. Ce traitement permet de prévenir la cirrhose et le carcinome hépatocellulaire qui sont les principales complications de l'hépatite B chronique. Le critère principal de suivi est l'obtention d'une réponse virologique, définie par une charge virale VHB indétectable. Le TDF et le TAF sont associés à des taux de réponse virologique de 64 à 94 % après un an de traitement. Ce taux de réponse dépend de facteurs virologiques, notamment le statut antigène HBe, la charge virale VHB au diagnostic et la présence de certaines mutations dans la polymérase virale (Pol/RT). Aucune résistance au ténofovir n'a été décrite au cours des essais cliniques, ce qui reflète la barrière génétique élevée associée à cette molécule. Néanmoins, les mutations rt181T/V et/ou rtN236T peuvent réduire la sensibilité au ténofovir in vitro et retarder la réponse virologique in vivo. Les mutations CYEI et A194T, récemment décrites, diminuent aussi la sensibilité au ténofovir in vitro mais ne semblent pas avoir d'impact sur la réponse au traitement. La réponse virologique dépend aussi de facteurs de l'hôte, principalement l'observance au traitement, cruciale pour prévenir les complications de l'infection. Cette observance peut être améliorée par des approches comportementales, le soutien d'un tiers ou des rappels par message texte. Enfin, certains polymorphismes génétiques au niveau des transporteurs MRP (multidrug resistance-associated protein)-2 ou MRP4 pourraient moduler la réponse virologique et la tolérance rénale du ténofovir. Dans une perspective de guérison fonctionnelle de l'hépatite chronique B, le ténofovir sera très probablement toujours utilisé, en association avec de nouveaux antiviraux. Pour ces raisons, il semble important de poursuivre l'identification des facteurs pharmacologiques et virologiques associés à la réponse virologique au ténofovir. Tenofovir is a nucleotidic analog inhibitor used in monotherapy as first line treatment of chronic Hepatitis B virus (HBV) infection. This drug requires a two-step phosphorylation by cellular kinases. The active triphosphate form inhibits viral DNA polymerase. Tenofovir has a very low oral bioavailability following oral administration. Hence, its oral administration requires the use of prodrugs: tenofovir disoproxil fumararate (TDF) or tenofovir alafénamide (TAF). TAF demonstrated a lower kidney and bone toxicity than TDF. TAF and TDF treatments allow prevention of chronic hepatitis B complications, which are cirrhosis and hepatocellular carcinoma. Prevention of these complications requires a virological response to the treatment, defined as undetectable HBV DNA. TDF and TAF are associated with virological response rates from 64 to 94 % after one year of treatment. This rate depends on HBV viral load at diagnostic, HBe antigen status, mutations in the HBV polymerase gene (Pol/RT) and patient compliance to the treatment. Tenofovir has a high genetic barrier and resistance mutations to this drug have not yet been described. However, mutations rt181T/V and/or rtN236T have been associated with reduced susceptibility to TDF/TAF in vitro and delayed response in vivo. Recently described mutations CYEI and rtA194T have been associated with reduced susceptibility to TDF/TAF in vitro without any change in viral response in vivo. Patient compliance can be improved using cognitive behavioral therapy, supporter interventions and use of short message service. Finally, some genetic polymorphisms in MRP(multidrug resistance-associated protein)-2 and MRP4 efflux transporters could be associated with TDF toxicity and virological response to TDF or TAF. In the perspective of functional HBV cure, TDF and TAF are likely to be still used, in association with new class of antivirals. For this reason, it is important to further characterize the pharmacological and virological factors associated with partial virological response to tenofovir. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Revisiting HBV resistance to entecavir with a phenotypic approach

Author

Marlet, Julien, primary, Lier, Clément, additional, Roch, Emmanuelle, additional, Maugey, Morgan, additional, Moreau, Alain, additional, Combe, Benjamin, additional, Lefeuvre, Sandrine, additional, d’Alteroche, Louis, additional, Barbereau, Didier, additional, Causse, Xavier, additional, Bastides, Frédéric, additional, Bachelier, Marie-Nadege, additional, Brand, Denys, additional, and Gaudy-Graffin, Catherine, additional

Published
2020
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25. Continuum of hepatitis C care in France: A 20-year cohort study

Author

Hermetet, Coralie, Dubois, Frédéric, Gaudy-Graffin, Catherine, Bacq, Yannick, Royer, Bernard, Gaborit, Christophe, D’Alteroche, Louis, Desenclos, Jean Claude, Roingeard, Philippe, Grammatico-Guillon, Leslie, Khudyakov, Yury, Groupe d'Etudes des Matériaux Hétérogènes (GEMH), Université de Limoges (UNILIM)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours (UT)-EA3856, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-EA3856, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP]

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

26. Suppressive therapy for recurrent cutaneous herpes infections in children under 12 years: An observational study.

Author

Hazard, Margaux, Chinazzo, Marie, Maakaroun‐Vermesse, Zoha, Abasq, Claire, Gaudy‐Graffin, Catherine, Tavernier, Elsa, and Maruani, Annabel

Subjects
HERPES simplex, HERPES labialis
Abstract

Efficacy of suppressive therapy for recurrent HSV infection was assessed by the number of HSV flares under suppressive therapy compared with the number of flares before treatment and the number of flares between children who received suppressive therapy and children who did not. Infections by herpes simplex virus (HSV) are widespread and have a large range of clinical manifestations. There are less data on the treatment of recurrences of HSV infection, especially in children, where very few data are available, and there are no trials neither guidelines. [Extracted from the article]

Published
2022
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28. Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014–2015

Author

Rouet, François, primary, Nouhin, Janin, primary, Zheng, Du-Ping, primary, Roche, Benjamin, primary, Black, Allison, primary, Prak, Sophearot, primary, Leoz, Marie, primary, Gaudy-Graffin, Catherine, primary, Ferradini, Laurent, primary, Mom, Chandara, primary, Mam, Sovatha, primary, Gautier, Charlotte, primary, Lesage, Gérard, primary, Ken, Sreymom, primary, Phon, Kerya, primary, Kerleguer, Alexandra, primary, Yang, Chunfu, primary, Killam, William, primary, Fujita, Masami, primary, Mean, Chhivun, primary, Fontenille, Didier, primary, Barin, Francis, primary, Plantier, Jean-Christophe, primary, Bedford, Trevor, primary, Ramos, Artur, primary, and Saphonn, Vonthanak, primary

Published
2017
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29. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma

Author

Le Guillou-Guillemette, Hélène, primary, Pivert, Adeline, additional, Bouthry, Elise, additional, Henquell, Cécile, additional, Petsaris, Odile, additional, Ducancelle, Alexandra, additional, Veillon, Pascal, additional, Vallet, Sophie, additional, Alain, Sophie, additional, Thibault, Vincent, additional, Abravanel, Florence, additional, Rosenberg, Arielle A., additional, André-Garnier, Elisabeth, additional, Bour, Jean-Baptiste, additional, Baazia, Yazid, additional, Trimoulet, Pascale, additional, André, Patrice, additional, Gaudy-Graffin, Catherine, additional, Bettinger, Dominique, additional, Larrat, Sylvie, additional, Signori-Schmuck, Anne, additional, Saoudin, Hénia, additional, Pozzetto, Bruno, additional, Lagathu, Gisèle, additional, Minjolle-Cha, Sophie, additional, Stoll-Keller, Françoise, additional, Pawlotsky, Jean-Michel, additional, Izopet, Jacques, additional, Payan, Christopher, additional, Lunel-Fabiani, Françoise, additional, and Lemaire, Christophe, additional

Published
2017
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31. Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors

Author

Forconi, Catherine, primary, Gatault, Philippe, additional, Miquelestorena-Standley, Elodie, additional, Noble, Johan, additional, Al-Hajj, Sally, additional, Guillemain, Romain, additional, Stern, Marc, additional, Hoffmann, Thomas, additional, Prat, Louis, additional, Suberbielle, Caroline, additional, Masson, Emeline, additional, Cesbron-Gautier, Anne, additional, Gaudy-Graffin, Catherine, additional, Goudeau, Alain, additional, Thibault, Gilles, additional, Ivanes, Fabrice, additional, Guibon, Roseline, additional, Kazma, Ihab, additional, Lebranchu, Yvon, additional, Büchler, Matthias, additional, Magnan, Antoine, additional, Halimi, Jean-Michel, additional, and Baron, Christophe, additional

Published
2017
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32. Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

Author

Larrat, Sylvie, Vallet, Sophie, David-Tchouda, Sandra, Caporossi, Alban, Margier, Jennifer, Ramière, Christophe, Scholtès, Caroline, Haïm-Boukobza, Stéphanie, Roque-Afonso, Anne-Marie, Besse, Bernard, André-Garnier, Elisabeth, Mohamed, Sofiane, Halfon, Philippe, Pivert, Adeline, Leguillou-Guillemette, Hélène, Abravanel, Florence, Guivarch, Matthieu, Mackiewicz, Vincent, Lada, Olivier, Mourez, Thomas, Plantier, Jean-Christophe, Baazia, Yazid, Alain, Sophie, Hantz, Sébastien, Thibault, Vincent, Gaudy-Graffin, Catherine, Bouvet, Dorine, Mirand, Audrey, Henquell, Cécile, Gozlan, Joël, Lagathu, Gisèle, Pronier, Charlotte, Velay, Aurélie, SCHVOERER, Evelyne, Trimoulet, Pascale, Fleury, Hervé, Bouvier-Alias, Magali, BROCHOT, Etienne, Duverlie, Gilles, Maylin, Sarah, Gouriou, Stéphanie, Pawlotsky, Jean-Michel, Morand, Patrice, Plantier, Christophe, Tang, Y.-W., Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Hôtel-Dieu de Nantes, Alphabio Laboratory, Hôpital Européen [Fondation Ambroise Paré - Marseille], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150) (CPTP), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, Centre de recherche sur l'Inflammation (CRI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Université de Limoges (UNILIM), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, CHU Pontchaillou [Rennes], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et pathogénie des infections à entérovirus (EPIE), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [APHP], Virology Laboratory, General Hospital Papageorgiou, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de Virologie clinique et fondamentale EA 4294, CHU Amiens-Picardie, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie moléculaire et structurale, CHU Grenoble, Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité d'évaluation clinique et médico-économique [CHU Grenoble] (Département de la recherche clinique et de l'innovation), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Virologie [Villejuif], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Laboratoire de Virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ALPHABIO - Laboratoire de biologie médicale, Laboratoire de virologie [CHU Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Virologie [CHU Purpan, Toulouse], Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre national de référence du VIH INSERM U966, Université de Tours (UT), CHU Clermont-Ferrand, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Virologie [Rennes] = Virology [Rennes], Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de bactériologie - hygiène [CHU Amiens], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Unit for Virus Host-Cell Interactions [Grenoble] ( UVHCI ), Université Joseph Fourier - Grenoble 1 ( UJF ) -European Molecular Biology Laboratory [Grenoble] ( EMBL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne ( LUBEM ), Université de Brest ( UBO ), ThEMAS, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Institut d'Enseignement Supérieur et de Recherche en Alimentation, Santé Animale, Sciences Agronomiques et de l'Environnement ( VetAgro Sup ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Institut d'Enseignement Supérieur et de Recherche en Alimentation, Santé Animale, Sciences Agronomiques et de l'Environnement ( VetAgro Sup ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -CHU Grenoble, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-CHU Grenoble, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Grenoble Alpes - UFR Médecine ( UGA UFRM ), Université Grenoble Alpes ( UGA ), Internal Medicine and Infectious Diseases Department, European Hospital and Alphabio Laboratory, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Hôpital Bichat - Claude Bernard, Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche Biomédicale des Armées ( IRBA ), CHU Avicenne, Service de virologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -CHU Pitié-Salpêtrière [APHP], Morphogénèse et antigénicité du VIH et du virus des Hépatites ( MAVIVH ), Université de Tours-Centre Hospitalier Régional Universitaire de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Calcul de l'IN2P3 ( CC-IN2P3 ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Strasbourg, Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Microbiologie cellulaire et moléculaire et pathogénicité ( MCMP ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Faculté de Médecine, CHU Henri Mondor, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, SCHVOERER, Evelyne, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Université de Tours

Subjects
Male, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Hepacivirus, MESH: Treatment Outcome, MESH: Inhibitory Concentration 50, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Aged, education.field_of_study, MESH: Drug Resistance, Viral, MESH: Middle Aged, MESH: Protease Inhibitors, Hepatitis C, Middle Aged, 3. Good health, MESH: Hepatitis C, Chronic, Treatment Outcome, MESH: Oligopeptides, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, MESH: Interferon-alpha, Viral load, Oligopeptides, medicine.drug, Microbiology (medical), MESH: Antiviral Agents, Adult, medicine.medical_specialty, Proline, Hepatitis C virus, Population, Mutation, Missense, Antiviral Agents, Inhibitory Concentration 50, MESH: Ribavirin, Internal medicine, Boceprevir, Virology, Drug Resistance, Viral, Ribavirin, medicine, Humans, Protease Inhibitors, education, Aged, Retrospective Studies, MESH: Mutation, Missense, MESH: Humans, MESH: Proline, business.industry, Interferon-alpha, MESH: Adult, MESH: Retrospective Studies, Hepatitis C, Chronic, medicine.disease, MESH: Male, chemistry, Immunology, MESH: Viral Nonstructural Proteins, business, MESH: Female, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of 3-fold shift in 50% inhibitory concentration (IC 50 ) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) ( P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.

Published
2015

33. Viral sequence variation in chronic carriers of hepatitis C virus has a low impact on liver steatosis.: HCV variability and steatosis

Author

Depla, Marion, D'Alteroche, Louis, Le Gouge, Amélie, Alain, Moreau, Hourioux, Christophe, Meunier, Jean-Christophe, Gaillard, Julien, De Muret, Anne, Bacq, Yannick, Kazemi, Farhad, Avargues, Aurélie, Roch, Emmanuelle, Piver, Eric, Gaudy-Graffin, Catherine, Giraudeau, Bruno, Roingeard, Philippe, Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours-EA3856, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Cellulaire, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), PPF Analyse des Systèmes Biologiques (ASB), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Plate-Forme des Microscopies, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatogastroentérologie, Centre Hospitalier de Blois (CHB), Service de Bactériologie-Virologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, This work was supported by grants from INSERM-DHOS 'Recherche Translationnelle: Virostéatose' and by the 'Ligue Contre le Cancer' (Loir et Cher and Ile et Vilaine). M.D. was supported by a fellowship from INSERM-Région Centre and the 'Fondation pour la Recherche Médicale'. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., and Université de Tours (UT)-EA3856

Subjects
MESH: Viral Core Proteins, viruses, lipid droplet, MESH: Amino Acid Sequence, liver, MESH: Genotype, MESH: Biopsy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, steatosis, MESH: Hepacivirus, MESH: Genetic Variation, MESH: Phylogeny, MESH: Fatty Liver, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Molecular Sequence Data, MESH: Conserved Sequence, electron microscopy, MESH: Host-Pathogen Interactions, MESH: Adult, MESH: Male, MESH: Hepatitis C, Chronic, HCV, MESH: Viral Nonstructural Proteins, MESH: Female, MESH: Liver
Abstract

International audience; Most clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses.

Published
2012

35. CMV‐infected kidney grafts drive the expansion of blood‐borne CMV‐specific T cells restricted by shared class I HLAmolecules via presentation on donor cells

Author

Gatault, Philippe, Al‐Hajj, Sally, Noble, Johan, Chevallier, Eloi, Piollet, Marie, Forconi, Catherine, Gaudy‐Graffin, Catherine, Thibault, Gilles, Miquelestorena‐Standley, Elodie, Halimi, Jean‐Michel, Büchler, Matthias, Lemoine, Roxane, and Baron, Christophe

Abstract

We aimed to determine the role of cytomegalovirus (CMV)‐infected donor cells in the development of a CMV‐specific immune response in kidney transplant recipients. We assessed the CMVpp65‐specific immune response by using interferon‐ɣ ELISPOTand dextramers in peripheral blood mononuclear cells from 115 recipients (D+R− 31, D+R + 44, D−R + 40) late after transplantation (mean 59 ± 42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN‐ɣ‐producing anti‐CMVT cells (P= .004). This effect disappeared with the absence of shared HLAclass I specificities between donors and recipients (P= .430). To confirm the role of donor cells in stimulating the expansion of newly developed CMV‐specific CD8+T cells after transplantation, we compared the number of HLA‐A2–restricted CMV‐specific CD8+T cells in primo‐infected recipients who received an HLA‐A2 or non–HLA‐A2 graft. The median of anti‐CMVpp65 T cells restricted by HLA‐A2 was very low for patients who received a non–HLA‐A2 graft vs an HLA‐A2 graft (300 [0‐14638] vs. 17972 [222‐85594] anti‐CMVpp65 CD8+T cells/million CD8+T cells, P= .001). This adds new evidence that CMV‐infected kidney donor cells present CMVpeptides and drive an inflation of memory CMV‐specific CD8+T cells, likely because of frequent CMVreplications within the graft. Donor cytomegalovirus (CMV) infection affects the CMV‐specific immune response and donor‐shared HLA‐I is crucial for the development of CMV‐specific CD8+ T cells, suggesting that CMV‐infected kidney donor cells present CMV peptides and drive an inflation in memory CMV‐specific T cells.

Published
2018
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36. Sequence and Functional Analysis of the Envelope Glycoproteins of Hepatitis C Virus Variants Selectively Transmitted to a New Host

Author

D'Arienzo, Valentina, primary, Moreau, Alain, additional, D'Alteroche, Louis, additional, Gissot, Valérie, additional, Blanchard, Emmanuelle, additional, Gaudy-Graffin, Catherine, additional, Roch, Emmanuelle, additional, Dubois, Frédéric, additional, Giraudeau, Bruno, additional, Plantier, Jean-Christophe, additional, Goudeau, Alain, additional, Roingeard, Philippe, additional, and Brand, Denys, additional

Published
2013
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37. Analysis of residual perinatal transmission of hepatitis B virus (HBV) and of genetic variants in human immunodeficiency virus and HBV co-infected women and their offspring

Author

Khamduang, Woottichai, primary, Gaudy-Graffin, Catherine, additional, Ngo-Giang-Huong, Nicole, additional, Jourdain, Gonzague, additional, Moreau, Alain, additional, Borkird, Thitiporn, additional, Layangool, Prapaisri, additional, Kamonpakorn, Nareerat, additional, Jitphiankha, Weerachai, additional, Kwanchaipanich, Ratchanee, additional, Potchalongsin, Sathit, additional, Lallemant, Marc, additional, Sirirungsi, Wasna, additional, and Goudeau, Alain, additional

Published
2013
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39. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study

Author

Thibault, Vincent, primary, Gaudy-Graffin, Catherine, additional, Colson, Philippe, additional, Gozlan, Joël, additional, Schnepf, Nathalie, additional, Trimoulet, Pascale, additional, Pallier, Coralie, additional, Saune, Karine, additional, Branger, Michel, additional, Coste, Marianne, additional, and Thoraval, Francoise Roudot, additional

Published
2013
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41. Interpretation of Real-Time PCR Results for Hepatitis C Virus RNA When Viral Load Is Below Quantification Limits

Author

Laperche, Syria, primary, Bouchardeau, Françoise, additional, André-Garnier, Elisabeth, additional, Thibault, Vincent, additional, Roque-Afonso, Anne-Marie, additional, Trimoulet, Pascale, additional, Colimon, Ronald, additional, Duverlie, Gilles, additional, Leguillou-Guillemette, Hélène, additional, Lunel, Françoise, additional, Bouvier-Alias, Magali, additional, Pawlotsky, Jean-Michel, additional, Henquell, Cécile, additional, Schvoerer, Evelyne, additional, Stoll-Keller, Françoise, additional, Chaix, Marie-Laure, additional, Branger, Michel, additional, Gaudy-Graffin, Catherine, additional, Rosenberg, Arielle R., additional, Pozzetto, Bruno, additional, Vallet, Sophie, additional, Baazia, Yazid, additional, Izopet, Jacques, additional, and Lefrère, Jean-Jacques, additional

Published
2011
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43. Transmission of Hepatitis B virus (HBV) minor variants in children born to HBV/HIV co-infected mothers

Author

Khamduang, Woottichai, primary, Gaudy-Graffin, Catherine, additional, Moreau, Alain, additional, Ngo-Giang-Huong, Nicole, additional, Jourdain, Gonzague, additional, Lallemant, Marc, additional, Pipatnakulchai, Surachai, additional, Putiyanun, Chaiwat, additional, Kunkongkapan, Sura, additional, Wannarit, Pornpun, additional, Sirinontakan, Surat, additional, Ardong, Wanna, additional, Sirirungsi, Wasna, additional, and Goudeau, Alain, additional

Published
2009
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46. Multicenter Trials Need To Use the Same Assay for Hepatitis C Virus Viral Load Determination

Author

Laperche, Syria, primary, Bouchardeau, Françoise, additional, Thibault, Vincent, additional, Pozzetto, Bruno, additional, Vallet, Sophie, additional, Rosenberg, Arielle R., additional, Roque-Afonso, Anne-Marie, additional, Gassin, Michèle, additional, Stoll-Keller, Françoise, additional, Trimoulet, Pascale, additional, Gault, Elyanne, additional, Chanzy, Bruno, additional, Mercier, Bernard, additional, Branger, Michel, additional, Pawlotsky, Jean-Michel, additional, Henquell, Cécile, additional, Lunel, Françoise, additional, Gaudy-Graffin, Catherine, additional, Alain, Sophie, additional, Chaix, Marie-Laure, additional, Duverlie, Gilles, additional, Izopet, Jacques, additional, and Lefrère, Jean-Jacques, additional

Published
2007
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47. Prevalence, Risk Factors, and Impact of Isolated Antibody to Hepatitis B Core Antigen and Occult Hepatitis B Virus Infection in HIV-1–Infected Pregnant Women.

Author

Khamduang, Woottichai, Ngo-Giang-Huong, Nicole, Gaudy-Graffin, Catherine, Jourdain, Gonzague, Suwankornsakul, Weerapong, Jarupanich, Tapnarong, Chalermpolprapa, Veeradate, Nanta, Sirisak, Puarattana-aroonkorn, Noossara, Tonmat, Sakchai, Lallemant, Marc, Goudeau, Alain, and Sirirungsi, Wasna

Subjects
HEPATITIS B, IMMUNOGLOBULINS, HIV infections, PREGNANT women, ANTIGENS
Abstract

Among hepatitis B (HB) surface antigen–negative/human immunodeficiency virus–infected pregnant women in Thailand, 14% had isolated antibody to HB core antigen (anti-HBc); of whom 24% had occult HB virus (HBV) infection with low HBV DNA levels. None transmitted HBV to their infants.Background. Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)–infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants.Methods. HIV-1–infected and HBV surface antigen (HBsAg)–negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection.Results. Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%–15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti–hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%–30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%–3.5%) of HIV-1–infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants.Conclusions. HIV-1–infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants. [ABSTRACT FROM AUTHOR]

Published
2013

48. Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand.

Author

Khamduang, Woottichai, Gaudy-Graffin, Catherine, Ngo-Giang-Huong, Nicole, Jourdain, Gonzague, Moreau, Alain, Luekamlung, Nuananong, Halue, Guttiga, Buranawanitchakorn, Yuwadee, Kunkongkapan, Sura, Buranabanjasatean, Sudanee, Lallemant, Marc, Sirirungsi, Wasna, and Goudeau, Alain

Subjects
*HIV, *HEPATITIS B virus, *ANTIRETROVIRAL agents, *LAMIVUDINE, *METHODOLOGY, *KAPLAN-Meier estimator
Abstract

Background: Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log10 IU/mL and 4.47 log10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions: All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of coinfected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC. [ABSTRACT FROM AUTHOR]

Published
2012
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49. Multicenter Quality Control of Hepatitis C Virus Protease Inhibitor Resistance Genotyping

Author

Vallet, Sophie, Larrat, Sylvie, Laperche, Syria, Le Guillou-Guillemette, Hélène, Legrand-Abravanel, Florence, Bouchardeau, Françoise, Pivert, Adeline, Henquell, Cécile, Mirand, Audrey, André-Garnier, Elisabeth, Giordanengo, Valérie, Lagathu, Gisèle, Thibault, Vincent, Scholtes, Caroline, Schvoerer, Evelyne, Gaudy-Graffin, Catherine, Maylin, Sarah, Trimoulet, Pascale, Brochot, Etienne, Hantz, Sébastien, Gozlan, Joël, Roque-Afonso, Anne-Marie, Soussan, Patrick, Plantier, Jean-Christophe, Charpentier, Charlotte, Chevaliez, Stéphane, Colson, Philippe, Mackiewicz, Vincent, Aguilera, Lina, Rosec, Sylvain, Gouriou, Stéphanie, Magnat, Nelly, Lunel-Fabiani, Françoise, Izopet, Jacques, Morand, Patrice, Payan, Christopher, and Pawlotsky, Jean-Michel

Abstract

ABSTRACTHepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

Published
2013
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50. Treatment of chronic hepatitis B: virological and pharmacological aspects

Author

Foucault T, Handala L, Paintaud G, Gaudy-Graffin C, and Marlet J

Subjects
Adenine therapeutic use, Alanine therapeutic use, Antiviral Agents adverse effects, Humans, Tenofovir adverse effects, Hepatitis B, Chronic drug therapy
Abstract

Tenofovir is a nucleotidic analog inhibitor used in monotherapy as first line treatment of chronic Hepatitis B virus (HBV) infection. This drug requires a two-step phosphorylation by cellular kinases. The active triphosphate form inhibits viral DNA polymerase. Tenofovir has a very low oral bioavailability following oral administration. Hence, its oral administration requires the use of prodrugs: tenofovir disoproxil fumararate (TDF) or tenofovir alafénamide (TAF). TAF demonstrated a lower kidney and bone toxicity than TDF. TAF and TDF treatments allow prevention of chronic hepatitis B complications, which are cirrhosis and hepatocellular carcinoma. Prevention of these complications requires a virological response to the treatment, defined as undetectable HBV DNA. TDF and TAF are associated with virological response rates from 64 to 94 % after one year of treatment. This rate depends on HBV viral load at diagnostic, HBe antigen status, mutations in the HBV polymerase gene (Pol/RT) and patient compliance to the treatment. Tenofovir has a high genetic barrier and resistance mutations to this drug have not yet been described. However, mutations rt181T/V and/or rtN236T have been associated with reduced susceptibility to TDF/TAF in vitro and delayed response in vivo. Recently described mutations CYEI and rtA194T have been associated with reduced susceptibility to TDF/TAF in vitro without any change in viral response in vivo. Patient compliance can be improved using cognitive behavioral therapy, supporter interventions and use of short message service. Finally, some genetic polymorphisms in MRP(multidrug resistance-associated protein)-2 and MRP4 efflux transporters could be associated with TDF toxicity and virological response to TDF or TAF. In the perspective of functional HBV cure, TDF and TAF are likely to be still used, in association with new class of antivirals. For this reason, it is important to further characterize the pharmacological and virological factors associated with partial virological response to tenofovir.

Published
2022
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