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1. Comparison of Dual Monoclonal Antibody Therapies for COVID-19 Evolution: A Multicentric Retrospective Study

Author: Karen Zafilaza, Jonathan Bellet, Aurélie Truffot, Vincent Foulongne, Manuela Mireille Onambele, Maud Salmona, Camille Vellas, Claire Périllaud-Dubois, Audrey Mirand, Elisabeth André-Garnier, Enagnon Kazali Alidjinou, Ségolène Brichler, Honorine Fenaux, Magali Bouvier-Alias, Cédric Hartard, Céline Dorival, Fabrice Carrat, Anne-Geneviève Marcelin, Karl Stefic, and Cathia Soulie
Subjects: COVID-19, SARS-CoV-2, monoclonal antibody therapy, spike gene, immune escape mutation, Microbiology, QR1-502
Abstract: Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group.
Published: 2024
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2. Performance of 22 Rapid Lateral Flow Tests for SARS-CoV-2 Antigen Detection and Influence of 'Variants of Concern': Implications for Clinical Use

Author: Aurélie Gourgeon, Alexandre Soulier, Étienne Audureau, Souraya Khouider, Arnaud Galbin, Camille Langlois, Magali Bouvier-Alias, Christophe Rodriguez, Stéphane Chevaliez, Jean-Michel Pawlotsky, and Slim Fourati
Subjects: lateral-flow tests, SARS CoV-2, variants of concern, Microbiology, QR1-502
Abstract: ABSTRACT Large-scale head-to-head assessment of the performance of lateral-flow tests (LFTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen is required in the context of the continuous emergence of new viral variants. The aim of this study was to evaluate the performance of 22 rapid LFTs for the detection of SARS-CoV-2 antigens. The clinical performance of 22 LFTs was evaluated in 1,157 samples collected in the Greater Paris area. The 8 best-performing LFTs were further assessed for their ability to detect 4 variants of concern (VOC), including the alpha, beta, delta, and omicron (BA.1) variants. The specificity of SARS-CoV-2 LFTs was generally high (100% for 15 of them) but was insufficient ( 30 in 32% of samples) during the two first days following symptom onset. Several LFTs exhibited satisfactory sensitivity and specificity, whereas a few others yielded an unacceptable proportion of false-positive results and/or lacked sensitivity. The sensitivity of the best-performing assays was not influenced by VOC, including alpha, beta, delta, and omicron variants. The ability of LFTs to detect the omicron variant could be reduced during the first days following symptom onset due to lower viral loads than with other variants. IMPORTANCE The use of lateral-flow tests (LFTs) to detect SARS-CoV-2 has expanded worldwide. LFTs detect SARS-CoV-2 viral antigen and are less sensitive than nucleic acid amplification testing (NAAT). Their performance must be evaluated independently of the manufacturers. Our study assessed the performance of 22 SARS-CoV-2 antigen LFTs in large panels of well-characterized samples. The majority of LFTs tested exhibited satisfactory sensitivity and specificity, while some assays yielded unacceptable proportions of false-positive results, and others lacked sensitivity for samples containing large amounts of virus. The sensitivity of the best-performing assays did not vary according to the VOC, including the alpha, beta, delta, and omicron variants.
Published: 2022
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3. Diagnosis and Monitoring of Hepatitis B Virus Infection Using the Cobas® HBV Test for Use on the Cobas® 4800 System

Author: Valérie Ortonne, Mélanie Wlassow, Magali Bouvier-Alias, Giovana Melica, Jean-Dominique Poveda, Syria Laperche, Jean-Michel Pawlotsky, and Stephane Chevaliez
Subjects: hepatitis B virus, HBV DNA, HBV monitoring, real-time PCR, hepatitis B infection diagnosis, Biology (General), QH301-705.5
Abstract: (1) Background: Sensitive and accurate nucleic acid amplification technologies are now recommended for hepatitis B virus (HBV) DNA detection and quantification in clinical practice to diagnose and monitor hepatitis B infection. The aim of this study was to assess the analytical and clinical performance of the cobas® HBV Test on the cobas® 4800 System. (2) Methods: Standard panel and clinical specimens were tested in parallel with three different real-time commercial PCR assays including the cobas ® HBV Test, the Cobas® AmpliPrep/Cobas® TaqMan HBV Test v2.0 and Alinity™ m HBV assay. (3) Results: The specificity of the cobas® HBV Test was 97.9%. The limit of detection was estimated to be 2.1 IU/mL. Intra-assay and interassay coefficients of variation varied from 0.14% to 1.92% and 2.16% to 12.02%, respectively. HBV DNA levels in patients infected with different HBV genotypes strongly correlated with those measured by the two other commercial comparators assays. (4) Conclusions: The cobas® HBV Test can be confidently used to detect and accurately quantify HBV DNA in clinical practice as well as in clinical trials with the new anti-HBV drugs currently in development.
Published: 2021
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4. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion.

Author: Juliana Bruder Costa, Tania Dufeu-Duchesne, Vincent Leroy, Inga Bertucci, Magali Bouvier-Alias, Noelle Pouget, Ophelie Brevot-Lutton, Marc Bourliere, Fabien Zoulim, Joel Plumas, Caroline Aspord, and ANRS HB06 PEGAN study group
Subjects: Medicine, Science
Abstract: Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment.
Published: 2016
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5. Hepatitis C virus (HCV) genotype 1 subtype identification in new HCV drug development and future clinical practice.

Author: Stéphane Chevaliez, Magali Bouvier-Alias, Rozenn Brillet, and Jean-Michel Pawlotsky
Subjects: Medicine, Science
Abstract: BackgroundWith the development of new specific inhibitors of hepatitis C virus (HCV) enzymes and functions that may yield different antiviral responses and resistance profiles according to the HCV subtype, correct HCV genotype 1 subtype identification is mandatory in clinical trials for stratification and interpretation purposes and will likely become necessary in future clinical practice. The goal of this study was to identify the appropriate molecular tool(s) for accurate HCV genotype 1 subtype determination.Methodology/principal findingsA large cohort of 500 treatment-naïve patients eligible for HCV drug trials and infected with either subtype 1a or 1b was studied. Methods based on the sole analysis of the 5' non-coding region (5'NCR) by sequence analysis or reverse hybridization failed to correctly identify HCV subtype 1a in 22.8%-29.5% of cases, and HCV subtype 1b in 9.5%-8.7% of cases. Natural polymorphisms at positions 107, 204 and/or 243 were responsible for mis-subtyping with these methods. A real-time PCR method using genotype- and subtype-specific primers and probes located in both the 5'NCR and the NS5B-coding region failed to correctly identify HCV genotype 1 subtype in approximately 10% of cases. The second-generation line probe assay, a reverse hybridization assay that uses probes targeting both the 5'NCR and core-coding region, correctly identified HCV subtypes 1a and 1b in more than 99% of cases.Conclusions/significanceIn the context of new HCV drug development, HCV genotyping methods based on the exclusive analysis of the 5'NCR should be avoided. The second-generation line probe assay is currently the best commercial assay for determination of HCV genotype 1 subtypes 1a and 1b in clinical trials and practice.
Published: 2009
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6. Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination

Author: Aurélien Sokal, Paul Bastard, Pascal Chappert, Giovanna Barba-Spaeth, Slim Fourati, Alexis Vanderberghe, Pauline Lagouge-Roussey, Isabelle Meyts, Adrian Gervais, Magali Bouvier-Alias, Imane Azzaoui, Ignacio Fernández, Andréa de la Selle, Qian Zhang, Lucy Bizien, Isabelle Pellier, Agnès Linglart, Anya Rothenbuhler, Estelle Marcoux, Raphael Anxionnat, Nathalie Cheikh, Juliane Léger, Blanca Amador-Borrero, Fanny Fouyssac, Vanessa Menut, Jean-Christophe Goffard, Caroline Storey, Caroline Demily, Coralie Mallebranche, Jesus Troya, Aurora Pujol, Marie Zins, Pierre Tiberghien, Paul E. Gray, Peter McNaughton, Anna Sullivan, Jane Peake, Romain Levy, Laetitia Languille, Carlos Rodiguez-Gallego, Bertrand Boisson, Sébastien Gallien, Bénédicte Neven, Marc Michel, Bertrand Godeau, Laurent Abel, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Stuart G. Tangye, Jean-Laurent Casanova, Matthieu Mahévas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], 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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Henri Mondor [Créteil], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Saclay, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP. Nord - Université Paris Cité, Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université libre de Bruxelles (ULB), Hôpital Robert Debré, Centre Hospitalier le Vinatier [Bron], Hospital Universitario Infanta Leonor [Madrid], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Sydney Children's hospital, University of New South Wales [Sydney] (UNSW), Children’s Health Queensland [Brisbane] (CHQ), CHU Necker - Enfants Malades [AP-HP], Universidad Fernando Pessoa Canarias [Las Palmas de Gran Canaria, Spain], Garvan Institute of medical research, Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Funder(s): Agence Nationale de la Recherche Award Id(s): ANR-21-RHUS-0008, ANR-10-IAHU-01, ANR-10-LABX-62-IBEID , ANR-20-CE93-003Funder(s): Fondation pour la Recherche MédicaleAward Id(s): MEMO-COV-2-FRMFunder(s): Institut PasteurFunder(s): Agence Nationale de Recherches sur le Sida et les Hépatites ViralesFunder(s): Howard Hughes Medical InstituteFunder(s): Rockefeller UniversityFunder(s): St. Giles FoundationFunder(s): National Institutes of Health Award Id(s): R01AI088364, R01AI163029, UL1TR001866Funder(s): National Center for Advancing Translational SciencesFunder(s): Fisher Center for Alzheimer’s Research FoundationFunder(s): Meyer FoundationFunder(s): JPB FoundationFunder(s): French Foundation for Medical Research Award Id(s): EQU201903007798, EA20170638020Funder(s): European Union’s Horizon 2020 Award Id(s): 824110Funder(s): Square FoundationFunder(s): Fondation du SouffleFunder(s): French Ministry of Higher Education, Research, and Innovation Award Id(s): MESRI-COVID-19Funder(s): Institut National de la Santé et de la Recherche MédicaleFunder(s): Fondation Bettencourt SchuellerFunder(s): CSL BehringFunder(s): KU Leuven Award Id(s): C16/18/007Funder(s): http://dx.doi.org/10.13039/501100003130 Award Id(s): G0C8517N, G0B5120N, G0E8420NFunder(s): Jeffrey Modell FoundationFunder(s): National Health and Medical Research Council Award Id(s): 1176665Funder(s): Allergy and Immunology Foundation of AustraliaFunder(s): John Brown Cook FoundationFunder(s): Fondation Princesse GraceFunder(s): Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherchesFunder(s): Assistance Publique—Hôpitaux de Paris Award Id(s): MEMO-COV-2Funder(s): Société Nationale de Médecine InterneFunder(s): ANRS Nord-Sud Award Id(s): ANRS-COV05Funder(s): ANR-RHU Award Id(s): ANR-21-RHUS-08 (COVIFERON)Funder(s): HORIZON-HLTH-2021-DISEASE-04 Award Id(s): 01057100Funder(s): Grandir - Fonds de solidarité pour l’enfanceFunder(s): SCOR Corporate Foundation for ScienceFunder(s): REACTing-INSERMFunder(s): University of Paris CitéFunder(s): Imagine InstituteFunder(s): VIB GC PIDFunder(s): European Research Council Award Id(s): ERC-StG MORE2ADA2, ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CHU Henri Mondor
Subjects: EXPRESSION, COVID-19 Vaccines, Immunology, VECTOR, Research & Experimental Medicine, Antibodies, Viral, DISEASE, Immunology and Allergy, Humans, PSEUDOURIDINE, Autoantibodies, B-Lymphocytes, Science & Technology, SARS-CoV-2, Vaccination, COVID-19, Antibodies, Neutralizing, Medicine, Research & Experimental, Toll-Like Receptor 7, ANTIBODIES, Spike Glycoprotein, Coronavirus, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, mRNA Vaccines, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Life Sciences & Biomedicine
Abstract: Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:220 issue:1 ispartof: location:United States status: published
Published: 2023
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7. Analysis of mRNA vaccination-elicited RBD-specific memory B cells reveals strong but incomplete immune escape of the SARS-CoV-2 Omicron variant

Author: Aurélien Sokal, Matteo Broketa, Giovanna Barba-Spaeth, Annalisa Meola, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, Matthieu Mahévas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), Hôpital Henri Mondor, Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris]-Université Paris Cité (UPCité), This work was initiated by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR and MEMO-COV-2-FRM) and funded by the Fondation Princesse Grace, an ERC Advanced Investigator Grant (B-response), and a grant from the French Ministry of Health (Soutien Exceptionnel à la Recherche Clinique 2022, CAPNET [Comité ad-hoc de pilotage national des essais thérapeutiques et autres recherches]). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. Work in the Unit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur. A.S. was supported by a Poste d’accueil from INSERM, I.F. by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), M.B. by a CIFRE fellowship from the Association Nationale de la Recherche et de la Technologie (ANRT), and A.D.L.S by a SNFMI fellowship. P.B. acknowledges funding from the French National Research Agency grant ANR-14-CE16-0011 project DROPmAbs, the Institut Carnot Pasteur Microbes et Santé (ANR 11 CARN 0017-01), the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM)., We thank Garnett Kelsoe for providing the human cell culture system, together with invaluable advice, A. Boucharlat and the Chemogenomic and Biological Screening Core Facility headed by F. Agou, as well as P. England and the Molecular Biophysics Core Facility at the Institut Pasteur, Paris, France for their support during the course of this work, Sébastien Storck, Lucie Da Silva, and Sandra Weller for their advice and support, the physicians, Constance Guillaud, Raphael Lepeule, Frédéric Schlemmer, Elena Fois, Henri Guillet, Nicolas De Prost, and Pascal Lim, whose patients were included in this study, and Florence Guivel-Benhassine and Olivier Schwartz from the Institut Pasteur for providing authentic SARS-CoV-2 B.1.1.529 virus., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: B cells, MBC, variants, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Omicron, SARS-CoV-2, VOC, Immunology, Vaccination, COVID-19, Antibodies, Viral, Antibodies, Neutralizing, Infectious Diseases, mRNA vaccine, germinal center, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, memory B cells, Immunology and Allergy, Humans, affinity, RNA, Messenger, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract: International audience; The SARS-CoV-2 Omicron variant can escape neutralization by vaccine-elicited and convalescent antibodies. Memory B cells (MBCs) represent another layer of protection against SARS-CoV-2, as they persist after infection and vaccination and improve their affinity. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant remains unclear. We assessed the affinity and neutralization potency against the Omicron variant of several hundred naturally expressed MBC-derived monoclonal IgG antibodies from vaccinated COVID-19-recovered and -naive individuals. Compared with other variants of concern, Omicron evaded recognition by a larger proportion of MBC-derived antibodies, with only 30% retaining high affinity against the Omicron RBD, and the reduction in neutralization potency was even more pronounced. Nonetheless, neutralizing MBC clones could be found in all the analyzed individuals. Therefore, despite the strong immune escape potential of the Omicron variant, these results suggest that the MBC repertoire generated by mRNA vaccines still provides some protection against the Omicron variant in vaccinated individuals.
Published: 2022
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8. Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells

Author: Aurélien Sokal, Matteo Broketa, Annalisa Meola, Giovanna Barba-Spaeth, Ignacio Fernández, Slim Fourati, Imane Azzaoui, Andrea de La Selle, Alexis Vandenberghe, Anais Roeser, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Noizat-Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Simon Fillatreau, Etienne Simon-Lorière, Jean-Claude Weill, Claude-Agnès Reynaud, Félix A. Rey, Pierre Bruhns, Pascal Chappert, and Matthieu Mahévas
Abstract: SummaryMemory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.
Published: 2021
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9. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants

Author: Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa, Imane Azzaoui, Andréa de La Selle, Alexis Vandenberghe, Slim Fourati, Anais Roeser, Annalisa Meola, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Pirenne, Jérôme Mégret, Jean-Michel Pawlotsky, Simon Fillatreau, Pierre Bruhns, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Pascal Chappert, Matthieu Mahévas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), 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), Service de bactériologie, virologie, hygiène [Mondor], Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Etablissement Français du Sang, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Inovarion, This work was initiated by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2 -FRM) and funded by the Fondation Princesse Grace and by an ERC Advanced Investigator Grant (B-response). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. Work in the Unit of Structural Virology was funded by the Institut Pasteur Urgence COVID-19 Fundraising Campaign. A.S. was supported by a Poste d’Accueil from the Institut National de la Santé et de la Recherche Médicale (INSERM), I.F. by a fellowship from the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), M.B. by a CIFRE fellowship from the Association Nationale de la Recherche et de la Technologie (ANRT), and A.d.L.S by a SNFMI fellowship. P.B. acknowledges funding from ANR (ANR-14-CE16-0011–DROPmAbs), the Institut Carnot Pasteur Microbes et Santé (ANR 11 CARN 0017-01), the Institut Pasteur, and INSERM., We thank Garnett Kelsoe for providing the human cell culture system and invaluable advice. We thank A. Boucharlat and the Chemogenomic and Biological screening core facility headed by F. Agou as well as P. England and the Molecular Biophysics core facility at the Institut Pasteur, Paris, France for support during the course of this work. We also thank Sébastien Storck, Lucie Da Silva, and Sandra Weller for advices and support and the physicians, Constance Guillaud, Raphael Lepeule, Frédéric Schlemmer, Elena Fois, Henri Guillet, Nicolas De Prost, and Pascal Lim, whose patients were included in this study., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Immunology, Antibody Affinity, Immunization, Secondary, Somatic hypermutation, Antibodies, Viral, Mass Vaccination, Article, plasma cells, RBD, Affinity maturation, 03 medical and health sciences, 0302 clinical medicine, Memory B Cells, Animals, Humans, Immunology and Allergy, Potency, B-cell memory, RNA, Messenger, Neutralizing antibody, Memory B cell, BNT162 Vaccine, Cells, Cultured, 030304 developmental biology, affinity maturation, 0303 health sciences, BNT162b2 vaccine, biology, SARS-CoV-2, Precursor Cells, B-Lymphoid, Germinal center, COVID-19, neutralizing antibody, Convalescence, Antibodies, Neutralizing, 3. Good health, somatic hypermutation, Vaccination, Infectious Diseases, germinal center, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: In addition to serum immunoglobulins, memory B cell (MBC) generation against SARS-CoV-2 represents another layer of immune protection, but the quality of MBC responses in naive and COVID-19-recovered individuals after vaccination remains ill-defined. We studied longitudinal cohorts of naive individuals and disease-recovered patients for up to 2 months after SARS-CoV-2 mRNA vaccination. We assessed the quality of the memory response by analysis of VDJ repertoires, affinity and neutralization against variants of concern (VOCs), using unbiased cultures of 2452 MBCs. Upon boosting, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOCs. Although naïve individuals had weaker neutralizing serum responses, half of their RBD-specific MBCs displayed high affinity towards multiple VOCs, including delta (B.1.617.2), and one-third retained neutralizing potency against beta (B.1.351). Our data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs., Graphical Abstract, To better understand B cell responses to SARS-CoV-2 mRNA vaccination, Sokal et al. analyzed memory B cells from COVID-19-recovered and -naive individuals. In recovered patients, vaccination amplifies a broad repertoire of matured MBCs and generates variant-neutralizing plasma cells. In naïve individuals, vaccination induces an MBC pool containing potent neutralizing clones against all current variants of concern, including beta and delta.
Published: 2021
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10. Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals

Author: Noizat-Pirenne F, Annalisa Meola, Claude-Agnès Reynaud, Magali Bouvier-Alias, Laetitia Languille, M. Broketa, Aurélien Sokal, Simon Fillatreau, Jérôme Mégret, Matthieu Mahévas, Anaïs Roeser, Jean-Claude Weill, Alexis Vandenberghe, Bertrand Godeau, Marc Michel, Giovanna Melica, Pascal Chappert, Slim Fourati, Zarrouk, Félix A. Rey, Etienne Crickx, Giovanna Barba-Spaeth, S. Gallien, Imane Azzaoui, Yann Nguyen, Florence Canoui-Poitrine, La Selle Ad, Bruhns P, Jean-Michel Pawlotsky, and Ignacio Fernandez
Subjects: Vaccination, Messenger RNA, Coronavirus disease 2019 (COVID-19), Repertoire, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Potency, Biology, Memory B cell, Neutralization
Abstract: SummaryHow a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.
Published: 2021
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11. Factors associated with the emergence of integrase resistance mutations in patients failing dual or triple integrase inhibitor-based regimens in a French national survey

Author: Anne-Genevieve, Marcelin, Charlotte, Charpentier, Pantxika, Bellecave, Basma, Abdi, Marie-Laure, Chaix, Virginie, Ferre, Stephanie, Raymond, Djeneba, Fofana, Laurence, Bocket, Audrey, Mirand, Helene, Le Guillou-Guillemette, Brigitte, Montes, Corinne, Amiel, Coralie, Pallier, Samira, Fafi-Kremer, Anne, De Monte, Elodie, Alessandri-Gradt, Caroline, Scholtes, Anne, Maillard, Helene, Jeulin, Magali, Bouvier-Alias, Catherine, Roussel, Georges, Dos Santos, Anne, Signori-Schmuck, Julia, Dina, Sophie, Vallet, Karl, Stefic, Cathia, Soulié, Vincent, Calvez, Diane, Descamps, Philippe, Flandre, S, Marque Juillet, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, CHU Strasbourg, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Rouen, Normandie Université (NU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Amiens-Picardie, CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Caen Normandie (UNICAEN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de virologie et unité de surveillance biologique [Bordeaux], Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, genotype, Integrase inhibitor, hiv, HIV Infections, gerstmann-straussler-scheinker, HIV Integrase, viral load result, chemistry.chemical_compound, 0302 clinical medicine, Genotype, Pharmacology (medical), 030212 general & internal medicine, Univariate analysis, biology, 3. Good health, Integrase, univariate analysis, integrase inhibitors, Infectious Diseases, Tolerability, Dolutegravir, Heterocyclic Compounds, 3-Ring, medicine.drug, Microbiology (medical), medicine.medical_specialty, Pyridones, 030106 microbiology, 03 medical and health sciences, Internal medicine, Raltegravir Potassium, Drug Resistance, Viral, medicine, Humans, HIV Integrase Inhibitors, plasma, Pharmacology, disease, business.industry, genetics raltegravir dolutegravir, Raltegravir, Regimen, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Mutation, biology.protein, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, hiv-1 integrase, business
Abstract: Background Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance. Materials and methods A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens [two consecutive plasma viral load (VL) values >50 copies/mL] was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm. Results Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0–0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model. Conclusions This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.
Published: 2021
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12. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author: Mickaël M. Ménager, Marine Luka, Marc Michel, Sophie Hue, Slim Fourati, Aurélien Sokal, Simon Fillatreau, Claude-Agnès Reynaud, Giovanna Barba-Spaeth, Annalisa Meola, Laetitia Languille, Jean-Michel Pawlotsky, Matthieu Mahévas, Jérôme Mégret, Félix A. Rey, Etienne Crickx, Asma Beldi-Ferchiou, Magali Bouvier-Alias, Jean-Claude Weill, Imane Azzaoui, Alexis Vandenberghe, Pascal Chappert, Samia Baloul, Anaïs Roeser, Ignacio Fernandez, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Inovarion, Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie, virologie, hygiène [Mondor], Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), 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)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Vaccine Research Institute (VRI), Physiopathologie et immunothérapies dans l’infection VIH [Créteil] (Inserm U955 Équipe 16), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), This work was supported by a grant from the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale (ANR, MEMO-COV-2), by the Fondation Princesse Grace, and, in part by an ERC Advanced Investigator Grant (B-response). Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Clinique et du Développement) was the promotor and the sponsor of MEMO-COV-2. A.S. was supported by a Poste d’Accueil from Inserm, A.R. by an Année Recherche from AP-HP and by a SNFMI fellowship., ANR-20-COVI-0072,MEMO-COV-2,Lymphocytes B et T CD4 mémoires spécifiques du virus chez les patients guéris du Covid-19(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute [Créteil, France] (VRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Adult, Somatic cell, Cell, Somatic hypermutation, Context (language use), Biology, Lymphocyte Activation, spike protein, Severity of Illness Index, Article, General Biochemistry, Genetics and Molecular Biology, plasma cells, RBD, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, medicine, Humans, neutralizing antibodies, Memory B cell, B cell, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, Germinal center, COVID-19, OC43, Middle Aged, Flow Cytometry, 3. Good health, somatic hypermutation, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, germinal center, Spike Glycoprotein, Coronavirus, Immunology, extrafollicular response, Single-Cell Analysis, HKU1, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection., Graphical abstract, The B cell response against SARS-CoV-2 shows a temporal shift from an extrafollicular reaction that includes memory B cells against seasonal coronaviruses toward a germinal center-dependent memory response encoding (spike-specific) neutralizing antibodies.
Published: 2021
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13. Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Author: Aurélien Sokal, Pascal Chappert, Anais Roeser, Giovanna Barba-Spaeth, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Ignacio Fernandez, Magali Bouvier-Alias, Etienne Crickx, Asma Beldi Ferchiou, Sophie Hue, Laetitia Languille, Samia Baloul, France Noizat-Pirenne, Marine Luka, Jérôme Megret, Mickaël Ménager, Jean-Michel Pawlotsky, Simon Fillatreau, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, and Matthieu Mahévas
Subjects: medicine.anatomical_structure, Somatic cell, Repertoire, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Cell, Immunology, medicine, Germinal center, Biology, Memory B cell, Gene, B cell
Abstract: Memory B cells play a fundamental role in host defenses against viruses, but to date, their role have been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 Spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including preexisting cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late remarkably stable memory B-cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.
Published: 2020
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14. Performance of a high-throughput, automated enzyme immunoassay for the detection of SARS-CoV-2 antigen, including in viral 'variants of concern': Implications for clinical use

Author: Aurélie Gourgeon, Dominique Challine, Arnaud Galbin, Alexandre Soulier, Amélie Dublineau, Anne Le Bouter, Camille Langlois, Souraya Khouider, Magali Bouvier-Alias, Slim Fourati, Marie Joanny, Stéphane Chevaliez, Jean-Michel Pawlotsky, Etienne Audureau, and Christophe Rodriguez
Subjects: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS CoV-2, Antigen test, Nucleic Acid Testing, Sensitivity and Specificity, Article, EIA, Immunoenzyme Techniques, Sensitivity, Antigen, Virology, Antigen assays, Medicine, Humans, In patient, Antigens, Viral, Retrospective Studies, chemistry.chemical_classification, Variants of concern, Immunoassay, medicine.diagnostic_test, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, Infectious Diseases, Enzyme, chemistry, Specificity, RNA, Viral, business
Abstract: Direct detection of SARS-CoV-2 viral antigens could replace RT-PCR, provided that its clinical performance is validated in different epidemiological settings. Here, we evaluated the performance of the VITROS Antigen test, an enzyme immunoassay detecting a SARS-CoV-2 antigen, in NPSs from 3 cohorts of patients. Methods . Three cohorts including SARS-CoV-2 RNA-positive samples collected during the first and second wave of the French epidemic between March 2020 and February 2021 (including variant B.1.1.7/α and variant B.1.351/β). Results . Among the 1763 prospectively tested subjects, 8.2% (145/1763) were SARS-CoV-2 RNA-positive by RT-PCR. Using Ct ≤30 and Ct ≤35 as thresholds, the sensitivities of the antigen assay were 98.8% (93.6-100%) and 93.5% (87.0-97.3%), respectively. The overall specificity of the assay was 100% (1614/1614; 99.8-100%). In a retrospective cohort of subjects infected with variants of concern, 90.4% (47/52) of NPSs containing B. B.1.1.7/α (Ct ≤35) and 100% (7/7) of those containing B.1.351/β were positive with the VITROS EIA SARS-CoV-2 Antigen test. Conclusion . The excellent performance of the EIA Antigen test reported here, including in patients infected with viral “variants of concern”, support the use of high-throughput, EIA-based SARS-CoV-2 antigen assays as an alternative or complement to nucleic acid testing in order to scale-up laboratory screening and diagnostic capacities.
Published: 2021

15. La diversité du répertoire des cellules B mémoires fait face aux variants du SRAS-CoV2 après la vaccination par ARNm chez les individus naïfs et guéris

Author: Pascal Chappert, Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernandez, Matteo Broketta, Imane Azzaoui, Andrea De La Selle, Alexis Vandenberghe, Slim Fourati, Annalisa Meola, Magali Bouvier-Alias, Etienne Cricks, Laetitia Languille, Marc Michel, Bertrand Godeau, Florence Canoui-Poitrine, France Pirenne, Jérôme Megret, Jean-Michel Pawlotsky, Pierre Bruhns, Felix Rey, Jean-Claude Weill, Claude-Agnès Reynaud, and Matthieu Mahévas
Subjects: Biochemistry (medical), Clinical Biochemistry, Hematology
Published: 2021
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16. 25‐OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV‐infected patients

Author: Arthur Belle, Emmanuel Gizard, Laurent Peyrin-Biroulet, Jean-Pierre Bronowicki, Jean-Michel Pawlotsky, Magali Bouvier-Alias, Anthony Lopez, Stéphanie Rouanet, and Guillaume Conroy
Subjects: 0301 basic medicine, medicine.medical_specialty, Hepatitis C virus, medicine.disease_cause, Gastroenterology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Fibrosis, law, Internal medicine, Genotype, medicine, Vitamin D and neurology, business.industry, Ribavirin, Original Articles, Hepatitis C, medicine.disease, 030104 developmental biology, Oncology, chemistry, Population study, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND AND AIM The impact of 25-OH vitamin D on sustained viral response (SVR) to antiviral therapy and on fibrosis progression in hepatitis C is debated. We assessed the impact of 25-OH vitamin D concentration on the efficacy of antiviral therapy in naive genotype 1 hepatitis C virus (HCV)-infected patients. METHODS The study population consisted of treatment-naive genotype 1 patients enrolled in a randomised controlled trial. A total of 516 patients received peginterferon α-2a 180 µg/week plus ribavirin 800 mg/day for 24 weeks. There were 349 patients with undetectable HCV RNA (
Published: 2017
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17. New HIV-1 circulating recombinant form 94: from phylogenetic detection of a large transmission cluster to prevention in the age of geosocial-networking apps in France, 2013 to 2017

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

Author: Vincent Thibault, Benjamin Nemoz, Magali Bouvier-Alias, P. Marcellin, Françoise Lunel-Fabiani, Vincent Leroy, C. Henquell, Etienne Brochot, Patrice Morand, T. Semenova, Christopher Payan, Gilles Duverlie, S. Vallet, Pascale Trimoulet, Sylvie Larrat, L. Izquierdo, Gisèle Lagathu, A. M. Roque-Afonso, Sarah Maylin, Stéphane Chevaliez, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pontchaillou [Rennes], Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), 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), 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 [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), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université Grenoble Alpes (UGA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Institut de biologie structurale (IBS - UMR 5075), 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)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Databases, Factual, Epidemiology, Hepacivirus, medicine.disease_cause, Severity of Illness Index, Tertiary Care Centers, 0302 clinical medicine, Genotype, Prevalence, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDE.IE]Environmental Sciences/Environmental Engineering, Incidence (epidemiology), Hepatitis C, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, 030211 gastroenterology & hepatology, Female, France, Viral hepatitis, Adult, treatment-naive HCV, medicine.medical_specialty, Hepatitis C virus, [SDE.MCG]Environmental Sciences/Global Changes, Population, HCV genotypes, Statistics, Nonparametric, 03 medical and health sciences, Viral Proteins, Internal medicine, medicine, Humans, education, Retrospective Studies, Hepatitis, Original Paper, business.industry, fibrosis, Hepatitis C, Chronic, medicine.disease, [SDE.ES]Environmental Sciences/Environmental and Society, 030104 developmental biology, Logistic Models, Multivariate Analysis, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business
Abstract: Treatment options for Hepatitis C infection have greatly improved with direct-acting antiviral (DAA) combinations achieving high cure rates. Nevertheless, the cost of this treatment is still high and access to treatment in many countries has been preferentially reserved for patients with more severe fibrosis (F3 and F4). In this French nationwide study, we investigated the epidemiological characteristics and genotype distribution of hepatitis C virus (HCV) in treatment-naive patients with METAVIR fibrosis stages between F0 and F2 in order to identify patient profiles that became eligible for unrestricted treatment in a second period. Between 2015 and 2016 we collected data from nine French university hospitals on a total of 584 HCV positive patients with absent, mild or moderate liver fibrosis. The most represented genotypes were genotype 1b (159/584; 27.2%), followed by genotype 1a (150/584; 25.7%); genotype 3 (87/584: 14.9%); genotype 4 (80/584; 13.7%). Among genotype 4: 4a was predominantly encountered with 22 patients (27.5% of genotype 4). Genotypes 1b and 1a are currently the most frequent virus types present in treatment-naive patients with mild fibrosis in France. They can be readily cured using the available DAA. Nevertheless, non-a/non-d genotype 4 is also frequent in this population and clinical data on the efficacy of DAA on these subtypes is missing. The GEMHEP is the French group for study and evaluation of viral hepatitis on a national scale. Data collection on epidemiological and molecular aspects of viral hepatitis is performed on a regular basis in all main French teaching hospitals and serves as a basis for surveillance of these infections. Analysis and trends are regularly published on behalf of the GEMHEP group. Data collection was performed retrospectively over the 2015–2016 period, covering nine main university hospitals in France. A total of 584 hepatitis C positive patients were included in this study. Genotyping of the circulating viruses showed a high prevalence of genotypes 1b and 1a in our population. The epidemiology of hepatitis C is slowly changing in France, particularly as a consequence of the rise of ‘non-a non-d’ genotype 4 viruses mainly originating from African populations. More data concerning treatment efficacy of these genotypes is needed in order to guide clinical care.
Published: 2019
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19. Multicenter clinical evaluation of the new 3rd generation assay for detection of antibodies against hepatitis C virus on the VIDAS® system

Author: V. Barlet, José M. Echevarría, Michael Hausmann, Ana Avellón, R. Croise, W. Abdelhady, F. Descamps, Jean-Marc Dugua, Magali Bouvier-Alias, M. Rafik, B. Seignères, Stéphane Chevaliez, and Jean-Michel Pawlotsky
Subjects: 0301 basic medicine, Hepatitis C virus, Hepacivirus, 030204 cardiovascular system & hematology, medicine.disease_cause, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Immune system, Virology, Genotype, Animals, Humans, Medicine, Serologic Tests, Organ donation, Seroconversion, Immunoassay, biology, business.industry, virus diseases, Hepatitis C Antibodies, medicine.disease, Hepatitis C, digestive system diseases, 030104 developmental biology, Infectious Diseases, Spain, Immunology, biology.protein, Egypt, France, Antibody, business, Viral hepatitis, Clinical evaluation
Abstract: Background Detection of antibodies (anti-HCV) against hepatitis C virus (HCV) is indispensable for screening and diagnosis of viral hepatitis and for the viral safety of blood, tissue or organ donations. It gains additional importance by the new HCV drugs which improve the therapeutic possibilities dramatically. Objective To evaluate the performance of a newly developed immune assay for anti-HCV based on the well-established VIDAS platform. Study design The assay was evaluated with samples from anti-HCV negative blood donors and from patients with or without HCV markers in six centres in France, Spain and Egypt. The status of the samples was determined by using CE-marked immune assays (Architect, AxSym, Prism, Vitros), two immunoblots (RIBA, Inno-Lia) and/or HCV RNA results. Results Specificity was 99.67% in 10,320 French blood donors without anti-HCV, 99.5% in 200 anti-HCV negative hospitalized European patients and 99.0% in 198 negative patients from Egypt. Sensitivity was 99.7% in 1054 patients pretested positive by other assays; 345 patients with known genotype had genotype 1–6; 61 patients were co-infected with HIV. VIDAS was reactive in 78% of 91 patients with uncertain or very weak anti-HCV. It became on average positive at day 37 with seroconversion panels. Conclusions This multicentric, international study with >12,000 samples show that the new VIDAS anti-HCV assay is very suitable for screening and confirmation of HCV infection. Sensitivity, specificity and recognition of seroconversion compare favorably with well-established CE-marked tests and help to clarify discrepant results obtained with other assays.
Published: 2016
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20. Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir‐containing regimen

Author: Magali Bouvier-Alias, Ariane Mallat, Isaac Ruiz, Françoise Roudot-Thoraval, Alexandre Soulier, Stéphane Chevaliez, Jean-Michel Pawlotsky, Giovanna Scoazec, Anne Varaut, Cyrille Feray, and Christophe Hézode
Subjects: Male, 0301 basic medicine, Simeprevir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, Hepatitis C virus, Pilot Projects, medicine.disease_cause, Antiviral Agents, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, Internal medicine, medicine, Humans, Treatment Failure, NS5A, Hepatology, business.industry, Ribavirin, Imidazoles, Valine, Hepatitis C, Chronic, Middle Aged, Surgery, 030104 developmental biology, chemistry, Asunaprevir, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Carbamates, business, medicine.drug
Abstract: UNLABELLED Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated variants (RAVs). To avoid cross-resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This "real-world" study comprised patients who had failed to achieve SVR on previous NS5A-based therapy with daclatasvir (DCV) plus pegylated interferon (Peg-IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post-treatment); on-treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43-73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6-70 kPa; cirrhosis, n = 9); median baseline HCV-RNA level was 1.38 × 10(6) IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (
Published: 2016
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21. Multicenter clinical comparative evaluation of Alinity m HIV-1 assay performance

Author: Natalia Marlowe, Jens Dhein, Monia Pacenti, Ajith M. Joseph, Alba Vilas, Gudrun Naeth, Laura Martínez-García, Rory N. Gunson, Martin Obermeier, Jodie D’costa, Maria Krügel, Patrick Braun, Michael J. Palm, Danijela Lucic, Rizmina Sameer, Karin Pfeifer, Magali Bouvier-Alias, Juan Carlos Galán, Francesco Onelia, Emily Goldstein, Allison Glass, Robert Ehret, Leana Maree, Heribert Knechten, and Birgit Reinhardt
Subjects: RealTime HIV-1, 0301 basic medicine, Dual target, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Diagnostic accuracy, Biology, Alinity m HIV-1, medicine.disease_cause, Sensitivity and Specificity, Rapid detection, Comparative evaluation, 03 medical and health sciences, 0302 clinical medicine, Virology, Viral load monitoring, medicine, Humans, HIV-1 RNA, Hologic Aptima HIV-1, 030212 general & internal medicine, Clinical decision, Reproducibility, Chromatography, Reproducibility of Results, virus diseases, Viral Load, Infectious Diseases, HIV-1, Dual probe, RNA, Viral, Reagent Kits, Diagnostic
Abstract: Background Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection. Objective We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform. Study design This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories. Alinity m HIV-1 assay precision, detectability, and reproducibility was compared across four study sites. Results The Alinity m HIV-1 assay produced comparable results to currently available HIV-1 assays (correlation coefficient >0.995), with an overall bias of -0.1 to 0.10 Log10 copies/mL. The Alinity m HIV-1 assay and its predecessor m2000 HIV-1 assay demonstrated comparable detection of 16 different HIV-1 subtypes (R2 = 0.956). A high level of agreement (>88 %) between all HIV-1 assays was seen near clinical decision points of 1.7 Log10 copies/mL (50 copies/mL) and 2.0 Log10 copies/mL (200 copies/mL). Alinity m HIV-1 assay precision was 0.08 and 0.21 Log10 copies/mL at VLs of 1000 and 50 copies/mL, respectively, with a high level of detectability (≥97 % hit rate) and reproducibility across sites. Conclusions The Alinity m HIV-1 assay provides comparable diagnostic accuracy to current HIV-1 assays, and when run on the Alinity m system, has the capacity to shorten the time between diagnosis and treatment.
Published: 2020
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22. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France

Author: Gilles Peytavin, Mary-Anne Trabaud, Anne Signori-Schmuck, Charlotte Charpentier, Marc Wirden, Cécile Henquell, Laurence Bocket, Catherine Delamare, Samira Fafi-Kremer, Jacques Izopet, Chakib Allaoui, Georges Dos Santos, A. Beby-Defaux, Benoit Visseaux, Virginie Ferré, Coralie Pallier, Diane Descamps, Stéphanie Marque-Juillet, Lambert Assoumou, Magali Bouvier-Alias, Sophie Vallet, Alexis de Rougemont, Hélène Le Guillou-Guillemette, Vincent Calvez, Stéphanie Raymond, Corinne Amiel, Honorine Fenaux, Anne De Monte, Francis Barin, Anne Krivine, Véronique Avettand-Fenoel, Annick Allardet-Servent, Jean-Christophe Plantier, Rachid Ait-Namane, Laurence Morand-Joubert, Marie-Laure Chaix, Camille Tumiotto, Maxime Grude, Anne Maillard, Laurence Courdavault, Brigitte Montes, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital Avicenne [AP-HP], CHU Clermont-Ferrand, Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de la Martinique [Fort de France], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Victor Dupouy, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Mzembaba, Sandy, Epidémiologie, Systèmes d'Information, Modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Laboratoire de Virologie-Immunologie [Fort de France, Martinique] (EA 4537), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Argenteuil (CH Argenteuil), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Paris Descartes, Sorbonne Paris Cité, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and ANRS – France REcherche Nord&Sud Sida-hiv Hépatites
Subjects: 0301 basic medicine, Male, MESH: CD4 Lymphocyte Count, [SDV]Life Sciences [q-bio], Integrase inhibitor, hiv, HIV Infections, Drug resistance, MESH: HIV-1 / genetics, MESH: Genotype, MESH: HIV Infections / epidemiology, 0302 clinical medicine, Genotype, Blood plasma, HIV Seropositivity, rna-directed dna polymerase, Prevalence, rna, Pharmacology (medical), 030212 general & internal medicine, MESH: Chronic Disease / epidemiology, ComputingMilieux_MISCELLANEOUS, cd4 count determination procedure, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, anti-retroviral agents, MESH: France / epidemiology, Antiinfective agent, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Drug Resistance, Viral / genetics, 3. Good health, endopeptidases, [SDV] Life Sciences [q-bio], integrase inhibitors, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: RNA, Viral / blood, Female, France, MESH: HIV Seropositivity / epidemiology, Microbiology (medical), Adult, medicine.medical_specialty, peptide hydrolases, MESH: Mutation, Anti-HIV Agents, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: HIV-1 / classification, MESH: HIV-1 / drug effects, Virus, MESH: HIV Infections / transmission, 03 medical and health sciences, Pharmacotherapy, Internal medicine, Drug Resistance, Viral, medicine, Humans, viruses, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, plasma, safe sex, MESH: Prevalence, Pharmacology, drug resistance, MESH: Humans, business.industry, MESH: Adult, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, CD4 Lymphocyte Count, MESH: Anti-HIV Agents / therapeutic use, Chronic Disease, Mutation, HIV-1, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages.
Published: 2018
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23. Detection of numerous HIV-1/MO recombinants in France

Author: Elyanne Gault, Fabienne De Oliveira, Véronique Lemée, Jean-Christophe Plantier, Véronique Schneider, Alice Moisan, Thomas Mourez, Marie-Laure Chaix, Marc Wirden, Laurence Bocket, Jean-Dominique Poveda, Magali Bouvier-Alias, Charlotte Pronier, Pierre Cappy, Elodie Alessandri-Gradt, Odile Morvan, 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], 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, Service de virologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Virologie CHU Henri Mondor, Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Microbiologie et Hygiène [AP-HP Hôpital Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Laboratoire de Biologie Médicale CH Saint Brieuc, Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Service de virologie [Hôpital Tenon], CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], Service de Virologie [Lille], Hôpital Henri Mondor, Université Paris Diderot - Paris 7 (UPD7)-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 hospitalier Saint-Brieuc, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and AP-HP Hôpital Ambroise-Paré [Boulogne-Billancourt]
Subjects: Adult, Male, 0301 basic medicine, Serotype, Genotyping Techniques, Sequence analysis, 030106 microbiology, Immunology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, law.invention, Serology, Evolution, Molecular, 03 medical and health sciences, law, Genetic variation, medicine, Humans, Immunology and Allergy, Serotyping, ComputingMilieux_MISCELLANEOUS, Recombination, Genetic, business.industry, Genetic Variation, Sequence Analysis, DNA, Middle Aged, Viral Load, Virology, 3. Good health, Genetic divergence, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Recombinant DNA, Female, France, business, Viral load
Abstract: BACKGROUND The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species. METHODS The French National Reference Centre for HIV received samples within the framework of mandatory notification of HIV infections, and for expert analysis. A strategy combining serotyping, viral quantification, group-specific molecular amplification and whole-genome sequencing was used for strain characterization and complementary investigations. RESULTS We identified one patient with M+O infection, three patients with M+O infection associated with an MO recombinant, and six patients with only an MO recombinant. These atypical infections were detected upon strain characterization (n = 4) or because of anomalies during patient monitoring (n = 6). We identified eight new URF_MO, all but one originating from Cameroon. Interestingly, two distinct recombinant strains were found in two unrelated patients, representing possible precursors of a CRF_MO. CONCLUSION Our work highlights the fact that the continuous evolution of HIV can hinder diagnosis and complicate clinical practice. We stress that unexpected results during diagnosis or monitoring necessitate further serological and molecular exploration, these atypical infections influence biological and therapeutic management and necessitate appropriate tools, and specific surveillance is necessary, especially as the frequency of such infections may be underestimated.
Published: 2018
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24. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial

Author: Fabien Zoulim, Jean-Michel Molina, Laurent Alric, Isabelle Rosa, Magali Picon, Magali Bouvier-Alias, Pascaline Rabiega, Pierre Attali, Yannick Bacq, Patrizia Carrieri, Dominique Thabut, Marc Bourlière, Albert Tran, Vincent Leroy, Inga Bertucci, Fabrice Carrat, Christophe Hézode, Jean-Pierre Bronowicki, Dominique Guyader, Jean-Didier Grangé, Yoann Barthe, Nathalie Ganne-Carrié, Patrick Marcellin, Xavier Causse, Ghassan Riachi, Lawrence Serfaty, Hélène Fontaine, Hôpital Saint-Joseph [Marseille], 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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service d'hépato-gastro-entérologie [APHP 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 Hospitalier du Pays d'Aix, Centre Hospitalier Régional d'Orléans (CHRO), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Hôpital Charles Nicolle [Rouen], CHI Créteil, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), ANRS France Recherche Nord & sud Sida-hiv hépatites, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Paul Brousse, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service d'hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, Male, Serum, HBsAg, analysis, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, Hepatitis, 0302 clinical medicine, Pegylated interferon, Pregnancy, Hepatitis B e Antigens, Nucleotides, Nucleosides, Hepatitis B, Middle Aged, Recombinant Proteins, 3. Good health, Intention to Treat Analysis, HBeAg, Hepatocellular carcinoma, Medicine, 030211 gastroenterology & hepatology, Female, France, medicine.drug, Adult, medicine.medical_specialty, Hepatitis B virus, Adolescent, Patients, contraindications, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antiviral Agents, Drug Administration Schedule, Time, Injections, methods, 03 medical and health sciences, Young Adult, Hepatitis B, Chronic, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, Aged, therapy, Hepatitis B Surface Antigens, Hepatology, business.industry, Carcinoma, Interferon-alpha, Dna, medicine.disease, Regimen, 030104 developmental biology, Immunology, DNA, Viral, business
Abstract: International audience; BACKGROUND: Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. METHODS: In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum alpha fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (\textless or \textgreater/=2.25 log10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 mug per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. FINDINGS: Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7.8%) of 90 patients in the pegylated interferon plus nucleos(t)ide analogues group versus three (3.2%) of 93 in the nucleos(t)ide analogues-alone group (difference 4.6% [95% CI -2.6 to 12.5]; p=0.15). 85 (94%) of 90 patients started pegylated interferon, three (4%) of whom had a dose reduction and 17 (20%) had an early discontinuation of pegylated interferon (seven [41%] for serious adverse events). Grade 3 and 4 adverse events were more frequent in the pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues-alone group (three [3%] grade 3; six [6%] grade 4). INTERPRETATION: Addition of a 48 week course of pegylated interferon to nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a least 1 year was poorly tolerated and did not result in a significant increase of HBsAg clearance. FUNDING: Institut national de la sante et de la recherche medicale-Agence nationale de recherches sur le sida et les hepatites virales (France Recherche Nord&sud Sida-vih Hepatites)
Published: 2017
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25. Pegylated interferon α-2a triggers NK-cell functionality and specific T-cell responses in patients with chronic HBV infection without HBsAg seroconversion

Author: Ophelie Brevot-Lutton, Noelle Pouget, Tania Dufeu-Duchesne, Caroline Aspord, Magali Bouvier-Alias, Joel Plumas, Marc Bourlière, Juliana Bruder Costa, Vincent Leroy, Inga Bertucci, Fabien Zoulim, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ANRS, Agence Nationale de Recherches sur le Sida et les Hepatites Virales, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: Male, T-Cell Antigen Receptor Specificity, Lymphocyte Activation, Polyethylene Glycols, Interleukin 21, 0302 clinical medicine, Animal Cells, T-Lymphocyte Subsets, phase 3 clinical trial (topic), T lymphocyte, Public and Occupational Health, IL-2 receptor, CD8+ T lymphocyte, lcsh:Science, Immune Response, Innate Immune System, clinical article, Innate lymphoid cell, Acquired immune system, 3. Good health, cell activation, Killer Cells, Natural, lymphocyte function, Interleukin 12, Cytokines, 030211 gastroenterology & hepatology, Cellular Types, phenotype, Immune Cells, T cell, Immunology, Cytotoxic T cells, Article, peginterferon alpha2a, 03 medical and health sciences, Hepatitis B, Chronic, Humans, chronic hepatitis B, T Helper Cells, human, seroconversion, Aged, CD4+ T lymphocyte, Blood Cells, Hepatitis B Surface Antigens, human cell, lcsh:R, Biology and Life Sciences, Dendritic Cells, Molecular Development, hepatitis B surface antigen, 030104 developmental biology, DNA, Viral, lcsh:Q, Preventive Medicine, Biomarkers, Developmental Biology, 0301 basic medicine, Physiology, T-Lymphocytes, lcsh:Medicine, NK cells, White Blood Cells, Liver Function Tests, Immune Physiology, Medicine and Health Sciences, randomized controlled trial (topic), innate immunity, Staining, Multidisciplinary, T Cells, Cell Staining, adaptive immunity, Middle Aged, Viral Load, Vaccination and Immunization, Recombinant Proteins, Treatment Outcome, medicine.anatomical_structure, multicenter study (topic), Female, Research Article, Adult, dendritic cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, cellular immunity, Biology, Research and Analysis Methods, Natural killer cell, Immune system, Antiviral Therapy, evolution, medicine, drug mechanism, controlled study, nucleoside analog, Interferon-alpha, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, natural killer cell, Specimen Preparation and Treatment, Immune System
Abstract: International audience; Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. © 2016 Bruder Costa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2016
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26. Erythrocyte and plasma ribavirin concentrations in the assessment of early and sustained virological responses to pegylated interferon-alpha 2a and ribavirin in patients coinfected with hepatitis C virus and HIV

Author: Caroline Solas, Christine Katlama, Isabelle Poizot-Martin, Anne-Sophie Lascaux, Magali Bouvier-Alias, Gilles Peytavin, Jade Ghosn, Stéphanie Dominguez, Yves Levy, Bruno Cassard, and Giovanna Melica
Subjects: Adult, Male, Microbiology (medical), medicine.medical_specialty, Erythrocytes, Hepatitis C virus, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Antiviral Agents, Gastroenterology, Polyethylene Glycols, Hemoglobins, Plasma, Cmin, chemistry.chemical_compound, Internal medicine, Ribavirin, medicine, Humans, Pharmacology (medical), In patient, Reduced haemoglobin, Pharmacology, medicine.diagnostic_test, business.industry, Interferon-alpha, virus diseases, Middle Aged, Viral Load, Hepatitis C, Recombinant Proteins, digestive system diseases, Treatment Outcome, Infectious Diseases, chemistry, Therapeutic drug monitoring, Pegylated interferon alpha 2a, Immunology, business
Abstract: To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions.Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C(min)).Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95% CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC 0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%; specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4 (P = 0.05).Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.
Published: 2012
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27. 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
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28. 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
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29. Daily Cannabis Use: A Novel Risk Factor of Steatosis Severity in Patients With Chronic Hepatitis C

Author: Jean–Michel Pawlostky, Ariane Mallat, Charlotte Costentin, Christophe Hézode, Elie Serge Zafrani, Fatiha Medkour, Francoise Roudot Thoraval, Ali Hessami, Magali Bouvier–Alias, and Sophie Lotersztajn
Subjects: Adult, Male, medicine.medical_specialty, Genotype, medicine.medical_treatment, Marijuana Smoking, Hepacivirus, Severity of Illness Index, Gastroenterology, Body Mass Index, Predictive Value of Tests, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Risk factor, Cannabis smoking, Hepatology, biology, business.industry, Hepatitis C, Odds ratio, Hepatitis C, Chronic, Middle Aged, Viral Load, medicine.disease, biology.organism_classification, Surgery, Fatty Liver, Logistic Models, Liver, Multivariate Analysis, RNA, Viral, Female, Cannabis, Steatosis, business, Body mass index
Abstract: Steatosis is highly prevalent in patients with chronic hepatitis C (CHC) and has been reported to increase fibrosis and reduce the rate of viral eradication. Two recent studies indicate that endocannabinoids promote experimental steatosis via activation of hepatic CB1 receptors. We therefore investigated the impact of cannabis smoking on steatosis severity during CHC.A total of 315 consecutive patients with untreated CHC undergoing liver biopsy were included. Detailed histories of recent cannabis, alcohol, and tobacco use were recorded. Steatosis, activity, and fibrosis stage were assessed by 2 pathologists according to METAVIR. Marked steatosis was defined as/=30%. Patients were categorized as cannabis nonusers (63.5%), occasional cannabis smokers (12.4%), or daily cannabis smokers (24.1%).Multivariate analysis identified 6 predictors of marked steatosis: daily cannabis use (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.01-4.5]), activity grade/=A2 (OR, 2.1; 95% CI, 1.0-4.3), genotype 3 (OR, 5.4; 95% CI, 2.6-11.3), hyperglycemia or diabetes (OR, 5.1; 95% CI, 1.8-15.0), body mass index27 kg/m(2) (OR, 2.1; 95% CI, 1.0-4.3), and serum HCV RNA load (OR, 1.7; 95% CI, 1.0-2.9). Upon adjustment of HCV genotype (3 vs non-3) or alcohol intake (30 g/day vs/=30 g/day), marked steatosis was more frequent in daily cannabis users compared with occasional users and nonusers (P = .03 and P = .008, respectively).Our results identify daily cannabis smoking as a novel independent predictor of steatosis severity during CHC and strongly argue for a steatogenic role of the cannabinoid system. Cannabis use should be discouraged in patients with CHC.
Published: 2008
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30. O112 : HBsAg clearance after addition of 48 weeks of pegifn in HBeAg negative CHB patients on nucleos(T)ide therapy with undetectable hbvdna for at least one year: final results from ANRS-HB06 pegan study: multicenter randomized controlled phase III trial

Author: Maurice Picon, Yannick Bacq, Jean-Didier Grangé, Hélène Fontaine, Pierre Attali, Christophe Hézode, Patrick Marcellin, Dominique Guyader, Inga Bertucci, Fabrice Carrat, Magali Bouvier-Alias, Vincent Leroy, Jean-Michel Molina, Lawrence Serfaty, M. Bourlière, Nathalie Ganne-Carrié, Jean-Pierre Bronowicki, A. Tran, N. Pouget, Xavier Causse, Isabelle Rosa, Yves Benhamou, Ghassan Riachi, Pascaline Rabiega, Fabien Zoulim, Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Service des maladies du foie, Centre Hospitalier Universitaire [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidémiologie, Systèmes dínformation et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Centre Hospitalier Universitaire [Rennes], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service des maladies du foie [CHU Rennes], Centre Hospitalier Universitaire [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Service d'hépatologie [CHU Saint-Antoine]
Subjects: medicine.medical_specialty, HBsAg, Hepatology, business.industry, [SDV]Life Sciences [q-bio], Gastroenterology, Virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Hbeag negative, Internal medicine, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2015
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31. Effect of Ribavirin in Genotype 1 Patients With Hepatitis C Responding to Pegylated Interferon Alfa-2a Plus Ribavirin

Author: P. Melin, Christophe Hézode, Hervé Desmorat, Jean-Pierre Bronowicki, Albert Tran, Magali Bouvier–Alias, F. Montestruc, Denis Ouzan, Michelle Chevalier, Jean-Pierre Zarski, Stéphane Chevaliez, Jean-Michel Pawlotsky, Christophe Renou, Marc Bourlière, Isabelle Lonjon–Domanec, Tarik Asselah, and Juliette Foucher
Subjects: Adult, Male, medicine.medical_specialty, Genotype, Hepatitis C virus, Hepacivirus, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, Interferon, Pegylated interferon, Internal medicine, Ribavirin, medicine, Humans, Fatigue, Hepatology, business.industry, Standard treatment, Interferon-alpha, virus diseases, Alanine Transaminase, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Recombinant Proteins, digestive system diseases, Logistic Models, Treatment Outcome, chemistry, Immunology, Quality of Life, RNA, Viral, Drug Therapy, Combination, Female, business, Viral load, Follow-Up Studies, medicine.drug, Pegylated Interferon Alfa
Abstract: Background & Aims: Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. Methods: A total of 516 patients were treated with pegylated interferon alfa-2a, 180 μg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone. Results: Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2. Conclusions: We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1–infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.
Published: 2006
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32. Interferon‐Ribavirin in Association with Stavudine Has No Impact on Plasma Human Immunodeficiency Virus (HIV) Type 1 Level in Patients Coinfected with HIV and Hepatitis C Virus: A CORIST‐ANRS HC1 Trial

Author: Cécile Goujard, Philippe Sogni, Fabien Zoulim, Geneviève Chêne, Magali Bouvier-Alias, Philippe Morlat, Alain Pruvost, Sophie Pérusat, Christopher Payan, Jean-Marc Tréluyer, Régis Lassalle, Eric Bonnet, Henri Benech, and Dominique Salmon-Ceron
Subjects: Adult, Male, Microbiology (medical), Hepatitis C virus, Hepacivirus, HIV Infections, medicine.disease_cause, Antiviral Agents, Virus, chemistry.chemical_compound, Interferon, Ribavirin, medicine, Humans, Reverse-transcriptase inhibitor, biology, business.industry, Stavudine, virus diseases, Hepatitis C, Chronic, Middle Aged, Viral Load, biology.organism_classification, Hepatitis C, Virology, digestive system diseases, CD4 Lymphocyte Count, Treatment Outcome, Infectious Diseases, chemistry, HIV-1, RNA, Viral, Drug Therapy, Combination, Female, Interferons, business, Viral load, Follow-Up Studies, medicine.drug
Abstract: A randomized, open-label trial was performed to study virological and intracellular interactions between stavudine and ribavirin in 30 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Patients were randomized to receive either interferon and ribavirin or no treatment for HCV infection for 3 months. Intracellular peripheral blood mononuclear cells' stavudine-triphosphate (TP) concentrations were assessed. Plasma HIV RNA levels did not change significantly between baseline and month 3. There was a nonstatistically significant trend for a lower median residual concentration of intracellular stavudine-TP in the treated group, compared with the control group. The same trend was also observed for peak concentrations. Coprescription of ribavirin and stavudine has no short-term impact on plasma HIV RNA level in HIV-HCV-coinfected patients treated with stavudine as a part of their antiretroviral treatment; this coprescription can be safely used, although an in vivo interaction between ribavirin and stavudine is possible.
Published: 2003
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33. Clinical utility of total HCV core antigen quantification: A new indirect marker of HCV replication

Author: Gaston Picchio, Patrick Larderie, Jean-Michel Pawlotsky, Christophe Hézode, Harel Dahari, Lawrence M. Blatt, Daniel Dhumeaux, Keyur Patel, Magali Bouvier-Alias, Stéphanie Beaucourt, Avidan U. Neumann, and John G. McHutchison
Subjects: Hepatology, biology, business.industry, medicine.drug_class, Hepacivirus, Hepatitis C virus, virus diseases, Hepatitis C, medicine.disease, biology.organism_classification, medicine.disease_cause, Monoclonal antibody, Virology, digestive system diseases, Viral replication, Antigen, Immunology, medicine, Viral disease, business, Viral load
Abstract: Hepatitis C virus (HCV) RNA detection, viral load quantification, and HCV genotyping are widely used in clinical practice. Recently, the availability of an anticore antigen (Ag) monoclonal antibody allowed development of an enzyme-linked immunosorbent assay (ELISA) detecting and quantifying total HCV core Ag in peripheral blood of HCV-infected patients. The aims of the present study were to investigate the biologic significance of this new marker in HCV infection, to establish the intrinsic performance of the current assay, and to determine its potential utility in the management of HCV-infected patients. A panel of infected sera calibrated to the World Health Organization International Standard and 657 serum samples from infected patients receiving antiviral treatment were studied. We showed that total HCV core Ag quantification is an accurate, precise, and specific indirect marker of HCV replication. We estimated that 1 pg/mL of total HCV core Ag is equivalent to approximately 8,000 HCV RNA international units (IU)/mL, although minor between-patient differences may exist. In conclusion, total HCV core Ag quantification can be used in the various indications of viral load monitoring, including the evaluation of baseline viral load before therapy, the assessment of the virologic response to antiviral treatment, and the study of early viral kinetics during therapy. Nevertheless, the total HCV core Ag assay cannot be used as a marker of viral replication for HCV RNA values below 20,000 IU/mL, limiting its use in the monitoring of late events during and after antiviral treatment.
Published: 2002
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34. Clinical utility of hepatitis C virus core antigen quantification in patients with chronic hepatitis C

Author: Lila Poiteau, Magali Bouvier-Alias, Alexandre Soulier, Stéphane Chevaliez, and Jean-Michel Pawlotsky
Subjects: Adult, Male, Adolescent, Hepatitis C virus, Hepacivirus, medicine.disease_cause, Sensitivity and Specificity, Young Adult, Antigen, Virology, Genotype, medicine, Humans, In patient, Antigens, Viral, Aged, Aged, 80 and over, Immunoassay, medicine.diagnostic_test, business.industry, Clinical Laboratory Techniques, Viral Core Proteins, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, digestive system diseases, Infectious Diseases, Nat, Immunology, Female, Hcv core antigen, business
Abstract: Background Hepatitis C virus (HCV) core antigen has been proposed as a surrogate marker of HCV replication. HCV core antigen detection and quantification can thus theoretically be used instead of nucleic acid testing (NAT) to diagnose infection and manage antiviral therapy, with several advantages compared to HCV RNA assays. HCV core antigen can now be easily detected and quantified by means of a chemiluminescent microparticle immunoassay on the Abbott Architect device. Objective The aim of the present study was to evaluate the clinical performance of the Architect HCV Ag assay for the detection and quantification of HCV core antigen in patients with chronic HCV genotype 1–6 infections. Results The Architect HCV Ag assay had a specificity of 100% (95%CI: 97.8–100%). HCV core antigen levels were not influenced by the HCV genotype. The lower limit of detection of 3 fmol/L corresponded to approximately 1000 IU/mL of HCV RNA, regardless of the real-time PCR assay used. HCV core antigen and HCV RNA levels correlated for HCV genotype 1–4 ( r = 0.89 and r = 0.88 for the m 2000 and the CAP/CTM v2.0 assay, respectively). Conclusions The Architect HCV Ag assay is highly specific and easy to perform. It represents a valuable screening, diagnostic and monitoring tool, especially in the era of new all-oral, interferon-free antiviral strategies that do not require high analytical sensitivity.
Published: 2014

35. Standardization of Hepatitis C Virus RNA Quantification

Author: Jean-Michel Pawlotsky, Christophe Hézode, Daniel Dhumeaux, Jocelyne Rémiré, Magali Bouvier-Alias, and Françoise Darthuy
Subjects: Hepacivirus, Hepatitis C virus, medicine.disease_cause, Antiviral Agents, Virus, Flaviviridae, chemistry.chemical_compound, Ribavirin, Humans, Medicine, Interferon alfa, Hepatology, biology, business.industry, Interferon-alpha, virus diseases, RNA, Reference Standards, biology.organism_classification, Hepatitis C, Virology, Genetic Techniques, chemistry, RNA, Viral, Drug Therapy, Combination, business, Viral load, medicine.drug
Abstract: It was recently recommended that hepatitis C virus (HCV) RNA quantification be used to tailor the duration of combined interferon alfa (IFN-alpha)/ribavirin therapy in patients infected by HCV genotypes 1, 4, and 5. This recommendation has been difficult to implement in the absence of standardized quantitative units for HCV RNA. The aim of this work was to define clinically relevant HCV RNA loads in standardized international units (IU), for use in routine clinical and research applications based on standardized quantitative assays. Two hepatitis C virus RNA quantitative assays were used: (1) the Superquant assay (National Genetics Institute, Los Angeles, CA), for which possibly relevant thresholds were established; and (2) the semi-automated Cobas Amplicor HCV Monitor assay version 2.0 (Cobas v2.0, Roche Molecular Systems, Pleasanton, CA) that measures HCV RNA loads in IU/mL. Quantification in the Cobas v2.0 assay was linear over the entire range of values tested, including viral loads higher than 850,000 IU/mL after 100-fold dilution. The accuracy and precision of the measures in IU/mL were satisfactory with Cobas v2.0. The results obtained with Superquant and Cobas v2.0 correlated (r =.932; P
Published: 2000
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36. P0843 : On-treatment viral kinetics do not predict SVR in patients with advanced liver disease receiving sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks

Author: Christophe Hézode, Cyrille Feray, M. Francois, Isaac Ruiz, Magali Bouvier-Alias, Stéphane Chevaliez, Jean-Michel Pawlotsky, Ariane Mallat, and G. Scoazec
Subjects: Simeprevir, medicine.medical_specialty, Daclatasvir, Hepatology, Sofosbuvir, business.industry, medicine.disease, Viral kinetics, Gastroenterology, Liver disease, Internal medicine, medicine, In patient, business, medicine.drug
Published: 2015
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37. The Cobas AmpliPrep/Cobas TaqMan HCV Test, Version 2.0, Real-Time PCR Assay Accurately Quantifies Hepatitis C Virus Genotype 4 RNA

Author: Jean-Dominique Poveda, Stéphane Chevaliez, Jean-Michel Pawlotsky, Magali Bouvier-Alias, Alexandre Soulier, and Christophe Rodriguez
Subjects: Microbiology (medical), Genotype, Hepacivirus, Hepatitis C virus, medicine.disease_cause, Real-Time Polymerase Chain Reaction, Virology, BDNA test, Medicine, Humans, biology, business.industry, RNA, virus diseases, Hepatitis C, Hepatitis C, Chronic, Viral Load, biology.organism_classification, medicine.disease, digestive system diseases, Real-time polymerase chain reaction, RNA, Viral, business, Viral load
Abstract: Accurate hepatitis C virus (HCV) RNA quantification is mandatory for the management of chronic hepatitis C therapy. The first-generation Cobas AmpliPrep/Cobas TaqMan HCV test (CAP/CTM HCV) underestimated HCV RNA levels by >1-log 10 international units/ml in a number of patients infected with HCV genotype 4 and occasionally failed to detect it. The aim of this study was to evaluate the ability of the Cobas AmpliPrep/Cobas TaqMan HCV test, version 2.0 (CAP/CTM HCV v2.0), to accurately quantify HCV RNA in a large series of patients infected with different subtypes of HCV genotype 4. Group A comprised 122 patients with chronic HCV genotype 4 infection, and group B comprised 4 patients with HCV genotype 4 in whom HCV RNA was undetectable using the CAP/CTM HCV. Each specimen was tested with the third-generation branched DNA (bDNA) assay, CAP/CTM HCV, and CAP/CTM HCV v2.0. The HCV RNA level was lower in CAP/CTM HCV than in bDNA in 76.2% of cases, regardless of the HCV genotype 4 subtype. In contrast, the correlation between bDNA and CAP/CTM HCV v2.0 values was excellent. CAP/CTM HCV v2.0 accurately quantified HCV RNA levels in the presence of an A-to-T substitution at position 165 alone or combined with a G-to-A substitution at position 145 of the 5′ untranslated region of HCV genome. In conclusion, CAP/CTM HCV v2.0 accurately quantifies HCV RNA in genotype 4 clinical specimens, regardless of the subtype, and can be confidently used in clinical trials and clinical practice with this genotype.
Published: 2013

38. Liver stiffness diminishes with antiviral response in chronic hepatitis C

Author: Magali Bouvier-Alias, Laurent Castera, Christophe Hézode, Isabelle Rosa, Françoise Roudot-Thoraval, Ariane Mallat, Dominique Roulot, Vincent Leroy, Jean-Michel Pawlotsky, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service d'hépatologie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de santé publique [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 Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-entérologie, CHI Créteil, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépato-gastroentérologie, and CHU Grenoble-Université Grenoble Alpes (UGA)
Subjects: medicine.medical_specialty, Cirrhosis, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Pharmacology (medical), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Prospective cohort study, Hepatology, business.industry, Ribavirin, Odds ratio, Hepatitis C, medicine.disease, 3. Good health, Surgery, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Hepatic fibrosis, Transient elastography, Off Treatment, business
Abstract: Aliment Pharmacol Ther 2011; 34: 656–663 Summary Background Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Aim To assess prospectively the kinetics of liver stiffness in treated patients with chronic hepatitis C and compare them with the viral kinetics on treatment and with the final outcome of therapy. Methods 91 patients with chronic hepatitis C with significant fibrosis (>7.0 kPa) at baseline were included. They received therapy with pegylated interferon-α and ribavirin. The kinetics of liver stiffness were characterized during therapy and thereafter by means of Fibroscan, and compared with the virological responses at weeks 4, 12, 24, end of treatment and 12 and 24 weeks after. Results A significant liver stiffness decrease was observed during therapy, which continued after treatment only in patients who achieved a sustained virological response. In this group, the median intra-patient decrease relative to baseline at the end of follow-up was −3.4 kPa, vs−1.8 kPa in the patients who did not achieve an SVR. Similar dynamics were observed in cirrhotic and non-cirrhotic patients. In multivariate analysis, only the SVR was associated with long-term improvement of liver stiffness (odds ratio: 3.10; 95% confidence interval: 1.20–8.02, P = 0.019). Conclusions In patients with advanced fibrosis at the start of therapy, liver stiffness is significantly reduced during treatment, but improvement continues off treatment only in patients who achieve a sustained virological response. Liver stiffness assessment earlier than 6 months after the end of therapy does not appear to be clinically meaningful.
Published: 2011
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39. High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

Author: Laurent Alric, Vincent Leroy, Bruno Costes, Magali Bouvier–Alias, Patrice Couzigou, Mariem Charaf–Eddine, Stéphanie Rouanet, Jean-Pierre Bronowicki, Stéphane Chevaliez, Jean-Michel Pawlotsky, Isabelle Rosa, Christophe Hézode, Philippe Mathurin, Juliette Foucher, Alexandre Soulier, Gérard Babany, Albert Tran, Ariane Mallat, 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) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'hépato-gastro-entérologie [APHP 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), Service de Biochimie [Mondor], Produits Roche, Roche, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Pôle Digestif, Hôpital Archet 2 [Nice] (CHU), Service d'hépato-gastro-entérologie, CHI Créteil, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service de médecine interne et maladies digestives, CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, This study is investigator-initiated. It has been funded by Roche France, which provided the study drugs, and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Time Factors, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Interferon, Pegylated interferon, nonresponder, Genotype, Odds Ratio, Medicine, 0303 health sciences, education.field_of_study, Hepatitis C virus, Hepatitis C, Middle Aged, Viral Load, Recombinant Proteins, 3. Good health, Phenotype, Treatment Outcome, RNA, Viral, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, high-dose pegylated IFN-α, medicine.drug, Adult, medicine.medical_specialty, Population, Context (language use), IL28B genotype, Interferon alpha-2, Antiviral Agents, Risk Assessment, 03 medical and health sciences, Internal medicine, Drug Resistance, Viral, Ribavirin, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, Aged, 030304 developmental biology, Chi-Square Distribution, Hepatology, business.industry, Interleukins, Interferon-alpha, Hepatitis C, Chronic, medicine.disease, Logistic Models, chemistry, Immunology, Linear Models, Interferons, business
Abstract: International audience; BACKGROUND & AIMS: In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown. METHODS: Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied. RESULTS: At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log(10) decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24. CONCLUSIONS: High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population.
Published: 2011
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40. Interpretation of Real-Time PCR Results for Hepatitis C Virus RNA When Viral Load Is Below Quantification Limits

Author: Françoise Lunel, Françoise Stoll-Keller, Ronald Colimon, Sophie Vallet, Jean-Jacques Lefrère, Pascale Trimoulet, Jacques Izopet, Evelyne Schvoerer, Magali Bouvier-Alias, Marie-Laure Chaix, Hélène Leguillou-Guillemette, Yazid Baazia, Gilles Duverlie, Vincent Thibault, Cécile Henquell, Jean-Michel Pawlotsky, Arielle R. Rosenberg, Françoise Bouchardeau, Syria Laperche, Elisabeth André-Garnier, Anne-Marie Roque-Afonso, Bruno Pozzetto, Catherine Gaudy-Graffin, Michel Branger, 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) (AP-HP), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, CHU Pontchaillou [Rennes], Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, 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, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Strasbourg], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Service de bactériologie-Virologie-Hygiène [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], VIROLOGIE, CHU Toulouse [Toulouse], Institut National de la Transfusion Sanguine [Paris] (INTS), CHU Amiens-Picardie, Hôtel-Dieu de Nantes, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Jean Monnet - Saint-Étienne (UJM), 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), SCHVOERER, Evelyne, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Transfusion Sanguine [Paris] ( INTS ) -Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ), Service de virologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Hôpital Paul Brousse, Unité de Virologie clinique et fondamentale EA 4294, Laboratoire de Virologie, CHU Strasbourg, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Virus, pseudo-virus: Morphogénèse et Antigénicité, Université de Tours-EA3856, Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Hôpital Avicenne-Université Paris 13 ( UP13 ), Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Subjects: Serial dilution, Hepacivirus, MESH : Viral Load, medicine.disease_cause, MESH : Hepacivirus, MESH : Virology, law.invention, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Hepacivirus, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Viral Load, 3. Good health, Real-time polymerase chain reaction, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, 030211 gastroenterology & hepatology, MESH: Viral Load, MESH : Decision Support Techniques, Viral load, Microbiology (medical), Hepatitis C virus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Virus, Decision Support Techniques, 03 medical and health sciences, Flaviviridae, Virology, medicine, MESH : RNA, Viral, Humans, MESH: Humans, 030306 microbiology, MESH : Humans, MESH: Decision Support Techniques, biology.organism_classification, Molecular biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Virology
Abstract: Hepatitis C virus RNA quantification results obtained in 18 laboratories using real-time PCR methods with 10 negative samples and 22 sample dilutions (viral loads of 0.5 to 500 IU/ml) showed a score of correct results of up to 93.5%. However, 55.6% of the laboratories did not follow the recommendations for the interpretation of their results, leading to ambiguous conclusions.
Published: 2011
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41. Performance of the Abbott real-time PCR assay using m2000sp and m2000rt for hepatitis C virus RNA quantification.: m2000SP/m2000RT FOR HCV RNA QUANTIFICATION

Author: Stéphane Chevaliez, Jean-Michel Pawlotsky, Magali Bouvier-Alias, 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) (AP-HP), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and This work is part of the activity of the VIRGIL European Network of Excellence on Antiviral Drug Resistance supported by a grant (LSHM-CT-2004-503359) from the Priority 1 'Life Sciences, Genomics and Biotechnology for Health' programme in the 6th Framework Programme of the European Union
Subjects: Microbiology (medical), Hepacivirus, Hepatitis C virus, medicine.disease_cause, Polymerase Chain Reaction, Sensitivity and Specificity, Virus, 03 medical and health sciences, Flaviviridae, 0302 clinical medicine, Virology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, Reproducibility of Results, RNA, Hepatitis C, Hepatitis C, Chronic, Viral Load, biology.organism_classification, medicine.disease, Molecular biology, 3. Good health, Real-time polymerase chain reaction, RNA, Viral, 030211 gastroenterology & hepatology, Viral load
Abstract: Quantification of hepatitis C virus (HCV) RNA is essential for the everyday management of chronic hepatitis C therapy. “Real-time” PCR techniques are potentially more sensitive than classical PCR techniques, are not prone to carryover contamination, and have a consistently wider dynamic range of quantification. Thus, they are rapidly replacing other technologies for routine quantification of HCV RNA. We extensively evaluated the intrinsic characteristics and clinical performance of the m 2000 sp - m 2000 rt Abbott real-time PCR platform for HCV RNA quantification. The study shows that the m 2000 sp - m 2000 rt platform is sensitive, specific, and precise; that the results are reproducible; and that the platform has a broad dynamic range of quantification. When comparing HCV RNA levels measured in the same individuals with the m 2000 sp - m 2000 rt platform and the third-generation branched-DNA assay, a trend toward a modest overestimation of HCV RNA levels was observed in the m 2000 sp - m 2000 rt platform in all genotypes except genotype 5. The differences, however, were unlikely to have any impact in clinical practice. In conclusion, our study shows that the Abbott m 2000 real-time PCR system for HCV RNA quantification is sensitive, specific, and precise; that the results are reproducible; and that the platform's broad dynamic range of quantification is well suited to HCV RNA monitoring in the clinical setting.
Published: 2009
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42. Performance of the Cobas AmpliPrep/Cobas TaqMan real-time PCR assay for hepatitis B virus DNA quantification

Author: Stéphane Chevaliez, Jean-Michel Pawlotsky, Magali Bouvier-Alias, Syria Laperche, 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) (AP-HP), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Guellaen, Georges
Subjects: Microbiology (medical), Hepatitis B virus, Genotype, MESH: Hepatitis B, Chronic, medicine.disease_cause, Polymerase Chain Reaction, Sensitivity and Specificity, Virus, MESH: Prognosis, law.invention, MESH: Genotype, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, Orthohepadnavirus, law, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Polymerase chain reaction, 0303 health sciences, MESH: Humans, biology, 030306 microbiology, virus diseases, Reproducibility of Results, MESH: Polymerase Chain Reaction, Hepatitis B, biology.organism_classification, medicine.disease, Prognosis, Molecular biology, MESH: Sensitivity and Specificity, digestive system diseases, 3. Good health, MESH: DNA, Viral, MESH: Reproducibility of Results, MESH: Hepatitis B virus, Real-time polymerase chain reaction, Hepadnaviridae, DNA, Viral, 030211 gastroenterology & hepatology
Abstract: Hepatitis B virus (HBV) DNA quantification is used to establish the prognosis of chronic HBV-related liver disease, to identify those patients who need to be treated, and to monitor the virologic response and resistance to antiviral therapies. Real-time PCR-based assays are gradually replacing other technologies for routine quantification of HBV DNA in clinical practice. The goal of this study was to evaluate the intrinsic characteristics and clinical performance of the real-time PCR Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) platform for HBV DNA quantification. Specificity was satisfactory (95% confidence interval, 98.1 to 100%). Intra-assay coefficients of variation ranged from 0.22% to 2.68%, and interassay coefficients of variation ranged from 1.31% to 4.13%. Quantification was linear over the full dynamic range of quantification of the assay (1.7 to 8.0 log 10 IU/ml) and was not affected by dilution. The assay was accurate regardless of the HBV genotype. Samples containing HBV DNA levels above 4.5 log 10 IU/ml were slightly underestimated relative to another accurate assay based on branched-DNA technology, but this is unlikely to have noteworthy clinical implications. Thus, the CAP/CTM HBV DNA assay is sensitive, specific, and reproducible, and it accurately quantifies HBV DNA levels in patients chronically infected by HBV genotypes A to F. Samples with HBV DNA concentrations above the upper limit of quantification need to be diluted and then retested. Broad use of fully automated real-time PCR assays should improve the management of patients with chronic HBV infection.
Published: 2008
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43. Overestimation and underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method

Author: Magali Bouvier-Alias, Rozenn Brillet, Stéphane Chevaliez, and Jean-Michel Pawlotsky
Subjects: Genotype, Hepacivirus, Hepatitis C virus, medicine.disease_cause, Polymerase Chain Reaction, Virus, Flaviviridae, Reference Values, medicine, Humans, DNA Primers, Hepatology, biology, RNA, Reproducibility of Results, Hepatitis C, Hepatitis C, Chronic, Viral Load, biology.organism_classification, medicine.disease, Virology, Molecular biology, Real-time polymerase chain reaction, DNA, Viral, RNA, Viral, Viral load
Abstract: The quantification of hepatitis C virus (HCV) RNA is essential for the everyday management of chronic hepatitis C therapy. Real-time polymerase chain reaction (PCR) techniques are potentially more sensitive than classical PCR techniques, are not prone to carryover contamination, and have a consistently wider dynamic range of quantification. Thus, they are rapidly replacing other technologies for the routine quantification of HCV RNA. We extensively evaluated the intrinsic characteristics and clinical performance of Cobas Ampliprep/Cobas TaqMan (CAP/CTM), the most widely used real-time PCR assay for HCV RNA quantification. This study shows that CAP/CTM is sensitive, specific, precise, and reproducible and has a broad dynamic range of quantification well suited to HCV RNA monitoring in clinical practice. However, we identified 2 technical issues that will have an impact in clinical practice. First, the CAP/CTM assay overestimates HCV RNA levels in undiluted patient samples by approximately 0.6 log10 international units per milliliter on average, and this overestimation increases with the viral load. Second, the CAP/CTM assay substantially underestimates HCV RNA levels in approximately 15% of genotype 2 samples and 30% of genotype 4 samples, probably because of mismatches with the target sequences due to the primer and/or probe design. Conclusion: As the CAP/CTM platform is widely available, easy to use, and suited to high-throughput screening for viral genomes, the manufacturer should improve the HCV RNA kit to resolve these 2 important technical issues that may affect everyday management of hepatitis C therapy. (HEPATOLOGY 2007.)
Published: 2007

44. Efficacy and safety of adefovir dipivoxil 20 mg daily in HBeAg-positive patients with lamivudine-resistant hepatitis B virus and a suboptimal virological response to adefovir dipivoxil 10 mg daily

Author: Daniel Dhumeaux, Elie-Serge Zafrani, Stéphane Chevaliez, Jean-Michel Pawlotsky, Françoise Roudot-Thoraval, Christophe Hézode, Magali Bouvier-Alias, and Rozenn Brillet
Subjects: Adult, Male, HBsAg, medicine.medical_specialty, Hepatitis B virus, Adolescent, Organophosphonates, Biology, medicine.disease_cause, Gastroenterology, Antiviral Agents, Hepatitis B, Chronic, Orthohepadnavirus, Internal medicine, Drug Resistance, Viral, medicine, Adefovir, Humans, Hepatitis B e Antigens, Aged, Hepatology, Reverse-transcriptase inhibitor, Dose-Response Relationship, Drug, Adenine, virus diseases, Lamivudine, Alanine Transaminase, Hepatitis B, Middle Aged, medicine.disease, biology.organism_classification, digestive system diseases, Treatment Outcome, HBeAg, Immunology, DNA, Viral, Reverse Transcriptase Inhibitors, Female, medicine.drug
Abstract: Background/Aims Some patients receiving adefovir at the approved dose of 10mg daily for chronic hepatitis B have a "suboptimal" virological response characterized by a slow and moderate decrease in viral replication. Methods We assessed the efficacy and safety of adefovir 20mg daily in patients with hepatitis B e antigen-positive chronic hepatitis B resistant to lamivudine and a suboptimal virological response to adefovir 10mg daily add-on. Results No amino acid substitutions known to confer adefovir resistance were found in these patients. In the five treated patients, the switch from 10mg to 20mg of adefovir daily significantly improved antiviral efficacy (−1.78±0.28 log international units/mL versus −3.73±0.51 log international units/mL, respectively, p =0.0039), and alanine aminotransferase levels normalized in all but one of the patients. No signs of renal dysfunction occurred. Conclusions These results suggest: (i) that suboptimal responses to adefovir 10mg daily are due to underdosing; and (ii) that increasing the adefovir dose to 20mg daily is beneficial and safe in patients with lamivudine-resistant HBV and a suboptimal response to adefovir 10mg daily, especially when alanine aminotransferase levels are elevated and/or the liver disease is severe or rapidly progressive. Careful monitoring of renal function is necessary.
Published: 2006

45. Multicenter Performance Evaluation of a New TaqMan PCR Assay for Monitoring Human Immunodeficiency Virus RNA Load▿

Author: Stefan Zeuzem, Luc Perrin, Giuseppe Colucci, Magali Bouvier-Alias, Christoph Sarrazin, and Jean-Michel Pawlotsky
Subjects: Microbiology (medical), Analysis of Variance, biology, Serial dilution, RNA, HIV Infections, Viral Load, biology.organism_classification, Virology, Molecular biology, Polymerase Chain Reaction, Sensitivity and Specificity, Virus, law.invention, law, Lentivirus, TaqMan, HIV-1, Humans, RNA, Viral, Human Immunodeficiency Virus RNA, Reagent Kits, Diagnostic, Viral load, Polymerase chain reaction
Abstract: A TaqMan real-time PCR assay, the COBAS TaqMan human immunodeficiency virus (HIV) (HPS-CTMHIV) PCR assay, recently developed for the quantification of HIV type 1 RNA in plasma, was evaluated in comparison with the licensed COBAS AMPLICOR HIV-1 MONITOR (CAHIM) assay. In this study, we have analyzed the tests' sensitivities, precisions, and linearities using multiple replicates of a standard panel of HIV RNA covering a 7-logarithm range of concentrations, as well as serial threefold dilutions of high-titer clinical samples. The subtype inclusivity was also investigated, using a panel of subtypes A to H, while a collection of 160 clinical samples was analyzed to assess the tests' specificities and the systems' similarities. The results of these experiments showed that the HPS-CTMHIV assay has a sensitivity of 53 copies/ml (95% hit rate), 100% specificity, and good intra- and interassay precision. The results of the HPS-CTMHIV assay were linear in the 50- to 10 7 -copies/ml range, with a correlation coefficient ( R ) for expected versus observed results of 0.98. Compared to the CAHIM assay, the HPS-CTMHIV assay showed a high correlation ( R = 0.99) across the dynamic range of RNA concentrations that, for the CAHIM assay, requires two different sample preparations. Equivalent performances were also observed for the two systems in the detection and quantification of HIV subtypes A to H. These data indicate that the HPS-CTMHIV assay may be one of the tests of choice for monitoring viral load throughout the course of HIV infection and during highly active antiretroviral therapy.
Published: 2006

46. Dynamic range of hepatitis C virus RNA quantification with the Cobas Ampliprep-Cobas Amplicor HCV Monitor v2.0 assay

Author: Jocelyne Rémiré, Bertrand Pellegrin, Christophe Hézode, Magali Bouvier-Alias, Alexandre Soulier, Karine Gourlain, Françoise Darthuy, and Jean-Michel Pawlotsky
Subjects: Microbiology (medical), Hepacivirus, Hepatitis C virus, Alpha interferon, Interferon alpha-2, medicine.disease_cause, Antiviral Agents, chemistry.chemical_compound, Flaviviridae, Automation, Virology, Ribavirin, medicine, Humans, biology, RNA, virus diseases, Interferon-alpha, Nucleic acid amplification technique, Hepatitis C, Chronic, Viral Load, biology.organism_classification, Molecular biology, digestive system diseases, Recombinant Proteins, chemistry, RNA, Viral, Drug Therapy, Combination, Reagent Kits, Diagnostic, Viral load, Nucleic Acid Amplification Techniques
Abstract: Accurate quantification of hepatitis C virus (HCV) RNA is needed in clinical practice to decide whether to continue or stop pegylated interferon-α-ribavirin combination therapy at week 12 of treatment for patients with chronic hepatitis C. Currently the HCV RNA quantification assay most widely used worldwide is the Amplicor HCV Monitor v2.0 assay (Roche Molecular Systems, Pleasanton, Calif.). The HCV RNA extraction step can be automated in the Cobas Ampliprep device. In this work, we show that the dynamic range of HCV RNA quantification of the Cobas Ampliprep/Cobas Amplicor HCV Monitor v2.0 procedure is 600 to 200,000 HCV RNA IU/ml (2.8 to 5.3 log IU/ml), which does not cover the full range of HCV RNA levels in infected patients. Any sample containing more than 200,000 IU/ml (5.3 log IU/ml) must thus be retested after dilution for accurate quantification. These results emphasize the need for commercial HCV RNA quantification assays with a broader range of linear quantification, such as real-time PCR-based assays.
Published: 2005

47. Clinical utility of total HCV core antigen quantification: a new indirect marker of HCV replication

Author: Magali, Bouvier-Alias, Keyur, Patel, Harel, Dahari, Stéphanie, Beaucourt, Patrick, Larderie, Lawrence, Blatt, Christophe, Hezode, Gaston, Picchio, Daniel, Dhumeaux, Avidan U, Neumann, John G, McHutchison, and Jean-Michel, Pawlotsky
Subjects: Kinetics, Genotype, Viral Core Proteins, Humans, RNA, Viral, Hepacivirus, Virus Replication, Hepatitis C, Sensitivity and Specificity, Biomarkers
Abstract: Hepatitis C virus (HCV) RNA detection, viral load quantification, and HCV genotyping are widely used in clinical practice. Recently, the availability of an anticore antigen (Ag) monoclonal antibody allowed development of an enzyme-linked immunosorbent assay (ELISA) detecting and quantifying total HCV core Ag in peripheral blood of HCV-infected patients. The aims of the present study were to investigate the biologic significance of this new marker in HCV infection, to establish the intrinsic performance of the current assay, and to determine its potential utility in the management of HCV-infected patients. A panel of infected sera calibrated to the World Health Organization International Standard and 657 serum samples from infected patients receiving antiviral treatment were studied. We showed that total HCV core Ag quantification is an accurate, precise, and specific indirect marker of HCV replication. We estimated that 1 pg/mL of total HCV core Ag is equivalent to approximately 8,000 HCV RNA international units (IU)/mL, although minor between-patient differences may exist. In conclusion, total HCV core Ag quantification can be used in the various indications of viral load monitoring, including the evaluation of baseline viral load before therapy, the assessment of the virologic response to antiviral treatment, and the study of early viral kinetics during therapy. Nevertheless, the total HCV core Ag assay cannot be used as a marker of viral replication for HCV RNA values below 20,000 IU/mL, limiting its use in the monitoring of late events during and after antiviral treatment.
Published: 2002

48. The Cobas AmpliPrep-Cobas TaqMan real-time polymerase chain reaction assay fails to detect hepatitis C virus RNA in highly viremic genotype 4 clinical samples

Author: Laurent Castera, Magali Bouvier-Alias, Stéphane Chevaliez, and Jean-Michel Pawlotsky
Subjects: Base Sequence, Genotype, Hepatology, Hepatitis B virus DNA polymerase, Cobas taqman, Molecular Sequence Data, Hepacivirus, Biology, Hepatitis C, Polymerase Chain Reaction, Virology, Reverse transcription polymerase chain reaction, Hepatitis C virus RNA, Humans, RNA, Viral, REAL-TIME POLYMERASE CHAIN REACTION ASSAY, Sequence Alignment
Published: 2008
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49. 525 Hepatitis virus C RNA quantification by automated cobas ampliprep-cobas taqman 48 (CAP-CTM) real-time PCR assay. An evaluation of performance

Author: Magali Bouvier-Alias, Stéphane Chevaliez, Jean-Michel Pawlotsky, G. Dameron, E. Darthuy, and J. Remire
Subjects: Real-time polymerase chain reaction, Hepatology, Cobas taqman, Hepatitis C virus, Rna quantification, medicine, TaqMan, Biology, medicine.disease_cause, Virology
Published: 2006
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50. P.197 Baseline neutralizing responses predict the virological response to pegylated interferon alpha-ribavirin combination therapy

Author: Yoann Morice, Jean-Pierre Bronowicki, Jean-Michel Pawlotsky, L. Barbotte, François-Loïc Cosset, F. Montestruc, I. Lonjon-Domanec, Dimitri Lavillette, Birke Bartosch, P. Woerther, Magali Bouvier-Alias, and Christophe Hézode
Subjects: medicine.medical_specialty, Combination therapy, business.industry, Ribavirin, Alpha (ethology), Gastroenterology, Virological response, chemistry.chemical_compound, Infectious Diseases, chemistry, Pegylated interferon, Virology, Internal medicine, medicine, business, medicine.drug
Published: 2006
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