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1. Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021

Author: Brice Mastrovito, Chloé Naimi, Leslie Kouam, Xavier Naudot, Lucie Fournier, Guillaume Spaccaferri, Jean-Christophe Plantier, Anaïs Soares, Fabienne De Oliveira, Marie Gueudin, Véronique Jacomo, Céline Leroy, Alice Moisan, Mélanie Martel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Eurofins Biomnis, Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Agence Régionale de Santé de Normandie [Caen] (ARS Normandie), and Mzembaba, Sandy
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiology, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Disease Outbreaks, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, France, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged
Abstract: International audience; Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.
Published: 2022

2. Transmission et circulation d'un recombinant SARS-CoV-2 Deltacron XD en Normandie

Author: Moisan, Alice, Mastrovito, Brice, de Oliveira, Fabienne, Martel, Mélanie, Hedin, Hugues, Leoz, Marie, Nesi, Nicolas, Schaeffer, Justine, Gouilh, Meriadeg, Plantier, Jean-Christophe, Mzembaba, Sandy, Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Service de Virologie [CHU Caen], CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience
Published: 2022

3. High rate of hepatitis C virus and human immunodeficiency virus false‐positive results in serologic screening in sub‐Saharan Africa: adverse impact on the blood supply

Author: Daniel Candotti, Sekou Oumar Coulibaly, Hadiza Soumana, Virginie Sauvage, Edward L. Murphy, Guy Olivier Mbensa, Claude Tagny-Tayou, Pascal Bizimana, Syria Laperche, Aimée Olivat Rakoto Alson, Mohamed Abdallahi Boullahi, Pierre Cappy, Institut National de la Transfusion Sanguine [Paris] (INTS), 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)-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), 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, National Blood Center [Nouakchott, Mauritania] (NBC), National Blood Center [Bujumbura, Burundi] (NBC), National Blood Center [Kinshasa, Democratic Republic of the Congo] (NBC), National Blood Center [Bamako, Mali] (NBC), National Blood Center [Antananarivo, Madagascar] (NBC), National Blood Center [Niamey, Niger] (NBC), University of Yaoundé [Cameroun], University of California [San Francisco] (UC San Francisco), University of California (UC), Vitalant Research Institute [San Francisco], University of California [San Francisco] (UCSF), University of California, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Candotti, Daniel
Subjects: Adult, Male, Hepatitis C virus, Hepacivirus, Immunology, Blood Donors, HIV Infections, HIV Antibodies, 030204 cardiovascular system & hematology, medicine.disease_cause, Donor Selection, Serology, 03 medical and health sciences, 0302 clinical medicine, Antigen, parasitic diseases, medicine, Humans, Immunology and Allergy, False Positive Reactions, Africa South of the Sahara, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, High rate, biology, business.industry, Donor selection, Blood Screening, virus diseases, Hematology, Hepatitis C Antibodies, biology.organism_classification, Hepatitis C, Virology, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Female, Antibody, business, 030215 immunology
Abstract: International audience; Background: False positivity in blood screening may cause unnecessary deferral of healthy donors and exacerbate blood shortages. An international multicenter study was conducted to estimate the frequency of HCV and HIV false seropositivity in seven African countries (Burundi, Cameroon, Democratic Republic of Congo, Madagascar, Mali, Mauritania, and Niger).Study design and methods: Blood donations were tested for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) with rapid detection tests (RDTs), third-generation enzyme immunoassays (EIAs), or fourth-generation EIAs. HCV (456/16,613 [2.74%]) and HIV (249/16,675 [1.49%]) reactive samples were then confirmed with antigen/antibody assays, immunoblots, and nucleic acid testing. Partial viral sequences were analyzed when possible.Results: The HCV reactivity rate with RDTs was significantly lower than with EIAs (0.55% vs. 3.52%; p < 0.0001). The HIV reactivity rate with RDTs was lower than with third-generation EIAs (1.02% vs. 2.38%; p < 0.0001) but similar to a fourth-generation assay (1.09%). Only 16.0% (57/357) and 21.5% (38/177) of HCV and HIV initial reactive samples, respectively, were repeatedly reactive. HCV and HIV infections were confirmed in 13.2% and 13.7%, respectively, of repeated reactive donations. The predominant HCV genotype 2 and 4 strains in West and Central Africa showed high genetic variability. HIV-1 subtype CRF02_AG was most prevalent.Conclusion: High rates (>80%) of unconfirmed anti-HCV and anti-HIV reactivity observed in several sub-Saharan countries highlights the need for better testing and confirmatory strategies for donors screening in Africa. Without confirmatory testing, HCV and HIV prevalence in African blood donors has probably been overestimated.
Published: 2019

4. False-negative Results of Human Immunodeficiency Virus (HIV) Rapid Testing in HIV Controllers

Author: Mehdi Hage-Sleiman, Olivier Lambotte, Christine Rouzioux, Elise Gardiennet, Véronique Avettand-Fenoel, Alice-Andrée Mariaggi, Marine Fillion, Faroudy Boufassa, Pauline Trémeaux, Jean-Christophe Plantier, Adeline Melard, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, 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, Laboratoire de Virologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Codex ANRS cohort study group, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Caen Normandie (UNICAEN), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Epidemiology and Population Health, Epidemiology of HIV and STI Team (U1018 Inserm ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: 0301 basic medicine, Microbiology (medical), HIV rapid screening test, Blotting, Western, HIV diagnosis, Human immunodeficiency virus (HIV), Enzyme-Linked Immunosorbent Assay, HIV Infections, HIV Antibodies, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Serology, Immunoenzyme Techniques, 03 medical and health sciences, Rapid screening test, 0302 clinical medicine, Western blot, medicine, Humans, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Rapid testing, medicine.diagnostic_test, business.industry, HIV, HIV controllers, MESH: ELISA, HIV-1 Western blot, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030112 virology, Virology, 3. Good health, Infectious Diseases, Immunoassay, HIV-2, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ELISA, business, Negative Results
Abstract: Serological assays were performed on 85 human immunodeficiency virus-controller samples . 6% presented a negative rapid screening test 7% presented an indeterminate Western blot. The enzyme immunoassay ratio decreased in controllers who had continual negative ultrasensitive HIV RNA results since inclusion.
Published: 2019

5. Virological response to integrase strand transfer inhibitor-based antiretroviral combinations in HIV-1 group O-infected patients

Author: Jean-Christophe Plantier, Elodie Alessandri-Gradt, Marie Leoz, Guillemette Unal, 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), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène
Subjects: Adult, Male, 0301 basic medicine, Cart, Adolescent, Genotype, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Context (language use), HIV Integrase, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virological response, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, medicine, Humans, Immunology and Allergy, HIV Integrase Inhibitors, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, biology, business.industry, virus diseases, Middle Aged, Viral Load, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, Integrase, Integrase strand transfer inhibitor, Treatment Outcome, 030104 developmental biology, Infectious Diseases, Anti-Retroviral Agents, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Female, Viral hepatitis, business
Abstract: International audience; Although integrase strand transfer inhibitors (INSTIs) are widely used in HIV-1 group M (HIV-1/M) infections, little is known about their efficacy against genetically divergent HIV-1 group O (HIV-1/O) strains. Previous phenotypic works have demonstrated the variable susceptibility of HIV-1/O strains, depending on INSTI drugs. Clinical data are very limited and obtained from a few patients.OBJECTIVES:To investigate the virological success rate of an INSTI-based combination of antiretroviral therapy (cART) in a large population of HIV-1/O-infected patients, and to describe resistance-associated mutations (RAM) at virological failure.METHODS:The virological response of 39 patients receiving INSTI-based cART during their follow-up was analysed i) at the last point of the first INSTI initiation and ii) at their most recent visit. RAM analysis was performed at virological failures. Resistance interpretation was based on the French National Agency of Research on AIDS and viral hepatitis (ANRS) rules.RESULTS:Virological success at both time points of analysis was high, with more than 87% of the patients with undetectable plasma viral load. Among the six patients with virological failure, three selected RAM described for HIV-1/M resistance, and two had already RAM, before INSTI initiation.CONCLUSION:Our results show that HIV-1/O infected patients receiving INSTI-based cART presented a high rate of virological success whatever their previous lines; we have also shown that resistance rules for HIV-1/M could be considered when failure occurs. These data are of importance especially in the context of WHO recommendations for a wider use of this class.
Published: 2019

6. Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

Author: Néant, N. (Nadège), Lingas, G. (Guillaume), Le Hingrat, Q. (Quentin), Ghosn, J. (Jade), Engelmann, I. (Ilka), Lepiller, Q. (Quentin), Gaymard, A. (Alexandre), Ferré, V. (Virginie), Hartard, C. (Cédric), Plantier, J-C. (Jean-Christophe), Thibault, V. (V.), Marlet, J. (Julien), Montes, B. (Brigitte), Bouiller, K. (Kevin), Lescure, F-X. (François-Xavier), Timsit, J-F. (Jean-François), Faure, E. (Emmanuel), Poissy, J. (Julien), Chidiac, C. (Christian), Raffi, F. (François), Kimmoun, A. (Antoine), Etienne, M. (Manuel), Richard, J-C. (Jean-Christophe), Tattevin, P. (Pierre), Garot, D. (Denis), Le Moing, V. (Vincent), Bachelet, D. (Delphine), Tardivon, C. (Coralie), Duval, X. (Xavier), Yazdanpanah, Y. (Yazdan), Mentré, F. (France), Laouénan, C. (Cédric), Visseaux, B. (Benoit), Guedj, J. (Jérémie), plantier, 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, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Pontchaillou [Rennes], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service d'anesthésie - réanimation chirurgicale [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)-Université Paris Cité (UPCité), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Lyon] (hôpital de la Croix-Rousse), Hôpital de la Croix-Rousse [CHU Lyon], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [Hôpital Charles Nicolle, Rouen], Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), ARN régulateurs bactériens et médecine (BRM), 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 ), Service de Médecine Intensive et Réanimation [Tours], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Département d’Epidémiologie, de Biostatistique et de Recherche Clinique [AP-HP Hôpital Bichat - Claude Bernard] (DEBRC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), The study has received financial support from the National Research Agency (ANR) through the ANR-Flash call for COVID-19 (Grant ANR-20-COVI-0018) and the Bill and Melinda Gates Foundation under Grant Agreement INV-017335. The French cohort was supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The funders had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication., ANR-20-COVI-0018,TheraCoV,Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales(2020), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), HAL UR1, Admin, Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales - - TheraCoV2020 - ANR-20-COVI-0018 - COVID-19 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lille, CNRS, Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)], Pathogenèse virale du diabète de type 1 - ULR 3610, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) [CEF2P / CARCINO], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], Centre hospitalier universitaire de Nantes [CHU Nantes], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement [LCPME], Morphogénèse et antigénicité du VIH et du virus des Hépatites [MAVIVH - U1259 Inserm - CHRU Tours ], CHU Montpellier, Laboratoire Chrono-environnement (UMR 6249) [LCE], Service des maladies infectieuses et tropicales, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Centre d’Investigation Clinique de Nantes [CIC Nantes], Défaillance Cardiovasculaire Aiguë et Chronique [DCAC], Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] [INI-CRCT], French-Clinical Research Infrastructure Network - F-CRIN [Paris] [Cardiovascular & Renal Clinical Trialists - CRCT ], Service des maladies infectieuses et tropicales [Rouen], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé [CREATIS], ARN régulateurs bactériens et médecine [BRM], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], Département d'épidémiologie, biostatistique et recherche clinique, and Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]
Subjects: Male, 0301 basic medicine, Medical Sciences, viruses, MESH: Hospitalization, Antibodies, Viral, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Nasopharynx, Epidemiology, MESH: COVID-19, Prospective Studies, 030212 general & internal medicine, MESH: Models, Theoretical, Prospective cohort study, MESH: Aged, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, MESH: Kinetics, Mortality rate, Biological Sciences, Viral Load, Prognosis, viral dynamics, 3. Good health, Hospitalization, Survival Rate, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: RNA, Viral, Cohort, RNA, Viral, Female, France, MESH: Viral Load, Viral load, medicine.medical_specialty, MESH: Survival Rate, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, MESH: Prognosis, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: SARS-CoV-2, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Survival rate, Aged, MESH: Humans, SARS-CoV-2, business.industry, COVID-19, Models, Theoretical, mortality, MESH: Male, MESH: Nasopharynx, MESH: Prospective Studies, MESH: France, Kinetics, 030104 developmental biology, business, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Significance A detailed characterization of viral load kinetics and its association with disease evolution is key to understand the virus pathogenesis, identify high-risk patients, and design better treatment strategies. We here analyze the mortality and the virological information collected in 655 hospitalized patients, including 284 with longitudinal measurements, and we build a mathematical model of virus dynamics and survival. We predict that peak viral load occurs 1 d before symptom onset, on average, and that dynamics of decline after peak is slower in older patients. Viral load dynamics after hospital admission is an independent predictor of the risk of death, suggesting that prolonged viral shedding of high quantities of virus is associated with poor outcome in this population., The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age
Published: 2021

7. Lack of association between chilblains outbreak and severe acute respiratory syndrome coronavirus 2: Histologic and serologic findings from a new immunoassay

Author: Vivien Hébert, Fabienne Jouen, Anne Bénédicte Duval-Modeste, Olivier Boyer, Laurent Drouot, Lucie Cellier, Benoit Veber, Pascal Joly, Véronique Lemée, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-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, Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and CCSD, Accord Elsevier
Subjects: Adult, Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Pneumonia, Viral, Dermatology, Article, Serology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Betacoronavirus, Young Adult, 0302 clinical medicine, COVID-19 Testing, Bias, medicine, Humans, 030212 general & internal medicine, Chilblains, Pandemics, Skin, Immunoassay, medicine.diagnostic_test, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, Outbreak, COVID-19, medicine.disease, [SDV] Life Sciences [q-bio], Pneumonia, Immunology, Female, business, Coronavirus Infections
Published: 2020

8. HIV-1 non-group M phenotypic susceptibility to integrase strand transfer inhibitors

Author: Diane Descamps, Guillemette Unal, Mélanie Bertine, Charlotte Charpentier, Elodie Alessandri-Gradt, Gilles Collin, Marie Leoz, Jean-Christophe Plantier, A. Tourneroche, 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, 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, HIV Infections, HIV Integrase, Drug resistance, Quinolones, Piperazines, polymorphism, chemistry.chemical_compound, Genotype, Pharmacology (medical), Transfer technique, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Phylogeny, Genetics, Elvitegravir, Phenotype, dolutegravir, 3. Good health, Integrase, Infectious Diseases, transfer technique, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Dolutegravir, elvitegravir, raltegravir, Heterocyclic Compounds, 3-Ring, medicine.drug, Microbiology (medical), Pyridones, 030106 microbiology, Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Inhibitory Concentration 50, 03 medical and health sciences, Raltegravir Potassium, Drug Resistance, Viral, Oxazines, medicine, Humans, HIV Integrase Inhibitors, Pharmacology, Polymorphism, Genetic, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030112 virology, Amino Acid Substitution, chemistry, Mutation, HIV-1, biology.protein, integrase
Abstract: International audience; ObjectivesTo determine natural phenotypic susceptibility of non-group M HIV-1 to integrase strand transfer inhibitors (INSTIs) in a large panel of 39 clinical strains from groups O, N and P and to identify genotypic polymorphisms according to susceptibility levels.MethodsSusceptibility to raltegravir, elvitegravir and dolutegravir was evaluated in 36 HIV-1/O, 2 HIV-1/N and 1 HIV-1/P strains plus an HIV-1/M reference strain. IC50 values were determined after 3 days, and fold changes (FCs) were calculated relative to the HIV-1/M strain. Genotypic polymorphism was determined by amplification of codons 19–263 of the integrase; the natural occurrence of resistance-associated mutations was analysed using the main resistance algorithms and the IAS-USA list. VESPA analysis of the strain sequences was used to determine a signature pattern associated with higher FC.ResultsSimilar IC50 results were observed for the three drugs. Based on the value for the HIV-1/M reference strain, the data showed FC values 10 for six strains (15%). Analysis of the non-M integrase sequences showed a high level of polymorphism without a major genotypic impact; it also revealed mutations that may be associated with the highest FC values obtained for elvitegravir.ConclusionsOur phenotypic data showed that non-M strains are globally susceptible to the three currently used INSTIs, but the impact of the high FC values observed for some strains with elvitegravir needs to be explored. Clinical data are now needed to confirm these phenotypic results.
Published: 2017

9. Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C

Author: Fabien Taieb, Amandine Pisoni, Roxane Schaub, Alain Makinson, Philippe Van de Perre, Jean-Christophe Plantier, Esther Nina Ontsira Ngoyi, Edouard Tuaillon, Karine Bollore, Dramane Kania, Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), 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), Boutin, Marion, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Microbiology (medical), medicine.medical_specialty, diagnosis, Mini Review, Hepatitis C virus, [SDV]Life Sciences [q-bio], lcsh:QR1-502, Human immunodeficiency virus (HIV), medicine.disease_cause, Microbiology, lcsh:Microbiology, 03 medical and health sciences, medicine, Intensive care medicine, Genotyping, 030304 developmental biology, Hepatitis B virus, 0303 health sciences, 030306 microbiology, business.industry, HIV, Viral hepatitis b, Hepatitis C, Hepatitis B, medicine.disease, dried blood spot, 3. Good health, Dried blood spot, [SDV] Life Sciences [q-bio], hard-to-reach population, hepatitis B, hepatitis C, business
Abstract: International audience; Blood collected and dried on a paper card - dried blood spot (DBS) - knows a growing interest as a sampling method that can be performed outside care facilities by capillary puncture, and transported in a simple and safe manner by mail. The benefits of this method for blood collection and transport has recently led the World Health Organization to recommend DBS for HIV and hepatitis B and C diagnosis. The clinical utility of DBS sampling to improve diagnostics and care of HIV and hepatitis B and C infection in hard to reach populations, key populations and people living in low-income settings was highlighted. Literature about usefulness of DBS specimens in the therapeutic cascade of care - screening, confirmation, quantification of nucleic acids, and resistance genotyping -, was reviewed. DBS samples are suitable for testing antibodies, antigens, or nucleic acids using most laboratory methods. Good sensibility and specificity have been reported for infant HIV diagnosis and diagnosis of hepatitis B and C. The performance of HIV RNA testing on DBS to identified virological failure on antiretroviral therapy is also high but not optimal because of the dilution of dried blood in the elution buffer, reducing the analytical sensitivity, and because of the contamination by intracellular HIV DNA. Standardized protocols are needed for inter-laboratory comparisons, and manufacturers should pursue regulatory approval for in vitro diagnostics using DBS specimens. Despite these limitations, DBS sampling is a clinically relevant tool to improve access to infectious disease diagnosis worldwide.
Published: 2019

10. 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

11. Comparative Immunovirological and Clinical Responses to Antiretroviral Therapy Between HIV-1 Group O and HIV-1 Group M Infected Patients

Author: Kouanfack, Charles, Unal, Guillemette, Schaeffer, Laura, Kfutwah, Anfumbom, Aghokeng, Avelin, Mougnutou, Rose, Tchemgui-Noumsi, Nathalie, Alessandri-Gradt, Elodie, Delaporte, Eric, Simon, Francois, Vray, Muriel, Plantier, Jean-Christophe, Alima, Michèle, Essengué, Lucie, Mounpou, Georges, Ngang, Peter, Ngoma, Pauline, Omgba, Vincent, Omam, Deborah, Tonfack, Léonie, Zé, Flore, Akongnwi, Emmanuel, Dumortier, Jérôme, Ngoupo, Paul-Alain, Njouom, Richard, Rousset, Dominique, Vessière, Aurélia, Fouler, Lenaig Le, Madec, Yoann, Bodelet, Marine, Dupre, Jean-Michel, Pavie, Juliette, Rekacewicz, Claire, Garcia, Paula, Colin, Géraldine, Hôpital Central de Yaoundé [Yaoundé], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), DynaMo study group, Institut Pasteur [Paris] (IP), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Microbiology (medical), Cart, medicine.medical_specialty, Anti-HIV Agents, immuno-virological response, 030106 microbiology, HIV-1 group O, Human immunodeficiency virus (HIV), HIV Infections, cART, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Gastroenterology, immunovirological response, 03 medical and health sciences, Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Clinical endpoint, Humans, Protease inhibitor (pharmacology), [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Ritonavir, business.industry, virus diseases, genetic diversity, Viral Load, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Antiretroviral therapy, Pathophysiology, CD4 Lymphocyte Count, 3. Good health, Clinical trial, 030104 developmental biology, Infectious Diseases, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, MESH: HIV-1 group O, Drug Therapy, Combination, Panton–Valentine leukocidin, business
Abstract: BackgroundLittle is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence.MethodsWe performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96.ResultsForty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline.ConclusionsOur data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed.Clinical Trials RegistrationNCT00658346.
Published: 2019

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

Author: Constance Delaugerre, Virginie Ferré, Anne Maillard, Vincent Calvez, Audrey Mirand, Anne-Geneviève Marcelin, Corinne Amiel, Julia Dina, Coralie Pallier, Hélène Le Guillou-Guillemette, Stéphanie Raymond, D. B. Fofana, Thomas Mourez, Hélène Jeulin, Samira Fafi-Kremer, Brigitte Montes, Pantxika Bellecave, Sophie Vallet, Thuy Van Nguyen, Diane Descamps, Catherine Roussel, Maxime Grude, Mary-Anne Trabaud, Charlotte Charpentier, Laurence Bocket, Philippe Flandre, Laura Le Guen, Anne Signori-Schmuck, Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Toulouse [Toulouse], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Simulation et Traitement de l'information pour l'Exploitation des systèmes de Production (EDF R&D STEP), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Microbiologie Fondamentale et Pathogénicité (MFP), Service de virologie et unité de surveillance biologique [Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Clermont-Ferrand, CHU Lille, CHU Saint-Antoine [AP-HP], Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Saint Eloi (CHRU Montpellier), Service de Virologie [CHRU Nancy], CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Caen Normandie (UNICAEN), Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Saint-Eloi, Mzembaba, Sandy, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, MESH: Sequence Analysis, DNA, MESH: Treatment Failure, Aucun, Integrase inhibitor, HIV Infections, Drug resistance, MESH: HIV Seropositivity / drug therapy, MESH: Genotype, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, HIV Seropositivity, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Middle Aged, biology, Elvitegravir, Middle Aged, Viral Load, 3. Good health, Integrase, MESH: HIV-1 / genetics, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Viral load, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Mutation, Genotype, MESH: HIV Integrase Inhibitors / therapeutic use, 030106 microbiology, MESH: HIV Infections / drug therapy, MESH: Drug Resistance, Multiple, Viral / genetics, MESH: HIV-1 / drug effects, 03 medical and health sciences, Drug Resistance, Multiple, Viral, Internal medicine, medicine, Humans, HIV Integrase Inhibitors, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, MESH: Viral Load / drug effects, MESH: Humans, business.industry, MESH: Adult, Sequence Analysis, DNA, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Regimen, chemistry, Mutation, HIV-1, biology.protein, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, MESH: Female
Abstract: International audience; Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
Published: 2019

13. Evaluation of four commercial extraction-quantification systems to monitor EBV or CMV viral load in whole blood

Author: Adeline Baron, Albane Gicquel, Marie Gueudin, Jean-Christophe Plantier, Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène
Subjects: 0301 basic medicine, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Early introduction, Serial dilution, [SDV]Life Sciences [q-bio], 030106 microbiology, Cytomegalovirus, 03 medical and health sciences, 0302 clinical medicine, Limit of Detection, Virology, Humans, Medicine, 030212 general & internal medicine, Whole blood, business.industry, Reproducibility of Results, Viral Load, 3. Good health, Infectious Diseases, Cytomegalovirus Infections, DNA, Viral, Reagent Kits, Diagnostic, business, Viral load
Abstract: Background Measurement of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viral loads is commonly used to monitor posttransplant patients. Two new systems (eMAG/eSTREAM and Versant/kPCR) have been recently commercialized. Objectives To evaluate the performance of four systems to quantify CMV and EBV in whole blood. Study design Three extraction and real-time PCR amplification systems: m2000SP/RT (M2000), eMAG/eSTREAM (EMAG), and Versant/kPCR (KPCR) were compared with our routine system Qiasymphony/RGQ (QS/RGQ). The 4 systems were tested using 3 dilutions in triplicate according to the WHO international standard (WHO-IS) for intra-assay reproducibility; 56 whole blood samples (24 patients, 4 follow-ups) for CMV and 45 samples (27 patients, 3 follow-ups) for EBV. Results For CMV, the mean of the WHO-IS (expected value: 4.7 Log IU/ml) was: QS/RGQ=4.84, M2000=4.61, EMAG=4.33, and KPCR=4.79. One patient (10 samples) presented a major underquantification by QS/RGQ. Of the 46 remaining samples, 41 were quantified with QS/RGQ, 43 with M2000, 33 with EMAG and 24 with KPCR. For EBV, the mean of the WHO-IS was: QS/RGQ=4.70, M2000=4.61, EMAG=4.62, and KPCR=4.57. Among the 45 samples, 43 were quantified with QS/RGQ, 39 with M2000, 40 with EMAG and 32 with KPCR. Conclusion The results obtained with the WHO-IS were very good. The results of patients' samples were well correlated with the announced sensitivity of each system. The elevated threshold of the KPCR CMV assay may be problematic for the follow-up of highly immunocompromised patients who require early introduction of treatment.
Published: 2019

14. Évolution des VIH-1 groupes M et O : analyse génétique comparée de 20 formes recombinantes VIH-1 inter-groupes

Author: Moisan, Alice, de Oliveira, Fabienne, Cappy, Pierre, Ngoupo, Paul-Alain, Vessière, Aurelia, Lemée, Veronique, Mourez, Thomas, Alessandri-Gradt, Elodie, Plantier, Jean-Christophe, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), and Mzembaba, Sandy
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

15. Mise en évidence d'une co-infection VIH-1/M+O par l'émergence in vivo d'un recombinant VIH-1/MO

Author: Moisan, Alice, de Oliveira, Fabienne, Pronier, Charlotte, Chapplain, Jean-Marc, Tremeaux, Pauline, Cappy, Pierre, Lemée, Veronique, Maillard, Anne, Plantier, Jean-Christophe, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Pontchaillou [Rennes], Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [Rennes] = Virology [Rennes], Mzembaba, Sandy, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Service des maladies infectieuses et réanimation médicale [Rennes], Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Laboratoire de Virologie [CHU Rennes]
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

16. Comparative performance of the Biocentric Generic Viral Load, Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and m2000 Abbott assays for quantifying HIV-1 B and non-B strains: Underestimation of some CRF02 strains

Author: M Gousset, Adeline Mélard, Marie Gueudin, Marie-Laure Chaix, Laurence Meyer, N. Lerolle, Julia Dina, Jean-Paul Viard, Jean-Christophe Plantier, Véronique Avettand-Fenoel, Christine Rouzioux, Anne Maillard, Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Laboratoire de Virologie CHU de Rennes, Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de recherche en épidémiologie et santé des populations (CESP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Laboratoire de Virologie [Rennes] = Virology [Rennes], CHU Pontchaillou [Rennes], 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: 0301 basic medicine, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Sensitivity and Specificity, World health, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Genetic Evolution, Virology, HIV Seropositivity, medicine, Humans, Mass Screening, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Plasma samples, Clinical Laboratory Techniques, Viral Load, Antiretroviral therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological surveillance, HIV-1, RNA, Viral, France, Viral load
Abstract: Background HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). Objectives The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. Study design The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. Results We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. Conclusions These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.
Published: 2019

17. Performances des trousses Panther/Fusion virus respiratoires (Hologic) chez les enfants de moins de 3 ans

Author: Baron, Adeline, Mirand, Audrey, Vabret, Astrid, Plantier, Jean, Gueudin, Marie, 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, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

18. Impact of natural polymorphisms of HIV-1 non-group M on genotypic susceptibility to the attachment inhibitor fostemsavir

Author: Jean-Christophe Plantier, Diane Descamps, Marie Leoz, Charlotte Charpentier, Elodie Alessandri-Gradt, Thomas Mourez, 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, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Mzembaba, Sandy
Subjects: CD4-Positive T-Lymphocytes, 0301 basic medicine, Microbiology (medical), Anti-HIV Agents, phenotype, genotype, 030106 microbiology, Human immunodeficiency virus (HIV), Virus Attachment, HIV Infections, hiv, hiv-1, Drug resistance, Biology, [SDV.MP.PRO] Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Piperazines, polymorphism, 03 medical and health sciences, Phylogenetics, Drug Resistance, Viral, Genotype, medicine, Genetic predisposition, Humans, Pharmacology (medical), genetics, viruses, fostemsavir, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Pharmacology, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetic diversity, Polymorphism, Genetic, hiv envelope protein gp120, Phenotype, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, immunity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Organophosphates, 3. Good health, 030104 developmental biology, Infectious Diseases, Fostemsavir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Background:Fostemsavir belongs to the new class of attachment inhibitors (AIs); it inhibits the entry of HIV into CD4+ T-lymphocytes by blocking conformational changes in gp120. This is a promising AI, but previous phenotypic data showed that genetically divergent HIV-1 group O could present natural resistance to this drug. These data were obtained from only two strains, which are not representative of the high intra-group genetic diversity. Moreover, no data are available concerning the other divergent HIV-1 groups (N and P).Objectives:To further investigate the natural genotypic susceptibility of HIV-1 groups O, N and P (HIV-1 non-M) to fostemsavir, using a large set of sequences.Methods:The frequency of eight substitutions associated with decreased susceptibility to fostemsavir (L116P, A204D, S375M/H, M426L, M434I, M475I and V506M), was investigated in 111 gp120 sequences from groups O (n = 100), N (n = 9) and P (n = 2).Results:All HIV-1 group N sequences harboured the three substitutions S375M, M426L and M434I, whereas only 1% and 10% of HIV-1 group O sequences harboured the S375H + M426L and S375H + M434I patterns, respectively. The main genetic profile of HIV-1 groups P and O combined S375H with two atypical substitutions (M426S and M434L). Five group O sequences did not display any of the eight substitutions, but had atypical residues with unknown impact.Conclusions:The genetic polymorphisms in the gp120 of HIV-1 non-M viruses support the hypothesis that these viruses could largely be resistant to inhibition by fostemsavir. Only 5% of group O strains could display full genetic susceptibility. Extensive phenotypic studies are now required.
Published: 2018

19. Analyse des régions LTR du génome d'un VIH-1 recombinant inter-groupes M et O : étude de l'émergence des points de cassure et caractérisation des différentes populations

Author: Moisan, Alice, Caron, Juliette, de Oliveira, Fabienne, Plantier, Jean-Christophe, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Mzembaba, Sandy
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

20. Mise au point d'une méthode de quantification de l'ARN plasmatique spécifique des VIH-1 de groupe M

Author: Gicquel, Albane, Lemée, Veronique, Gueudin, Marie, Alessandri-Gradt, Elodie, Plantier, Jean-Christophe, Moisan, Alice, 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], Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Mzembaba, Sandy
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS, [SDV.BIO] Life Sciences [q-bio]/Biotechnology
Abstract: International audience
Published: 2018

21. 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

22. Short Communication: Characterization of a New HIV-1 Group N Isolate Originating from a Cameroonian Patient

Author: Elodie Téclaire Ngo-Malabo, Jean-Christophe Plantier, Anfumbom Kfutwah, Laure Ngono, Paul Alain Ngoupo, Fabienne De Oliveira, Serge Alain Sadeuh-Mba, Richard Njouom, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), 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), and Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène
Subjects: Adult, Genotype, HIV-1 group N, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Genome, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, 0302 clinical medicine, Virus strain, Virology, medicine, Humans, 030212 general & internal medicine, Cameroon, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Whole Genome Sequencing, virus diseases, HIV screening, tetherin, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Amino acid, Infectious Diseases, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Tetherin, HIV-1, Female, Vpu protein, epidemiology, Antagonism
Abstract: International audience; HIV-1 group N (HIV-1/N) remains rare and mainly restricted to Cameroon. In this study, we report a new HIV-1/N infected case identified during routine HIV screening activities in Yaounde. The genetic characterization of the near full-length genome of this virus strain revealed that it is genetically distinct to all HIV-1/N described to date. However, the Vpu protein responsible for tetherin antagonism displayed the same amino acid substitutions (E15A, V19A, I25L, and V26L) as other HIV-1/N from Cameroon.
Published: 2018

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

Author: Alexandre Storto, Diane Descamps, Anne Maillard, Audrey Mirand, Corinne Amiel, Charlotte Charpentier, Vincent Calvez, Thuy Van Nguyen, Laurence Bocket, Coralie Pallier, Audrey Rodallec, Elisabeth André-Garnier, Marie Leoz, Laurence Morand-Joubert, Isabelle Malet, Stéphanie Raymond, Véronique Schneider, Catherine Roussel, Camille Tumiotto, Constance Delaugerre, Anne-Geneviève Marcelin, Julia Dina, Jean-Christophe Plantier, Brigitte Montes, Anne Signori-Schmuck, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu de Nantes, Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Virologie [Villejuif], Hôpital Paul Brousse, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Tenon [APHP], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Microbiology (medical), Genotype, 030106 microbiology, Mutation, Missense, Integrase inhibitor, HIV Infections, HIV Integrase, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, 03 medical and health sciences, chemistry.chemical_compound, Gene Frequency, medicine, Prevalence, Humans, Pharmacology (medical), HIV Integrase Inhibitors, Pharmacology, biology, Elvitegravir, business.industry, Viral Load, Raltegravir, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Integrase, Regimen, Infectious Diseases, Treatment Outcome, chemistry, Dolutegravir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, France, business, Viral load, medicine.drug
Abstract: International audience; ObjectivesTo assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.MethodsThis was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.ResultsPrevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL
Published: 2018

24. HIV-1 group P infection: towards a dead-end infection?

Author: Elodie Alessandri-Gradt, David Robertson, Paul-Alain Ngoupo, Philippe Mauclère, Fabienne De Oliveira, Jean-Christophe Plantier, François Simon, Marie Leoz, Felix Feyertag, Véronique Lemée, 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, Faculty of Life Sciences [Manchester], University of Manchester [Manchester], MRC - University of Glasgow Centre for Virus Research, University of Nevada [Reno], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Ravinala conseil, 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), Université Paris Diderot - Paris 7 (UPD7), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: 0301 basic medicine, Serotype, Virus Cultivation, Genotype, Genotyping Techniques, Immunology, Human immunodeficiency virus (HIV), Adaptation, Biological, Mutation, Missense, Virulence, HIV Infections, Biology, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, gag Gene Products, Human Immunodeficiency Virus, 03 medical and health sciences, Dead end, medicine, Immunology and Allergy, Humans, Prospective Studies, Serotyping, MESH: Adaptation, Biological, Blood/virology, CD4 Lymphocyte Count, HIV Infections/pathology, HIV Infections/virology, HIV-1/classification, HIV-1/genetics, HIV-1/isolation & purification, HIV-1/pathogenicity, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cells, Cultured, Follow up studies, virus diseases, Viral Load, 030112 virology, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Blood, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Leukocytes, Mononuclear, Viral load, Follow-Up Studies
Abstract: International audience; OBJECTIVES:HIV/1 group P (HIV-1/P) is the last HIV/1 group discovered and, to date, constitutes only two strains. To obtain new insight into this divergent group, we screened for new infections by developing specific tools, and analysed phenotypic and genotypic properties of the prototypic strain RBF168. In addition, the follow-up of the unique infected patient monitored so far has raised the knowledge of the natural history of this infection and its therapeutic management.DESIGN/METHODS:We developed an HIV-1/P specific seromolecular strategy and screened over 29 498 specimen samples. Infectivity and evolution of the gag-30 position, considered as marker of adaptation to human, were explored by successive passages of RBF168 strain onto human peripheral blood mononuclear cells. Natural history and immunovirological responses to combined antiretroviral therapy (cART) were analysed based on CD4+ cells and plasmatic viral load evolution.RESULTS:No new infection was detected. Infectivity of RBF168 was found lower, relative to other main HIV groups and the conservative methionine found in the gag-30 position revealed a lack of adaptation to human. The follow-up of the patient during the 5-year ART-free period, showed a relative stability of CD4+ cell count with a mean of 326 cells/μl. Initiation of cART led to rapid RNA undetectability with a significant increase of CD4+ cells, reaching 687 cells/μl after 8 years.CONCLUSION:Our results showed that HIV-1/P strains remain extremely rare and could be less adapted and pathogenic than other HIV strains. These data lead to the hypothesis that HIV-1/P infection could evolve towards, or even already corresponds to, a dead-end infection.
Published: 2018

25. What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

Author: Bendenoun, M., Samri, A., Avettand-Fènoël, V., Cardinaud, S., Descours, B., Carcelain, G., Mazeron, M.-C., Bergmann, J.-F., Urrutia, A., Moris, A., Rouzioux, C., Simon, F., Andre, Patrice, Pocard, M., Dray, X., Mourez, T., Vieillard, V., Autran, B., Barin, F., Sellier, P., Service de Médecine Interne [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), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut 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), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de chirurgie digestive et cancérologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Service d'angiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Gastroentérologie [CHU Lariboisière], 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), Centre national de référence du VIH INSERM U966, Université de Tours (UT), Centre d'Immunologie et de Maladies Infectieuses (CIMI), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université de Tours, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de l'intégration, du matériau au système (IMS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Diseases Department, Université Montpellier 1 (UM1), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Immunologie - Immunopathologie - Immunothérapie (I3), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Male, HLA B*07 C*07, T-Lymphocytes, lcsh:Medicine, HIV Infections, HIV-1 DNA, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, ComputingMilieux_MISCELLANEOUS, Phylogeny, lcsh:R5-920, Immune activation, lcsh:R, Homosexuality, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Incomplete western blot, Sexual Partners, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Elite control, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, [SDV.IMM]Life Sciences [q-bio]/Immunology, Partner, lcsh:Medicine (General), Genetic Background
Abstract: International audience; BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay. HIV-DNA was detected at 1.1 and 2 copies/106 PBMCs in 2009 and 2015 respectively, at 1.2 copies/106 cells in rectal cells in 2011. WBs showed weak reactivity with antibodies to gp160, p55 and p25 from 2007 to 2014, remaining incomplete in 2017. CD4 T cells were susceptible to various strains including HIVKON, a primary isolate of his own CRF02_AG variant. CD8 T cells showed a strong poly-functional response against HIV-Gag, producing mainly IFN-γ; a robust capacity of antibody-dependant cell cytotoxicity (ADCC) was observed in NK cells. Case patient was group B KIR haplotype. Neutralizing antibodies were not detected. CD4 and CD8 blood T cells showed normal proportions without increased activation markers. Phylogenetic analyses identified the same CRF02_AG variant in his partner. The patient and his partner were heterozygous for the CCR5ΔD32 deletion and shared HLA-B*07, C*07 non-protective alleles. INTERPRETATION: This thorough description of the natural history of an individual controlling HIV-1 in various compartments for ten years despite lack of protective alleles, and of his partner, may have implications for strategies to cure HIV-1 infection.
Published: 2018

26. Presence of respiratory viruses in ICU patients with community acquired-pneumonia (CAP): a one-year restrospective single center study

Author: Giry, Marion, Misset, Benoit, Boyer, Déborah, Baron, Adeline, Lemée, Ludovic, Plantier, Jean-Christophe, Gueudin, Marie, Mzembaba, Sandy, Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de microbiologie [CHU Rouen], Laboratoire de virologie [Rouen], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

27. 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

28. HIV-1 sequences in the epidemic suggest an alternative pathway for the generation of the Long Terminal Repeats

Author: Pierre Cappy, Alice Moisan, Fabienne De Oliveira, Jean-Christophe Plantier, Matteo Negroni, CHU Rouen, Normandie Université (NU), Laboratoire de virologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Recombination, Genetic, viruses, [SDV]Life Sciences [q-bio], lcsh:R, Terminal Repeat Sequences, lcsh:Medicine, HIV Infections, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Genome, Viral, Article, Evolution, Molecular, HIV-1, Humans, RNA, Viral, lcsh:Q, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:Science, Epidemics, Sequence Analysis, Phylogeny, ComputingMilieux_MISCELLANEOUS
Abstract: To generate the long-terminal repeats (LTR) that border the integrated viral genome, two-strand transfer steps must occur during reverse transcription. Analysis of the genetic polymorphisms that are present in the LTR of HIV-1 heterozygous virions in single infection cycle studies has revealed which of the two copies of genomic RNAs is used for each transfer event. Thus, the first event of strand transfer has been described to be either intra- or intermolecular, while the second event is generally intramolecular. Here, we repeated these analyses using sequences from HIV databases and extended the study to the regions surrounding the LTR. We observed a striking correlation between the pattern of recombination in the LTR and the phylogenetic origin of the surrounding sequences. This correlation suggests that the second-strand transfer can be either intra- or intermolecular and, interestingly, could reflect an effect of proximity between nucleic acids that would guide this transfer. This factor could be particularly relevant for heterozygous viruses containing highly divergent genomic RNAs, such as those considered in the present study.
Published: 2017

29. Interlaboratory quality control of total HIV-1 DNA load measurement for multicenter reservoir studies

Author: Karine Sauné, Jean-Christophe Plantier, Audrey Rodallec, Edouard Tuaillon, Anne Maillard, Véronique Avettand-Fenoel, Christine Rouzioux, Florence Damond, Adeline Mélard, Marie Gueudin, Constance Delaugerre, Pierre Gantner, Julia Dina, Laboratoire de Virologie [Strasbourg], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), 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), 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), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Pontchaillou [Rennes], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de l'Hôtel Dieu [CHU-HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CIC - Toulouse (CIC 1436 - CHU de Toulouse/Inserm/UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Pierre-Paul Riquet [Toulouse], CHU Toulouse [Toulouse], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Quality Control, 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], interlaboratory quality control, Human immunodeficiency virus (HIV), Biology, HIV-1 DNA, Real-Time Polymerase Chain Reaction, Bioinformatics, medicine.disease_cause, 03 medical and health sciences, Virology, Internal medicine, medicine, Humans, Hiv 1 dna, Intersectoral Collaboration, Disease Reservoirs, Reproducibility, Load measurement, Clinical Laboratory Techniques, Reproducibility of Results, Viral Load, quantification, 3. Good health, 030104 developmental biology, Infectious Diseases, DNA, Viral, HIV-1, RNA, Viral
Abstract: Background: Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Methods: Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in 4 samples (QCMD). Results: Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log10 copies/106PBMC) for the three positive QC that were correctly classified by each laboratory (QC1
Published: 2017

30. Massive Iatrogenic Outbreak of Human Immunodeficiency Virus Type 1 in Rural Cambodia, 2014-2015

Author: Chunfu Yang, Sophearot Prak, Laurent Ferradini, Chandara Mom, Gérard Lesage, Catherine Gaudy-Graffin, Jean-Christophe Plantier, Sovatha Mam, Artur Ramos, Chhivun Mean, Marie Leoz, William Killam, Didier Fontenille, Francis Barin, Benjamin Roche, Sreymom Ken, Du-Ping Zheng, Allison Black, Alexandra Kerleguer, Vonthanak Saphonn, Janin Nouhin, François Rouet, Masami Fujita, Trevor Bedford, Charlotte Gautier, Kerya Phon, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Institut de Recherche pour le Développement (IRD), Centre National de la Recherche Scientifique (CNRS), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), 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, 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), World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centers for Disease Control and Prevention [Phnom Penh], Embassy of the United States of America, University of Health Sciences [Phnom-Penh, Cambodia] (UHS), This work was supported by grants from the 5% Initiative Expertise France, the Institut Pasteur International Network, and the French National Agency for Research on AIDS and Viral Hepatitis. This research has been also partially been supported by the President’s Emergency Plan for AIDS Relief through the CDC (cooperative agreement number 3U2GGH000989)., and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Male, Rural Population, Iatrogenic Disease, HIV Infections, medicine.disease_cause, Disease Outbreaks, MESH: HIV-1, chemistry.chemical_compound, 0302 clinical medicine, MESH: Aged, 80 and over, iatrogenic outbreak, MESH: Rural Population, MESH: Child, HBV, 030212 general & internal medicine, MESH: Phylogeny, Child, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Phylogeny, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, Transmission (medicine), virus diseases, Hepatitis C, MESH: HIV Infections, Middle Aged, MESH: Case-Control Studies, MESH: Iatrogenic Disease, MESH: Cambodia/epidemiology, 3. Good health, Infectious Diseases, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HCV, Female, Cambodia, Microbiology (medical), Adult, Adolescent, Hepatitis C virus, Disease cluster, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Article, Injections, 03 medical and health sciences, Young Adult, medicine, MESH: Injections, Humans, Avidity, NS5B, Aged, Hepatitis B virus, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Outbreak, HIV, MESH: Adult, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, 030104 developmental biology, chemistry, Case-Control Studies, HIV-1, business, MESH: Female
Abstract: Background In 2014–2015, 242 individuals aged 2–89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent ( Conclusions Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.
Published: 2017

31. New Highly Sensitive Real-Time PCR Assay for HIV-2 Group A and Group B DNA Quantification

Author: Mélanie Bertine, Marie Gueudin, Véronique Avettand-Fenoel, Adeline Mélard, Florence Damond, Christine Rouzioux, Sophie Matheron, Fidéline Collin, Diane Descamps, Jean-Christophe Plantier, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, 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 de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, Coefficient of variation, 030106 microbiology, HIV Infections, Biology, Real-Time Polymerase Chain Reaction, Group A, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Sensitivity and Specificity, gag Gene Products, Human Immunodeficiency Virus, quantiﬁcation, 03 medical and health sciences, chemistry.chemical_compound, Virology, Humans, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, HIV Long Terminal Repeat, DNA, Middle Aged, Viral Load, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Long terminal repeat, 3. Good health, Real-time polymerase chain reaction, PCR, chemistry, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, DNA, Viral, HIV-2, Nucleic acid, RNA, Viral, Female, Viral load
Abstract: HIV-2 infection is characterized by a very low replication rate in most cases and low progression. This necessitates an approach to patient monitoring that differs from that for HIV-1 infection. Here, a new highly specific and sensitive method for HIV-2 DNA quantification was developed. The new test is based on quantitative real-time PCR targeting the long terminal repeat (LTR) andgagregions and using an internal control. Analytical performance was determined in three laboratories, and clinical performance was determined on blood samples from 63 patients infected with HIV-2 group A (n= 35) or group B (n= 28). The specificity was 100%. The 95% limit of detection was three copies/PCR and the limit of quantification was six copies/PCR. The within-run coefficients of variation were between 1.03% at 3.78 log10copies/PCR and 27.02% at 0.78 log10copies/PCR. The between-run coefficient of variation was 5.10%. Both manual and automated nucleic acid extraction methods were validated. HIV-2 DNA loads were detectable in blood cells from all 63 patients. When HIV-2 DNA was quantifiable, median loads were significantly higher in antiretroviral-treated than in naive patients and were similar for groups A and B. HIV-2 DNA load was correlated with HIV-2 RNA load (r= 0.68; 95% confidence interval [CI], 0.4 to 0.8;P< 0.0001). Our data show that this new assay is highly sensitive and quantifies the two main HIV-2 groups, making it useful for the diagnosis of HIV-2 infection and for pathogenesis studies on HIV-2 reservoirs.
Published: 2017

32. Efficient Vpu-Mediated Tetherin Antagonism by an HIV-1 Group O Strain

Author: Marie Leoz, Frank Kirchhoff, Beatrice H. Hahn, Matthias Geyer, Daniel Sauter, Jean-Christophe Plantier, Christina M. Stürzel, Simon Langer, Gerald H. Learn, Frederic Bibollet-Ruche, Kathrin Starz, Katharina Mack, University of Ulm (UUlm), University of Pennsylvania [Philadelphia], 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], Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and University of Bonn
Subjects: CD4-Positive T-Lymphocytes, 0301 basic medicine, viruses, Human Immunodeficiency Virus Proteins, Immunology, Antigen presentation, HIV-1 group O, GPI-Linked Proteins, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, Cell Line, 03 medical and health sciences, Antigens, CD, Virology, Vpu, Humans, Viral Regulatory and Accessory Proteins, Virus Release, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, NF-kappa B, virus diseases, tetherin, NFKB1, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, antagonism, 3. Good health, Ubiquitin ligase, Cell biology, 030104 developmental biology, Cell culture, Cytoplasm, Insect Science, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, biology.protein, Tetherin, Pathogenesis and Immunity
Abstract: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as a tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion. In this study, we identified an unusual HIV-1 group O strain (RBF206) that evolved Vpu as an effective antagonist of human tetherin. While both RBF206 Vpu and Nef exert anti-tetherin activity in transient-transfection assays, mainly Vpu promotes RBF206 release in infected CD4 + T cells. Although mutations distinct from the adaptive changes observed in group M Vpus (M-Vpus) were critical for the acquisition of its anti-tetherin activity, RBF206 O-Vpu potently suppresses NF-κB activation and reduces CD4 cell surface expression. Interestingly, RBF206 Vpu counteracts tetherin in a largely species-independent manner, degrading both the long and short isoforms of human tetherin. Downmodulation of CD4, but not counteraction of tetherin, by RBF206 Vpu was dependent on the cellular ubiquitin ligase machinery. Our data present the first example of an HIV-1 group O Vpu that efficiently antagonizes human tetherin and suggest that counteraction by O-Nefs may be suboptimal. IMPORTANCE Previous studies showed that HIV-1 groups M and O evolved two alternative strategies to counteract the human ortholog of the restriction factor tetherin. While HIV-1 group M switched from Nef to Vpu due to a deletion in the cytoplasmic domain of human tetherin, HIV-1 group O, which lacks Vpu-mediated anti-tetherin activity, acquired a Nef protein that is able to target a region adjacent to the deletion. Here we report an unusual exception, identifying a strain of HIV-1 group O (RBF206) whose Vpu protein evolved an effective antagonism of human tetherin. Interestingly, the adaptive changes in RBF206 Vpu are distinct from those found in M-Vpus and mediate efficient counteraction of both the long and short isoforms of this restriction factor. Our results further illustrate the enormous flexibility of HIV-1 in counteracting human defense mechanisms.
Published: 2017

33. A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

Author: Elodie Martin, Thomas Mourez, Etienne Brochot, François Helle, Justine Faucher, Sandrine Castelain, Virginie Morel, Gabriel Choukroun, Gilles Duverlie, Catherine François, Aramco Research & Innovation, Centre d'Études Linguistiques - Corpus, Discours et Sociétés (CEL), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Centre de Recherches Interdisciplinaires en Lettres, Langues, Arts et Sciences Humaines [UE6_2] (CRILLASH), Université des Antilles (UA), 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), Unité de Virologie clinique et fondamentale (UVCF), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], CHU Rouen, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Centre de Recherches Interdisciplinaires en Lettres, Langues, Arts et Sciences Humaines (CRILLASH), Institut de biologie de Lille - UMS 3702 (IBL), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: 0301 basic medicine, Microbiology (medical), Genotype, Genotyping Techniques, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, Computational biology, Biology, medicine.disease_cause, Genome, 03 medical and health sciences, Virology, medicine, Humans, Typing, education, Viral Structural Proteins, Polyomavirus Infections, education.field_of_study, Genetic Variation, virus diseases, Sequence Analysis, DNA, Subtyping, BK virus, Transplantation, Tumor Virus Infections, 030104 developmental biology, BK Virus
Abstract: BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases.
Published: 2017

34. Evolution of HIV-1 groups M and O: genetic comparative analysis of 23 HIV-1/MO inter-group recombinant forms

Author: Moisan, Alice, de Oliveira, Fabienne, Cappy, Pierre, Ngoupo, Paul-Alain, Njouom, Richard, Plantier, Jean-Christophe, Mzembaba, Sandy, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Pasteur du Cameroun, and Réseau International des Instituts Pasteur (RIIP)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

35. Performance of 9 rapid diagnostic HIV tests on a wide panel of whole blood samples

Author: Mourez, Thomas, Lemée, Veronique, Delbos, Valérie, Delaugerre, Constance, Etienne, Manuel, Alessandri-Gradt, Elodie, Simon, Francois, Chaix, Marie-Laure, Plantier, Jean-Christophe, Mzembaba, Sandy, 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), Service des maladies infectieuses et tropicales [Rouen], 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), Université Paris Diderot - Paris 7 (UPD7), COREVIH Normandie, and Université de Caen Normandie (UNICAEN)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

36. Analyse et caractérisation des régions LTRs du génome d'un VIH-1 recombinant inter-groupes M et O

Author: CARON, Juliette, Moisan, Alice, de Oliveira, Fabienne, Plantier, Jean-Christophe, Mzembaba, Sandy, 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), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

37. HIV-1 group O resistance pathway with raltegravir is similar to HIV-1 group M

Author: Marjolaine Morgand, Elodie Alessandri-Gradt, François Simon, P. Sellier, Constance Delaugerre, Jean-Christophe Plantier, Gilles Peytavin, 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, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Subjects: 0303 health sciences, 030306 microbiology, Immunology, Human immunodeficiency virus (HIV), Biology, Raltegravir, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Group (periodic table), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, Immunology and Allergy, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, medicine.drug
Abstract: International audience
Published: 2015

38. Multiple HIV-1/M + HIV-1/O dual infections and new HIV-1/MO inter-group recombinant forms detected in Cameroon

Author: Thomas Mourez, Dominique Rousset, Aurélia Vessière, Fabienne De Oliveira, Paul-Alain Ngoupo, Jean-Christophe Plantier, François Simon, Elodie Alessandri-Gradt, Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], 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), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de la Guyane, We thank the Centre Pasteur in Cameroun and Rouen University Hospital for financial support., Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN)
Subjects: 0301 basic medicine, Serotype, Dual infections, Genotype, M and O inter-group recombinant forms, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Serogroup, Serology, law.invention, MESH: Genotype, MESH: HIV-1, 03 medical and health sciences, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, MESH: Molecular Epidemiology, Humans, 030212 general & internal medicine, Cameroon, Prospective Studies, Recombination, Genetic, HIV genetic diversity, Molecular Epidemiology, MESH: Humans, biology, Coinfection, Research, virus diseases, MESH: HIV Infections, MESH: Serogroup, MESH: Prospective Studies, 3. Good health, MESH: Coinfection, 030104 developmental biology, Infectious Diseases, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Recombinant DNA, HIV-1, MESH: Cameroon/epidemiology, MESH: Recombination, Genetic, Antibody
Abstract: International audience; BACKGROUND: Due to the prevalence of HIV-1 group M and the endemicity of HIV-1 group O infections in Cameroon, patients may be infected with both viruses and/or with HIV-1/MO recombinant forms. Such atypical infections may be deleterious in terms of diagnosis and therapeutic management due to the high divergence of HIV-1/O. The aim of this study was to identify prospectively such atypical infections in Cameroon.RESULTS: Based on serological screening by env-V3 serotyping and a molecular strategy using group-specific (RT)-PCRs, we identified 10 Cameroonian patients harboring three different profiles of infection: (1) 4 HIV-1/M + O dual infections without evidence of recombinant; (2) 5 recombinants associated with one or both parental strains; and (3) 1 new recombinant form without parental strains.CONCLUSIONS: This work highlights the dynamic co-evolution of these two HIV groups in Cameroon that could lead to the emergence of a circulating recombinant form MO, and the need for accurate identification of such atypical infections for precise diagnosis, virological monitoring and therapeutic management with adapted tools.
Published: 2016

39. Multi-site clinical evaluation of the Xpert® HIV-1 viral load assay

Author: Kate Templeton, A. H. B. Wu, Jeanne A. Jordan, Jean-Christophe Plantier, The George Washington University (GW), Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Royal Infirmary of Edinburgh, and San Francisco General Hospital Medical Center [San Francisco, CA, USA]
Subjects: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Sensitivity and Specificity, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Specimen Handling, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Virology, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Aged, 80 and over, Plasma samples, business.industry, Multi site, Middle Aged, Viral Load, Antiretroviral therapy, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Treatment Outcome, Specimen collection, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, RNA, Viral, Female, Fresh frozen plasma, business, Clinical evaluation, Viral load
Abstract: The most important reason for measuring HIV-1 viral load (VL) is to monitor the effectiveness of antiretroviral therapy (ART), both for the initial therapeutic response and sustained responses. Maintaining low or undetectable HIV-1 VL levels can reduce both the risks of progression to AIDS and transmission of infection to others.To evaluate the diagnostic accuracy of Xpert(®) HIV-1 Viral Load (VL) assay compared to the Abbott RealTime HIV-1 assay, including assessing specificity by testing plasma specimens from confirmed HIV-1 negative blood donors.Subjects were enrolled from 4 participating sites, 2 in Europe and 2 in the USA. Fresh plasma samples were tested prospectively, while frozen plasma samples were collected prospectively, and tested retrospectively after selection of specimens to cover the assay's quantification range (40cp/mL-10,000,000 cp/mL). Eligibility criteria included a clinician ordered HIV-1 VL test from a confirmed HIV-1 positive adult (≥18 years) with a known antiviral treatment status. Exclusion criteria included previous enrollment in this study or improper specimen collection. Human blood donor specimens determined to be HIV-1 negative by standard blood bank antibody and nucleic acid amplification methods were used to assess specificity.Of the 764 specimens collected, 752 were eligible for inclusion but 5 were not tested by the Xpert, leaving 747 specimens tested (28.2% from females and 71.8% from males). Valid results were obtained for 724/747 (96.9%) specimens tested using the Xpert HIV-1 VL assay. The Xpert HIV-1 VL assay detected or quantified 568/724 (78.5%) specimens, while the RealTime HIV-1 assay detected or quantified 559/724 (77.2%). Of the 724 specimens tested by both assays, 390 were quantified by both assays and showed strong correlation: r=0.9847, with an R(2)=0.9696. Bland-Altman analysis showed good agreement between the two assays (381/390; 97.7%) with a distribution within 0.5 log10 cp/mL centered around zero. Xpert yielded VLs for 393 (80%) of the 494 quantifiable samples by Abbott. VLs of those specimens quantified by one of the assays, and either detected but not quantified or not detected by the other assay were all170cp/mL. Specificity of the Xpert assay was found to be 100% (109/109), 95% CI: 96.7-100.0.Very good correlation was seen between the Xpert HIV-1 VL and Abbott RealTime HIV-1 assays, with added benefits for Xpert HIV-1 VL of: (1) lot-to-lot consistency traceable to WHO International Standard, (2) requiring both high and low level internal controls to be in range to have a valid result, (3) use of a single HIV-1 target for PCR and (4) faster turn-around-time for results, no need to wait to do batch testing of specimens. In summary, Xpert HIV-1 VL generated accurate VL results that if implemented could allow for actionable and timely treatment decisions during the same clinic visit. This scenario could reduce the loss to follow up often seen when these test results take days to weeks to become available to the clinician and patient.
Published: 2016

40. HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs

Author: Denis M. Tebit, Hamish Patel, Jean-Christophe Plantier, Annette N. Ratcliff, Joseph Liu, Eric J. Arts, Crystal Carpenter, Elodie Alessandri, Case Western Reserve University [Cleveland], 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, 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), and Normandie Université (NU)
Subjects: 0301 basic medicine, Genotype, 030106 microbiology, Immunology, Etravirine, Drug resistance, Microbial Sensitivity Tests, Pharmacology, Virus Replication, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, chemistry.chemical_compound, Inhibitory Concentration 50, Preclinical Studies/Drug Development, Virology, Drug Resistance, Viral, medicine, Humans, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cells, Cultured, Phylogeny, Maraviroc, Polymorphism, Genetic, biology, Elvitegravir, virus diseases, Sequence Analysis, DNA, Raltegravir, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, 3. Good health, Integrase, 030104 developmental biology, Infectious Diseases, Phenotype, chemistry, Anti-Retroviral Agents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, HIV-1, medicine.drug
Abstract: Despite only 30,000 group O HIV-1 infections, a similar genetic diversity is observed among the O subgroups H (head) and T (tail) (previously described as subtypes A, B) as in the 9 group M subtypes (A-K). Group O isolates bearing a cysteine at reverse transcriptase (RT) position 181, predominantly the H strains are intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, their susceptibility to newer antiretroviral drugs such as etravirine, maraviroc, raltegravir (RAL), and elvitegravir (EVG) remains relatively unknown. We tested a large collection of HIV-1 group O strains for their susceptibility to four classes of antiretroviral drugs namely nucleoside RT, non-nucleoside RT, integrase, and entry inhibitors knowing in advance the intrinsic resistance to NNRTIs. Drug target regions were sequenced to determine various polymorphisms and were phylogenetically analyzed. Replication kinetics and fitness assays were performed in U87-CD4(+)CCR5 and CXCR4 cells and peripheral blood mononuclear cells. With all antiretroviral drugs, group O HIV-1 showed higher variability in IC50 values than group M HIV-1. The mean IC50 values for entry and nucleoside reverse transcriptase inhibitor (NRTI) were similar for group O and M HIV-1 isolates. Despite similar susceptibility to maraviroc, the various phenotypic algorithms failed to predict CXCR4 usage based on the V3 Env sequences of group O HIV-1 isolates. Decreased sensitivity of group O HIV-1 to integrase or NNRTIs had no relation to replicative fitness. Group O HIV-1 isolates were 10-fold less sensitive to EVG inhibition than group M HIV-1. These findings suggest that in regions where HIV-1 group O is endemic, first line treatment regimens combining two NRTIs with RAL may provide more sustained virologic responses than the standard regimens involving an NNRTI or protease inhibitors.
Published: 2016

41. Estimation of HIV-1 DNA Level Interfering with Reliability of HIV-1 RNA Quantification Performed on Dried Blood Spots Collected from Successfully Treated Patients

Author: Lassana Sangaré, Armen Sanosyan, Jean-Christophe Plantier, Makoura Barro, François Rouet, Karine Bollore, Christine Rouzioux, Thérèse Kagoné, Abdoul Salam Ouedraogo, Boubacar Nacro, Dramane Kania, Sylvie Zida, Arnaud Kwimatouo Lekpa Franchard, Nicolas Meda, Edouard Tuaillon, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Centre Hospitalier Universitaire Yalgado Ouédraogo (CHUYO), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )
Subjects: 0301 basic medicine, Microbiology (medical), 030106 microbiology, HIV Infections, Biology, Peripheral blood mononuclear cell, Hiv 1 rna, Specimen Handling, 03 medical and health sciences, chemistry.chemical_compound, Virology, Humans, False Positive Reactions, Desiccation, Diagnostic Errors, Dried blood, Hiv 1 dna, Spots, RNA, virus diseases, Viral Load, Molecular biology, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, DNA, Viral, HIV-1, RNA, Viral, Drug Monitoring, Viral load, DNA
Abstract: The impact of HIV-1 DNA coamplification during HIV-1 RNA quantification on dried blood spots (DBS) was explored. False-positive HIV RNA detection (22/62, 35%) was associated with high HIV-1 DNA levels. Specificity of HIV-1 RNA assays on DBS should be evaluated following manufacturer protocols on samples with HIV-1 DNA levels of ≥1,000 copies/10 6 peripheral blood mononuclear cells.
Published: 2016

42. A Multiplex PCR Approach for Detecting Dual Infections and Recombinants Involving Major HIV Variants

Author: Marie Gueudin, Pierre Cappy, Elodie Alessandri-Gradt, Jean-Christophe Plantier, Fabienne De Oliveira, Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)
Subjects: 0301 basic medicine, Microbiology (medical), HIV Infections, Genome, Sensitivity and Specificity, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, chemistry.chemical_compound, Virology, Multiplex polymerase chain reaction, medicine, Humans, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, Strain (chemistry), Coinfection, RNA, virus diseases, HIV, medicine.disease, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, 3. Good health, Integrase, 030104 developmental biology, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Multiplex Polymerase Chain Reaction, DNA
Abstract: The cocirculation of different HIV types and groups can lead to dual infections and recombinants, which hinder diagnosis and therapeutic management. We designed two multiplex PCRs (mPCRs) coupled with capillary electrophoresis to facilitate the detection of such infections. The first, M MO2 , targets three variants (HIV-1/M, HIV-1/O, and HIV-2), and the second, M MO , targets HIV-1/M and HIV-1/O. These mPCRs were validated on DNA and RNA extracts from 19 HIV-1/M, 12 HIV-1/O, and 13 HIV-2 cultures and from mixtures simulating dual infections. They were then assessed with DNA and RNA extracts from samples of 47 clinical monoinfections and HIV-1/M+O dual infections or infections with HIV-1/MO recombinants. Both mPCRs had excellent specificity. Sensitivities ranged from 80 to 100% for in vitro samples and from 58 to 100% for clinical samples, with the results obtained depending on the material used and the region of the genome concerned. Sensitivity was generally lower for DNA than for RNA and for amplifications of the integrase and matrix regions. In terms of global detection (at least one target gene for each strain), both mPCRs yielded a detection rate of 100% for in vitro samples. M MO2 detected 100% of the clinical strains from DNA and 97% from RNA, whereas M MO detected 100% of the strains from both materials. Thus, for in vitro and clinical samples, M MO2 was a useful tool for detecting dual infections with HIV-1 and HIV-2 (referred to as HIV-1+HIV-2) and HIV-1/M+O, and M MO was useful for detecting both MO dual infections and MO mosaic patterns.
Published: 2016

43. Next Generation Sequencing Analysis of HIV-1 Group O Reverse Transcriptase Residue 181C Prevalence and Evolution over Time, With or Without Antiretroviral Selection Pressure

Author: Leoz, Marie, Vezain, Myriam, Alessandri-Gradt, Elodie, Coutant, Sophie, Unal, Guillemette, Tournier, Isabelle, Simon, Francois, Plantier, Jean-Christophe, 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), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, 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), and Mzembaba, Sandy
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

44. Emergence of a New Circulating B/CRF02/G Recombinant Form Spreading in France

Author: Leoz, Marie, Charpentier, Charlotte, Delaugerre, Constance, Wirden, Marc, Lemée, Veronique, Plantier, Jean-Christophe, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), COREVIH Normandie, 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), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

45. Response to Hønge et al.: Comment on Gautheret-Dejean et al.: Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections

Author: Gautheret-Dejean, Agnès, Bocobza, Jonathan, Brunet, Sylvie, Damond, Florence, Plantier, Jean-Christophe, Barin, Francis, 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), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), 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, 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), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience
Published: 2016

46. ANRS 12168 - Dynam-O study, comparing the immuno-virological and clinical responses to HAART between HIV-1 group O and group M-infected patients : results at 96 weeks

Author: Kouanfack, C., Vray, M, Kfutwah, A, Aghokeng, A, Mougnutou, R, Unal, G., Le Fouler, L, Schaeffer, L., Noumsi, N, Alessandri-Gradt, E, Delaporte, E., Simon, F., Plantier, J.-C, Hôpital Central de Yaoundé [Yaoundé], Institut de Recherche pour le Développement (IRD en Occitanie) (IRD (Occitanie)), Institut Pasteur [Paris], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Institut de Recherches Médicales et d'Etudes des Plantes Médicinales (IMPM), 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, 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), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7), Centre IRD de Montpellier (IRD), Institut de Recherches Médicales et d’Études des Plantes Médicinales [Yaoundé, Cameroon] (IMPM), Site ANRS du Cameroun Hôpital Central Yaoundé, Université de Caen Normandie (UNICAEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris] (IP), Hôpital Charles Nicolle [Rouen], CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

47. Infections à virus respiratoire syncytial (VRS) au CHU pédiatrique Charles de Gaulle de Ouagadougou, Burkina Faso

Author: F. Yonli, Marie Gueudin, Jean-Christophe Plantier, R. Ouédraogo, B. Traoré, P. Bonané, D. Kima, A. Nenebi, L. Congo, Christophe Marguet, Astrid Vabret, S. O. Ouédraogo Yugbaré, Diarra Yé, CHU Pédiatrique Charles De Gaulle [Ouagadougou, Burkina Faso] (CHUP-CDG), 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 [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Service de pneumologie, allergologie, mucoviscidose pédiatrique [Rouen], and CHU Rouen
Subjects: medicine.medical_specialty, medicine.drug_class, 030231 tropical medicine, Antibiotics, medicine.disease_cause, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, 030212 general & internal medicine, Respiratory system, Direct fluorescent antibody, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Respiratory distress, business.industry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Respiratory syncytial virus (RSV), Tropical medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business
Abstract: Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.
Published: 2016

48. Analyse génétique comparée de 19 formes recombinantes VIH-1 inter-groupes M et O et impact évolutif

Author: Moisan, A, De Oliveira, F, Cappy, P, Ngoupo, P, Vessiere, A, Lemée, V, Mourez, T., Alessandri-Gradt, E, Plantier, J, Mzembaba, Sandy, 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, 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), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), and University of Oxford [Oxford]-University of Oxford [Oxford]
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2016

49. Performance Evaluation of the New HIV-1 Quantification Assay, Xpert HIV-1 Viral Load, on a Wide Panel of HIV-1 Variants

Author: Véronique Lemée, Adeline Baron, Elodie Alessandri-Gradt, Thomas Mourez, Marie Gueudin, Jean-Christophe Plantier, Manuel Etienne, Laboratoire de virologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Service des maladies infectieuses et tropicales [Rouen]
Subjects: 0301 basic medicine, Serial dilution, 030106 microbiology, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Sensitivity and Specificity, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Viral genetics, medicine, Humans, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, GeneXpert MTB/RIF, Clinical performance, Genetic Variation, Reproducibility of Results, Viral Load, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, RNA, Viral, Reagent Kits, Diagnostic, Viral load
Abstract: Objective To evaluate the quantification performance of the new Cepheid GeneXpert HIV-1 viral load assay, on a wide panel of HIV-1 variants. Methods Clinical performance was evaluated relative to the Abbott RealTime HIV-1 assay on 285 HIV-1 seropositive samples selected to cover the assays quantification range (40 copies/mL-10,000,000 copies/mL), and included RNA undetectable or detected seropositive samples. The panel comprised 120 subtype B, 150 non-B, and 15 nontypable clinical samples; serial dilutions of 18 viral supernatants representative of the divergent viruses of HIV-1 groups N, O, and P were also tested. Results Based on samples selected according to the Abbott assay viral loads (VL), the Cepheid assay detected or quantified 222/285 (78%) samples and the Abbott assay 240/285 (84%). Xpert yielded VLs for 162 (76%) of the 213 quantifiable samples with Abbott. This difference corresponded to 51 samples with VL >40 copies/mL by the Abbott assay (all below 200 copies/mL) but detected (n = 40) or undetectable (n = 11) by the Cepheid assay. VL of samples quantifiable by both assays (n = 162) showed very strong correlation, with a Spearman correlation coefficient of 0.985 and a Bland-Altman's mean of differences of -0.01. Performance for quantification of the non-M samples showed very good correlation, with significantly higher values with Cepheid for the group N and 2 group O samples. Conclusions Our study showed that the Xpert HIV-1 VL assay offered very good performance for detection and quantification of the current HIV-1 genetic diversity; differences reported at the threshold could be an issue and requires further evaluations. The practicability of this new assay makes it suitable for low-income countries, where it could facilitate and improve follow-up of patients, as well as for high-income regions.
Published: 2016

50. First report of transmission of a highly resistant strain of HIV-1 group O

Author: Hélène Le Guillou-Guillemette, Agnès Depatureaux, Thomas Mourez, Guillemette Unal, Elodie Alessandri-Gradt, Laurence Meyer, Jean-Christophe Plantier, Jean-Marie Chennebault, Marie Leoz, Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CRSN/Faculté de médecine Université de Montréal, Centre de recherche en épidémiologie et santé des populations (CESP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: 0301 basic medicine, Immunology, Human immunodeficiency virus (HIV), Biology, medicine.disease_cause, 030112 virology, Virology, 3. Good health, law.invention, 03 medical and health sciences, Infectious Diseases, Transmission (mechanics), law, Group (periodic table), Resistant strain, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine, Immunology and Allergy
Abstract: Groupe de travail dans la liste des auteurs : RES-O Surveillance Network; International audience
Published: 2016

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