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1. Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Author: Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, André Cabié, Christophe Choquet, François Coustillères, Jean-Philippe Martellosio, Géraldine Gaube, Albert Trinh-Duc, Anne-Marie Ronchetti, Valerie Pourcher, Marie Chauveau, Karine Lacombe, Nathan Peiffer-Smadja, Pierre Housset, Aurore Perrot, Gilles Pialoux, Aurélie Martin, Vincent Dubee, Mathilde Devaux, Jérôme Frey, Charles Cazanave, Roland Liblau, Fabrice Carrat, Youri Yordanov, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Sud Francilien, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Hôtel-Dieu de Nantes, 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), CHR de Metz-Thionville, CHU Bordeaux [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'Allergologie et d'Immunologie [CHU Toulouse], Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [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), Service d'Urgences Adultes [CHU Saint-Antoine], and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Humans, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing
Abstract: International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.
Published: 2022
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2. Evidence of Sexual Transmission of Extended-Spectrum β-Lactamase–Producing Enterobacterales: A Cross-sectional and Prospective Study

Author: Laure Surgers, Thibault Chiarabini, Guilhem Royer, Hayette Rougier, Mélanie Mercier-Darty, Dominique Decré, Nadia Valin, Paul-Louis Woerther, Jean-Winoc Decousser, Pierre-Marie Girard, Karine Lacombe, Anders Boyd, Infectious diseases, APH - Methodology, APH - Global Health, 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Henri Mondor, Analyse Bio-Informatique pour la Génomique et le Métabolisme (LABGeM), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-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)-Université Paris-Saclay-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)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), CHU Henri Mondor, 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), Service de microbiologie [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), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Henri Mondor [Créteil]
Subjects: Male, Microbiology (medical), antibiotic resistance, MESH: Escherichia coli, [SDV]Life Sciences [q-bio], MESH: beta-Lactamases, virus diseases, HIV Infections, MESH: HIV Infections, beta-Lactamases, sexual transmission, MESH: Sexual and Gender Minorities, Sexual and Gender Minorities, Cross-Sectional Studies, Enterobacterales, Infectious Diseases, Escherichia coli, Prevalence, Humans, Female, epidemiology, Prospective Studies, Homosexuality, Male, carriage
Abstract: Background Extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) represent a major threat to public health. Little is known on their potential for sexual transmission. Methods We recruited individuals at a sexually transmitted infection and human immunodeficiency virus (HIV) outpatient clinic in Paris, France, in whom we evaluated the prevalence of ESBL-E intestinal carriage and, among those testing positive, the proportion with clearance 6 months thereafter. We compared carriage prevalence between groups using logistic regression adjusted for age, geographic origin, travel outside Europe, and antibiotic use in the past 6 months. Results A total of 2157 individuals participated, of whom 226 (10.5%) were ESBL-E carriers. The proportions of ESBL-E carriers varied across sexual groups and were as follows: HIV-negative men who have sex with men (MSM) and who were on preexposure prophylaxis (PrEP), 16.3% (41 of 251); HIV-negative MSM not on PrEP, 9.7% (47 of 487); HIV-positive MSM, 12.2% (61 of 500); HIV-negative men who have sex exclusively with women, 10.0% (44 of 439); and HIV-negative women who have sex with men, 6.9% (n = 33 of 480). After adjustment, ESBL-E prevalence was significantly higher in HIV-negative MSM on PrEP (P Conclusion ESBL-E carriage is more frequent in MSM undergoing PrEP or living with HIV and with increasing number of sexual partners. More research is warranted to understand the consequences of ESBL-E carriage in these populations and how transmission can be reduced.
Published: 2022
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3. Prevalence of Post-Acute COVID-19 Symptoms Twelve Months after Hospitalisation in Participants Retained in Follow-up: Analyses Stratified by Gender from a Large Prospective Cohort

Author: Ghosn, Jade, Bachelet, Delphine, Livrozet, Marine, Cervantes-Gonzalez, Minerva, Poissy, Julien, Goehringer, François, Gandonniere, Charlotte Salmon, Maillet, Mylène, Bani-Sadr, Firouzé, Martin-Blondel, Guillaume, Tattevin, Pierre, Launay, Odile, Surgers, Laure, Dudoignon, Emmanuel, Liegeon, Geoffroy, Zucman, David, Joseph, Cédric, Senneville, Eric, Yelnik, Cécile, Roger, Pierre-Marie, Faure, Karine, Gousseff, Marie, Cabié, André, Duval, Xavier, Chirouze, Catherine, Laouénan, Cedric, 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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 [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), CHU Pontchaillou [Rennes], 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 ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), 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)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Foch [Suresnes], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Gustave Dron [Tourcoing], European Atherosclerosis Society [Göteborg, Sweden] (EAS), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU de la Martinique [Fort de France], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), The French COVID cohort is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium, by a grant of the French Ministry of Health (PHRC n°20-0424), and by the ORCHESTRA project which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement N°101016167. The funders had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication., DESSAIVRE, Louise, 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], 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: Emerging infectious diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Moderate to severe COVID-19, SARS-CoV-2, Cohort, Post-acute COVID-19 symptoms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives - Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. Methods - Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results - We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale
Published: 2023
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4. Gut Microbiota Diversity of Preterm Neonates Is Associated With Clostridioides Difficile Colonization

Author: Jeanne Couturier, Patricia Lepage, Sarah Jolivet, Johanne Delannoy, Victoria Mesa, Pierre-Yves Ancel, Jean-Christophe Rozé, Marie-José Butel, Frédéric Barbut, Julio Aires, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [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 Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-12-BSV3-0025,EPIFLORE,Ecosystème intestinal du grand et très grand prématuré: analyse du microbiote, implications cliniques à court et long term(2012), ANR-13-PRTS-0018,ClosNEC,Clostridium et physiopathologie de l'entérocolite ulcéronécrosante du prématuré: approches clinique et moléculaire(2013), BILLARD, Hélène, BLANC - Ecosystème intestinal du grand et très grand prématuré: analyse du microbiote, implications cliniques à court et long term - - EPIFLORE2012 - ANR-12-BSV3-0025 - BLANC - VALID, and Programme de Recherche Translationnelle en Santé - Clostridium et physiopathologie de l'entérocolite ulcéronécrosante du prématuré: approches clinique et moléculaire - - ClosNEC2013 - ANR-13-PRTS-0018 - PRTS - VALID
Subjects: [SDV] Life Sciences [q-bio], Microbiology (medical), necrotizing enterocolitis, Infectious Diseases, gut microbiota, Clostridioides (Clostridium) difficile, microbial diversity, [SDV]Life Sciences [q-bio], Immunology, preterm neonates, colonization, Microbiology, 16S rRNA gene sequencing
Abstract: In adults, Clostridioides difficile infections are associated with alterations of the intestinal bacterial populations. Although preterm neonates (PN) are frequently colonized by C. difficile, limited data are available regarding the relationship between C. difficile and the intestinal microbiota of this specific population. Therefore, we studied the intestinal microbiota of PN from two multicenter cohorts using high-throughput sequencing of the bacterial 16S rRNA gene. Our results showed that alpha diversity was significantly higher in children colonized by C. difficile than those without colonization. Beta diversity significantly differed between the groups. In multivariate analysis, C. difficile colonization was significantly associated with the absence of postnatal antibiotherapy and higher gestational age. Taxa belonging to the Lachnospiraceae, Enterobacteriaceae, Oscillospiraceae families and Veillonella sp. were positively associated with C. difficile colonization, whereas Bacteroidales and Bifidobacterium breve were negatively associated with C. difficile colonization. After adjustment for covariables, Clostridioides, Rothia, Bifidobacterium, Veillonella, Eisenbergiella genera and Enterobacterales were more abundant in the gut microbiota of colonized children. There was no significant association between C. difficile colonization and necrotizing enterocolitis in PN. Our results suggest that C. difficile colonization in PN is related to the establishment of physiological microbiota.
Published: 2022
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5. Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

Author: Jonathan Bellet, E. Abe, Juliette Saillard, Karine Amat, Roland Landman, Jean-Claude Alvarez, Christine Katlama, Pierre de Truchis, Guillaume Gras, Dominique Costagliola, Lambert Assoumou, Pierre-Marie Girard, Séverine Gibowski, Gestionnaire, Hal Sorbonne Université, Hôpital Raymond Poincaré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
Subjects: Adult, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Etravirine, HIV Infections, 030226 pharmacology & pharmacy, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Darunavir, Pharmacology, medicine.diagnostic_test, business.industry, Rilpivirine, Lopinavir, Viral Load, Atazanavir, [SDV] Life Sciences [q-bio], chemistry, Therapeutic drug monitoring, HIV-1, Reverse Transcriptase Inhibitors, business, Viral load, medicine.drug
Abstract: INTRODUCTION Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment. OBJECTIVE To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment. METHODS During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF). RESULTS A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (-30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable. CONCLUSION Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.
Published: 2020
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6. Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV–hepatitis B coinfection

Author: Julie Chas, Patrick Miailhes, Sarah Maylin, Hayette Rougier, Caroline Lascoux-Combe, Pierre-Marie Girard, Audrey Gabassi, Anders Boyd, Fabien Zoulim, Lorenza N C Dezanet, Karine Lacombe, Constance Delaugerre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service des maladies infectieuses et tropicales [CHU 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Maladies infectieuses et tropicales [CHU Tenon], and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Male, 0301 basic medicine, Hepatitis B virus, medicine.medical_specialty, Biopsy, [SDV]Life Sciences [q-bio], Immunology, HIV Infections, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Antigen, Interquartile range, Internal medicine, medicine, Humans, Immunology and Allergy, Hepatitis B e Antigens, 030212 general & internal medicine, Coinfection, business.industry, virus diseases, cccDNA, Middle Aged, Viral Load, Hepatitis B, medicine.disease, Hepatitis B Core Antigens, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, 030104 developmental biology, Infectious Diseases, Liver, HBeAg, DNA, Viral, Female, DNA, Circular, business, Viral load, Biomarkers
Abstract: International audience; Objective: To assess whether quantified hepatitis B core-related antigen (qHBcrAg) is a surrogate marker of intrahepatic replication in HIV and hepatitis B virus (HBV) coinfection.Design: Cross-sectional study of 31 HIV-HBV-infected patients (total liver biopsies, n = 38) from a well defined cohort.Methods: Spearman's rank correlation coefficients were calculated between qHBcrAg and intrahepatic markers of HBV replication [total intrahepatic-DNA, covalently closed circular (ccc) DNA, cccDNA : total intrahepatic-DNA ratio].Results: At biopsy, 22 (71.0%) patients were hepatitis B 'e' antigen (HBeAg)-positive, 22 (71.0%) had detectable plasma HBV-DNA, and 17 (54.8%) were treated with tenofovir. Median levels (interquartile range) of intrahepatic markers were as follows: HBV cccDNA (n = 34), 0.26 copies/cell (0.4-2.89); total intrahepatic-DNA (n = 38), 2.38 copies/cell (0.58-207.9), and cccDNA : total intrahepatic-DNA ratio (n = 34), 0.05 (interquartile range = 0.01-0.12). There was a significantly strong correlation between qHBcrAg and cccDNA in all patients (Rho = 0.65, P < 0.001), while a moderate correlation was observed between qHBcrAg and total intrahepatic-DNA (Rho = 0.57, P < 0.001) or cccDNA : total intrahepatic-DNA ratio (Rho = -0.45, P = 0.01). Similar findings were observed for HBeAg-positive patients and those with detectable HBV-DNA, with the exception of qHBcrAg and cccDNA or cccDNA : total intrahepatic-DNA ratio. In contrast, no significant correlation between qHBcrAg and any intrahepatic marker was observed in HBeAg-negative patients or those with undetectable HBV-DNA. No significant difference was observed in median qHBcrAg levels across liver fibrosis stages (P = 0.5).Conclusion: qHBcrAg is a potential surrogate marker of cccDNA in HIV-HBV coinfected patients, yet might be less useful with undetectable serum HBV-DNA or HBeAg-negative status. Whether qHBcrAg provides further clinical utility compared with other serological markers remains debatable.
Published: 2020
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7. Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection

Author: Karine Lacombe, Anders Boyd, Julie Chas, Caroline Lascoux-Combe, Sarah Maylin, Pierre-Marie Girard, Patrick Miailhes, Audrey Gabassi, Lorenza N C Dezanet, Hayette Rougier, Constance Delaugerre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [CHU 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], 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: Adult, Male, medicine.medical_specialty, viruses, hepatitis B core-related antigen, HIV Infections, medicine.disease_cause, Antiviral Agents, Gastroenterology, Serology, 03 medical and health sciences, Hepatitis B, Chronic, anti-hepatitis B core antibody, 0302 clinical medicine, Antigen, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Immunology and Allergy, Hepatitis B e Antigens, Prospective Studies, 030212 general & internal medicine, Hepatitis B Antibodies, Tenofovir, Hepatitis B virus, seroclearance, biology, Coinfection, business.industry, Hazard ratio, HIV, virus diseases, Middle Aged, Hepatitis B, medicine.disease, Hepatitis B Core Antigens, digestive system diseases, 3. Good health, Infectious Diseases, HBeAg, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, biology.protein, Female, 030211 gastroenterology & hepatology, hepatitis B, Antibody, business
Abstract: Background The aim of the current study was to describe the kinetics of quantified hepatitis B core–related antigen (qHBcrAg) and quantified anti–hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus. Methods Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6–12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves. Results During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (−0.051 and −0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33–.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08–2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg Conclusions In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.
Published: 2020
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8. Tocilizumab and COVID-19: Timing of Administration Assessment

Author: Jérôme Pacanowski, V Bonnemains, Marc Garnier, B Bienvenu, V Jachiet, R Dhote, O Hinchschberger, Léo Plaçais, C Comarmond, Karine Lacombe, Arsène Mekinian, Q. Richier, Noémie Abisror, Marc Michel, HAL-SU, Gestionnaire, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Henri Mondor, Hôpital Saint-Joseph [Marseille], and Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC)
Subjects: oxygen level, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Antibodies, Monoclonal, Humanized, Article, law.invention, tocilizumab, chemistry.chemical_compound, Tocilizumab, Randomized controlled trial, law, Internal medicine, Oxygen breathing, medicine, Humans, Symptom onset, Retrospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, Mortality rate, timing of administration, COVID-19, COVID-19 Drug Treatment, Infectious Diseases, chemistry, Cohort, Oxygen level, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Recent evidence showed greater efficacy of tocilizumab (TCZ) in the subgroups of COVID-19 patients who presented with symptoms for less than 7 days and in those only receiving oxygen. We retrospectively analyzed a compassionate use cohort to determine the best timing for TCZ injection. We showed no association between the timing of injection after symptom onset and the efficacy of TCZ on mortality. We then investigated whether the oxygen level at the time of TCZ injection impacted the mortality rate. Our study finally suggested that TCZ could be less effective when oxygen requirement is >11 L/min and we hypothesized that earlier administration could be associated with better outcome. However, randomized clinical trials are required to confirm this hypothesis.
Published: 2022
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9. The burden of NAFLD in type 2 diabetic subjects from the general population: A Nationwide population-based follow-up study (NASHCO)

Author: Oumarou Nabi, Jerome Boursier, Nathanaël Lapidus, Philippe Mathurin, Victor de Ledinghen, Jean‐Michel Petit, Marcel Goldberg, Marie Zins, Karine Lacombe, Lawrence Serfaty, 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 santé publique [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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Lille, CHU Bordeaux [Bordeaux], Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), 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), Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and HAL UVSQ, Équipe
Subjects: Liver Cirrhosis, obesity, Hepatology, Forns index, [SDV]Life Sciences [q-bio], fatty liver index, [SDV] Life Sciences [q-bio], advanced fibrosis, Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Risk Factors, cardiovascular disease, extrahepatic malignancy mortality, Humans, Longitudinal Studies, Prospective Studies, type 2 diabetes, chronic kidney disease, Follow-Up Studies
Abstract: International audience; Background: The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. Method: This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5 years. Results: Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P
Published: 2022
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10. Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis

Author: Thomas Hueso, Anne-Sophie Godron, Emilie Lanoy, Jérôme Pacanowski, Laura I. Levi, Emmanuelle Gras, Laure Surgers, Amina Guemriche, Jean-Luc Meynard, France Pirenne, Salim Idri, Pierre Tiberghien, Pascal Morel, Caroline Besson, Rémy Duléry, Sylvain Lamure, Olivier Hermine, Amandine Gagneux-Brunon, Nathalie Freymond, Sophie Grabar, Karine Lacombe, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Saclay, 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Versailles André Mignot (CHV), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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, Service d'hématologie clinique et de thérapie cellulaire [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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de santé publique [CHU Saint-Antoine], European Commission, EC: 101021793, Sorbonne Université, This study was supported by the program Emergency Support Instrument (ESI) of the European Commission (project CCPEFS, grant number 101021793) and Sorbonne University., and HAL UVSQ, Équipe
Subjects: Cancer Research, SARS-CoV-2, Immunization, Passive, COVID-19, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Translational research, Antibodies, Viral, Article, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Humans, Immunotherapy, Propensity Score, COVID-19 Serotherapy
Abstract: International audience; Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated (n = 81) or not (n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56–74.9) and 77.5% (95% CI = 68.5–87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20–exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31–80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.
Published: 2022
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11. Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

Author: Tomas Urbina, Jean-Rémi Lavillegrand, Marc Garnier, Arsene Mekinian, Jerome Pacanowski, Nathalie Mario, Guillaume Dumas, Geoffroy Hariri, Antoine Pilon, Lucie Darrivère, Muriel Fartoukh, Bertrand Guidet, Eric Maury, Judith Leblanc, Yannick Chantran, Olivier Fain, Karine Lacombe, Guillaume Voiriot, Hafid Ait-Oufella, Service de Réanimation Médicale [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), Département Médico-Universitaire réanimation anesthésie médecine péri-opératoire [Sorbonne Université] (DMU DREAM), CHU Tenon [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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne [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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Service de biochimie [CHU Saint-Antoine], Service des Soins Intensifs [CHU Saint-Antoine], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Groupe de recherche clinique en anesthésie réanimation médecine périopératoire [CHU Pitié-Salpétrière] (GRC ARPE), CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Critical Illness, Immunology, Antibodies, Monoclonal, Humanized, intensive care unit, Antiviral Agents, Microbiology, Cohort Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, cytokine, Humans, Molecular Biology, Aged, Retrospective Studies, Inflammation, SARS-CoV-2, Interleukin-6, COVID-19, Fibrinogen, Cell Biology, Tocilizumab, Middle Aged, RC581-607, Respiration, Artificial, COVID-19 Drug Treatment, C-Reactive Protein, Treatment Outcome, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Immunologic diseases. Allergy, Biomarkers
Abstract: International audience; Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.
Published: 2022
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12. Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis

Author: Peretti, N., Vimont, Alexandre, Mas, E., Ferrières, J., Tounian, P., Lemale, J., Boccara, F., Di Filippo, M., Charriere, S., Moulin, P., Poinsot, P., Cottin, Y., Ducluzeau, P. H., Dourmap, C., Cariou, B., Farnier, M., Paillard, F., Pradignac, A., Yelnik, C., Gallo, A., Bruckert, E., Beliard, S., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Groupe de recherche clionique Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l’immunodéficience humaine (VIH) (GRC 22 - C²MV), Hôpital Louis Pradel [CHU - HCL], Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], Hôpital de Hautepierre [Strasbourg], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), the New French Atherosclerosis Society and the French national project CHOPIN (CHOlesterol Personalized Innovation), French Registry of Familial Hypercholesterolemia (REFERCHOL) investigators, ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), CarMeN, laboratoire, CHOPIN - - CHOPIN2016 - ANR-16-RHUS-0007 - RHUS - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l’immunodéficience humaine (GRC22 C²MV), Service de Cardiologie [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 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)-Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [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 Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)-Service de cardiologie [CHU Tenon]
Subjects: cardiovascular risk, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, children, familial hypercholesterolemia, risk factor, treatment, Pediatrics, Perinatology and Child Health, statin, atherosclerotic cardiovascular disease, genetic, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Ldl
Abstract: International audience; OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score \textgreater100, and/or stenosis of \textgreater50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P \textless .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.
Published: 2023
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13. [Letter] Cutaneous diphtheria: 3 case-reports to discuss determinants of re-emergence in resource-rich settings

Author: Levi, Laura, Barbut, Frédéric, Chopin, Dorothée, Rondeau, Paul, Lalande, Valérie, Jolivet, Sarah, Badell, Edgar, Brisse, Sylvain, Lacombe, Karine, Surgers, Laure, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Bactériologie [CHU Saint-Antoine], Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Corynebacterium diphtheriae, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, vaccine skepticism, emergence, Diphtheria, complex mixtures, Corynebacterium ulcerans
Abstract: International audience; Diphtheria is a re-emerging disease in resource-rich settings. We here report three cases of cutaneous diphtheria diagnosed and managed in our infectious disease department and discuss the determinants of its re-emergence. Migration, travel and vaccine skepticism are key factors not only for diphtheria re-emergence, but for the future of most preventable diseases.
Published: 2021
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14. Persistent COVID-19 in an immunocompromised host treated by SARS-CoV-2-specific monoclonal antibodies

Author: Bailly, Benoit, Péré, Helene, Veyer, David, Berceanu, Ana, Daguindau, Etienne, Roux, Pauline, Hermine, Olivier, de Lamballerie, Xavier, Bastard, Paul, Lacombe, Karine, Autran, Brigitte, Angelot Delettre, Fanny, Casanova, Jean Laurent, Imbeaud, Sandrine, Clairet, Anne Laure, Kroemer, Marie, Spehner, Laurie, Robillard, Nicolas, Puech, Julien, Marty-Quinternet, Solène, Lepiller, Quentin, Chirouze, Catherine, Bouiller, Kevin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'hématologie, Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and Laboratoire Chrono-environnement (UMR 6249) (LCE)
Subjects: [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021
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15. Persistent HBV replication and serological response during up to 15 years of tenofovir-based antiretroviral therapy in HIV/HBV-coinfected patients: a multicentre prospective cohort study

Author: Audrey Gabassi, Caroline Lascoux-Combe, Karine Lacombe, Sarah Maylin, Lorenza N C Dezanet, Patrick Miailhes, Julie Chas, Constance Delaugerre, Anders Boyd, Hayette Rougier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU 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), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), 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), Infectious diseases, APH - Methodology, and APH - Global Health
Subjects: Microbiology (medical), medicine.medical_specialty, HBsAg, Hepatitis B virus, Viremia, HIV Infections, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Hepatitis B e Antigens, Prospective Studies, Prospective cohort study, Tenofovir, Pharmacology, Hepatitis, Hepatitis B Surface Antigens, business.industry, Coinfection, virus diseases, medicine.disease, digestive system diseases, 3. Good health, Infectious Diseases, HBeAg, DNA, Viral, 030211 gastroenterology & hepatology, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives To determine the extent of hepatitis B virus (HBV) suppression and its association with seroclearance of hepatitis ‘e’ antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HIV/HBV-coinfected patients undergoing long-term tenofovir-based antiretroviral therapy (ART). Methods We prospectively followed 165 HIV/HBV-coinfected patients undergoing tenofovir-based ART. Serum HBV-DNA viral loads and HBeAg and HBsAg status were obtained at tenofovir initiation and every 6–12 months. We calculated the proportion achieving virological response (VR, Results During a median 8.1 years (IQR = 4.0–13.2) of tenofovir treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up = 608 IU/mL, range = 67–52 400 000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during tenofovir treatment: 15.1% (n = 14/93) at 5 years, 3.2% (n = 2/62) at 10 years and, 3.2% (n = 1/31) at 15 years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, P = 0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, P = 0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (P Conclusions During long-term tenofovir-based ART for HIV/HBV coinfection, persistent HBV viraemia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.
Published: 2021
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16. Profiles of liver fibrosis evolution during long-term tenofovir treatment in HIV-positive patients coinfected with hepatitis B Running title: Liver fibrosis evolution in HIV/HBV coinfection

Author: Dezanet, Lorenza, Miailhes, Patrick, Lascoux-Combe, Caroline, Chas, Julie, Maylin, Sarah, Gabassi, Audrey, Rougier, Hayette, Delaugerre, Constance, Lacombe, Karine, Boyd, Anders, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de maladies infectieuses et tropicales [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 de Paris (UP), Service des maladies infectieuses et tropicales [CHU 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), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), 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), Gestionnaire, HAL Sorbonne Université 5, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Service de Maladies infectieuses et tropicales [CHU Tenon]
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Background & AimsData on liver fibrosis evolution and its involvement in liver-related morbidity are scarce in individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection during treatment. We identified profiles of liver fibrosis evolution in coinfected patients undergoing tenofovir (TDF).MethodsWe included 169 HIV-HBV-coinfected patients on TDF-based antiretroviral therapy. Virological and clinical data were obtained at TDF-initiation and every 6-12 months. From data on non-invasive liver fibrosis assessments collected yearly (FibroTest®), we established clusters of individuals with similar liver fibrosis evolution using group-based trajectory models.ResultsFour profiles of liver fibrosis evolution were established from a median follow-up of 7.6 years (IQR = 3.1-13.1): low fibrosis with no progression (29.6%, profile A), low fibrosis with progression (22.5%, profile B), moderate fibrosis with high fluctuation (39.6%, profile C), and cirrhosis with no regression (8.3%, profile D). When compared to profile A, baseline HBeAg-positive status was associated with profiles B (P = .007) and C (P = .004), older age with profiles C (P < .001) and D (P = .001), exposure to second-generation protease inhibitors with profile C (P = .004), and CD4+
Published: 2021
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17. Anti-gp41 antibody levels reflect HIV viral suppression and cellular reservoir in long-term antiretroviral-treated trial participants

Author: Corinne Jadand, Maxime Grude, Mathilde Ghislain, Marie-Laure Nere, Vincent Calvez, Laurence Meyer, Francis Barin, Philippe Flandre, Heloise Delagreverie, Cécile Goujard, Sidonie Lambert-Niclot, François Raffi, Catherine Leport, Christine Katlama, Constance Delaugerre, Gestionnaire, Hal Sorbonne Université, 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 (UMR_S_944)), Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), 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 des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), Time Factors, Sustained Virologic Response, Anti-HIV Agents, [SDV]Life Sciences [q-bio], 030106 microbiology, HIV Infections, Antibodies, Viral, Virus, 03 medical and health sciences, 0302 clinical medicine, Antigen, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Humans, Medicine, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pharmacology, biology, medicine.diagnostic_test, business.industry, Antibody titer, virus diseases, Middle Aged, HIV Envelope Protein gp41, [SDV] Life Sciences [q-bio], Titer, Cross-Sectional Studies, Infectious Diseases, Immunoassay, Immunology, HIV-1, biology.protein, RNA, Viral, Biomarker (medicine), Female, France, Antibody, business
Abstract: Background A major challenge to HIV cure strategies is the quantification of persistent reactivation-prone virus in people living with HIV. Objectives To determine whether anti-gp41 antibody levels correlate with viral suppression and HIV-1 DNA levels in patients on ART. Methods Participants with plasma HIV-1 RNA below 50 copies/mL for >12 months were included from three ANRS cohorts (COPANA, MONOI and APROCO). Antibody levels to gp41 were measured by a low-sensitivity enzyme-linked immunoassay. Correlations with patient and virus characteristics, plasma HIV-1 RNA load (standard and ultrasensitive tests) and cell-associated HIV-1 DNA were assessed. Results Median age was 41 years and 77.5% of the 683 participants were men. Median CD4+ T cell count was 582 cells/mm3 and median viral suppression duration was 6.6 years (IQR 2.0-9.5). The overall median anti-gp41 antibody titre was 1.3 (IQR 0.6-1.9); median HIV-1 DNA level was 2.6 (IQR 2.1-3.0) log10 copies/106 leucocytes; and HIV-1 RNA was undetectable in 56% of samples. A lower titre of anti-gp41 antibodies correlated with male gender, longer viral suppression and lower HIV-1 DNA burden. Sustained undetectable HIV-1 RNA was associated with lower anti-gp41 levels [median 1.1 (IQR 0.5-1.6) versus 1.4 (IQR 0.7-1.9), P = 0.009]. Conclusions Anti-gp41 levels decreased with the duration of antiviral suppression on ART. Lower titres were associated with lower HIV-1 DNA levels and longer duration of viral suppression, reflecting minimal antigen stimulation. Anti-gp41 antibody titration may be a useful biomarker reflecting long-term HIV-1 suppression on ART.
Published: 2019
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18. Comorbidities Are Associated with Fibrosis in NAFLD Subjects: A Nationwide Study (NASH-CO Study)

Author: Karine Lacombe, Jérôme Boursier, Lawrence Serfaty, Philippe Mathurin, Victor de Ledinghen, Marie Zins, Marcel Goldberg, Oumarou Nabi, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Recherche Saint-Antoine (CR Saint-Antoine), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP]
Subjects: Adult, Liver Cirrhosis, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Population, Forns Index, Renal function, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Risk Factors, Internal medicine, Chronic kidney disease, medicine, Humans, Fatty Liver Index, Renal Insufficiency, Chronic, education, Cancer, education.field_of_study, business.industry, Fatty liver, Hepatology, medicine.disease, Cardiovascular disease, Colorectal cancer, 3. Good health, [SDV] Life Sciences [q-bio], Cardiovascular Diseases, 030220 oncology & carcinogenesis, Cohort, Population study, 030211 gastroenterology & hepatology, business, Glomerular Filtration Rate
Abstract: International audience; Background: The relationship between the severity of NAFLD and extra-hepatic events such as cardiovascular disease (CVD), extra-hepatic cancer (EHC) or chronic kidney diseases (CKD) has not been clearly investigated in the general population.Aims: The aim of this study was to assess whether the severity of fibrosis in NAFLD subjects was associated with extra-hepatic diseases based on noninvasive markers in a large population-based cohort.Methods: The study population included a cohort of 118,664 participants from the nationwide CONSTANCES cohort. After excluding individuals with excessive alcohol consumption and other causes of liver disease, 102,344 were included. The noninvasive diagnosis of NAFLD and fibrosis was performed using a combination of the Fatty Liver Index (FLI) and the Forns Index. The history of CVD or EHC was recorded by a physician, and CKD was defined by a glomerular filtration rate < 60 ml/mn.Results: The prevalence of NAFLD (FLI > 60) was 18.2%, 10% with mild fibrosis (Forns Index < 4.2), 7.7% with intermediate fibrosis (Forns Index 4.2-6.9), and 0.4% with advanced fibrosis (Forns Index > 6.9). The prevalence of CVD, EHC, or CKD increased significantly with the severity of fibrosis (p < 0.0001). When adjusted for demographic, metabolic risk factors, and smoking, NAFLD with intermediate or advanced fibrosis remained associated with CVD (OR 1.36, p < 0.0001 and OR 3.07, p < 0.0001, respectively), EHC (OR 1.24, p = 0.001 and OR 1.64, p = 0.004, respectively), and CKD (OR 1.18, p = 0.03 and OR 2.09, p < 0.0001, respectively).Conclusions: In a large adult population-based cohort, there is a dose-dependent relationship between the severity of fibrosis and CVD, EHC, or CKD in NAFLD subjects.
Published: 2021
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19. Prospective evaluation of blood Epstein-Barr virus DNA load and antibody profile in HIV-related non-Hodgkin lymphomas

Author: Sophie Prevot, Raphaele Germi, Nicolas Mounier, Yassine Taoufik, Michele Algarte-Genin, Dominique Costagliola, Patrice Morand, Rémi Lancar, Anastasiia Filippova, Houria Hendel-Chavez, Bruno Marchou, Julien Lupo, Caroline Besson, Marie-Caroline Meyohas, Marialuisa Partisani, Fabrice Bonnet, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], Hôpital l'Archet, Les Hôpitaux Universitaires de Strasbourg (HUS), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier de Versailles André Mignot (CHV), 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, Admin, Oskar, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, medicine.medical_specialty, Immunology, medicine.disease_cause, Gastroenterology, Virus, Serology, Epstein–Barr virus, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Immunology and Allergy, 030212 general & internal medicine, Epstein–Barr virus antibodies, Whole blood, biology, business.industry, HIV, Non-Hodgkin's lymphoma, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Epstein–Barr virus DNA load, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, business, Viral load
Abstract: International audience; Objectives: The value of Epstein–Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. Design: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. Methods: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. Results: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P = 0.52). Conclusions: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.
Published: 2021
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20. An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19

Author: Lionel Piroth, Bruno Mourvillier, Joy Mootien, François-Xavier Lescure, Emmanuel Faure, S. Gallien, Dominique Costagliola, Jean-Christophe Richard, Noemie Mercier, Florent Wallet, Yazdan Yazdanpanah, Marion Noret, Claire Andrejak, Jean-Philippe Lanoix, Julien Poissy, Johan Courjon, Saad Nseir, François Danion, Violaine Tolsma, Alain Makinson, Odile Launay, Raphaël Clere-Jehl, Bruno Lina, Drifa Belhadi, Valérie Pourcher, Antoine Kimmoun, Karine Lacombe, Juliette Saillard, Maude Bouscambert-Duchamp, Stéphane Jauréguiberry, Charles Burdet, Toni Alfaiate, Olivier Epaulard, Minh Patrick Lê, Gilles Peytavin, Elisabeth Botelho-Nevers, Thérèse Staub, Guillaume Martin-Blondel, Alpha Diallo, Lila Bouadma, Aline Dechanet, François Goehringer, Florence Ader, Nathan Peiffer-Smadja, Jean-Christophe Navellou, Christelle Delmas, Rostane Gaci, Kevin Bouiller, Maya Hites, André Cabié, Jean Reuter, Sylvie Leroy, Axelle Dupont, François Raffi, Amandine Gagneux-Brunon, Jean Reignier, Clément Dubost, Hospices Civils de Lyon (HCL), 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), 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, National Institute for Health Research [Cambridge, UK], Imperial College London, 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), CHU Lille, Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), 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), 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), ANRS France Recherche Nord & sud Sida-hiv hépatites, Institut de Santé Publique, Université de Médecine Carol Davila, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Réanimation Médicale [CHRU Nancy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Les Hôpitaux Universitaires de Strasbourg (HUS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Fédération Hospitalo-Universitaire (OMICARE), Centre de Recherche d’Immunologie et d’Hématologie [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Etablissement français du don du sang [Montpellier], CHU de la Martinique [Fort de France], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Université Paris-Saclay, Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université de Paris (UP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Université Lille Nord de France (COMUE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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), 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), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), CHU Toulouse [Toulouse], Physiopathologie et biothérapies des infections muqueuses (GIMAP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération d’Infectiologie Multidisciplinaire de l’Arc Alpin [CHU Grenoble-Alpes], Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-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), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Institut des Agents Infectieux [Lyon] (IAI), Réseau national de recherche clinique en infectiologie (RENARCI), CHU Amiens-Picardie, Université libre de Bruxelles (ULB), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Lorraine (UL), Hôpital Bicêtre, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Lille, Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), 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)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), 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), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière] (CNRpalu), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses 94000 Créteil, France, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er 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), Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), CHU Grenoble, Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), 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), Laboratoire Chrono-environnement (UMR 6249) (LCE), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), 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), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Lopinavir/ritonavir, law.invention, 0302 clinical medicine, Randomized controlled trial, law, immune system diseases, MESH: Antiviral Agents* / therapeutic use, 030212 general & internal medicine, MESH: Treatment Outcome, education.field_of_study, MESH: Middle Aged, virus diseases, Lopinavir, General Medicine, MESH: Lopinavir / therapeutic use, 3. Good health, Infectious Diseases, MESH: Interferon beta-1a / therapeutic use, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pharmaceutical Preparations, MESH: Hydroxychloroquine / therapeutic use, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, medicine.drug, Hydroxychloroquine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Antiviral Agents, 03 medical and health sciences, Interferon β-1a, Internal medicine, medicine, Humans, education, Adverse effect, MESH: COVID-19* / drug therapy, MESH: Drug Combinations, MESH: Humans, business.industry, SARS-CoV-2, Drug Repositioning, Interferon beta-1a, COVID-19, MESH: Adult, MESH: Male, MESH: Ritonavir / therapeutic use, Ritonavir, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support.Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely.Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.
Published: 2021
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21. Severe COVID-19 infection in a patient with paroxysmal nocturnal hemoglobinuria on eculizumab therapy

Author: Patrick Ingiliz, Karine Lacombe, Simona Lapusan, Alexis Genthon, Arsène Mekinian, Fella M. ’Hammedi-Bouzina, Eolia Brissot, Pierre Baylac, Jérôme Pacanowski, Nadia Valin, Tomas Urbina, Mohamad Mohty, T. Chiarabini, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de Réanimation Médicale [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Service de rhumatologie [CHU Saint-Antoine], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL-SU, Gestionnaire, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 2019-20 coronavirus outbreak, Pediatrics, medicine.medical_specialty, Cancer Research, Coronavirus disease 2019 (COVID-19), PNH, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hemoglobinuria, Paroxysmal, Antibodies, Monoclonal, Humanized, tocilizumab, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, pre-exposure prophylaxis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, virus diseases, Hematology, Eculizumab, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Paroxysmal nocturnal hemoglobinuria, eculizumab, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract: The course of the COVID-19 infection has been better understood since the first identification of a novel beta-coronavirus (SARS-CoV-2) in early January 2020 in Wuhan, China [1]. Some individuals w...
Published: 2021
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22. Erratum to: Kinetics of Hepatitis B Core\textendashRelated Antigen and Anti\textendashHepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus\textendashHepatitis B Coinfection

Author: Dezanet, Lorenza N C, Maylin, Sarah, Gabassi, Audrey, Rougier, Hayette, Miailhes, Patrick, Lascoux-Combe, Caroline, Chas, Julie, Girard, Pierre-Marie, Delaugerre, Constance, Lacombe, Karine, Boyd, Anders, Gestionnaire, Hal Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), 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), Institut de Médecine et d'Epidémiologie Appliquées (IMEA), Service des maladies infectieuses et tropicales [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 maladies infectieuses et tropicales [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], Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], and CHU Saint-Antoine [AP-HP]
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Published: 2021
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23. Tocilizumab in Coronavirus Disease 2019: Give It Time!

Author: Léo Plaçais, Q. Richier, Karine Lacombe, Olivier Hermine, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: Microbiology (medical), 2019-20 coronavirus outbreak, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Monoclonal, Humanized, Virology, COVID-19 Drug Treatment, chemistry.chemical_compound, AcademicSubjects/MED00290, Tocilizumab, Infectious Diseases, chemistry, Correspondence, Humans, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Published: 2021
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24. Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19

Author: Noël Zahr, Valérie Pourcher, Julien Mayaux, Joe-Elie Salem, Estelle Gandjbakhch, Yves Allenbach, Guillaume Hékimian, Saïk Urien, Alexandre Bleibtreu, Olivier Benveniste, Olivier Paccoud, Alain Combes, Christian Funck-Brentano, Benoit Llopis, David Saadoun, Patrice Cacoub, Bruno Pinna, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Pharmacologie Clinique [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 Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Cardiologie [CHU Pitié-Salpêtrière], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], HAL-SU, Gestionnaire, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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 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)-Institut E3M [CHU Pitié-Salpêtrière], and Garnier, Sophie
Subjects: Adult, Male, medicine.medical_specialty, 030226 pharmacology & pharmacy, High-performance liquid chromatography, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Intensive care, medicine, Humans, Pharmacology (medical), Retrospective Studies, Volume of distribution, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, Clinical Pharmacology, Hydroxychloroquine, Middle Aged, Confidence interval, COVID-19 Drug Treatment, 3. Good health, Bioavailability, Hospitalization, [SDV] Life Sciences [q-bio], Pharmacodynamics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, business, Covid-19, medicine.drug
Abstract: Summary Background Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. Methods We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n = 149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. Results HCQ doses ranged from 200 to 800 mg/day administered for 1 to 11 days and median HCQ plasma concentration was 151 ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9 L/h (21.2) and 6690 L (16.1). The derived elimination half-life (t1/2) was 102 h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68 L/h, 2440 L and 19.5 h, respectively. Within 72 h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240 ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs). Conclusion The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600 mg HCQ followed by 600 mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72 hours in ≥ 60% (95% confidence interval: 49.5–69.0%) of COVID-19 patients.
Published: 2021
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25. Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial

Author: Benjamin Gaborit, Bernard Vanhove, Marie-Anne Vibet, Aurélie Le Thuaut, Karine Lacombe, Vincent Dubee, Florence Ader, Virginie Ferre, Eric Vicaut, Jéremie Orain, Morgane Le Bras, Anne Omnes, Laetitia Berly, Alexandra Jobert, Pascale Morineau-Le Houssine, Karine Botturi, Régis Josien, Laurent Flet, Nicolas Degauque, Sophie Brouard, Odile Duvaux, Alexandra Poinas, François Raffi, POLYCOR study group, Gestionnaire, Hal Sorbonne Université, Centre hospitalier universitaire de Nantes (CHU Nantes), 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 Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hospices Civils de Lyon (HCL), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), and 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)
Subjects: Time Factors, Moderate pneumonia, Swine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Severity of Illness Index, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, Pharmacology (medical), 030212 general & internal medicine, Neutralizing antibody, Randomized Controlled Trials as Topic, 0303 health sciences, education.field_of_study, lcsh:R5-920, biology, Anti-SARS-CoV-2 antibodies, 3. Good health, [SDV] Life Sciences [q-bio], Spike Glycoprotein, Coronavirus, Immunotherapy, lcsh:Medicine (General), medicine.medical_specialty, Population, Placebo, Antibodies, Monoclonal, Humanized, Phase 2, 03 medical and health sciences, Therapeutic approach, Clinical Trials, Phase II as Topic, Double-Blind Method, Internal medicine, Severity of illness, medicine, Animals, Humans, education, COVID-19 Serotherapy, 030304 developmental biology, business.industry, SARS-CoV-2, Immunization, Passive, Oxygen Inhalation Therapy, COVID-19, medicine.disease, Antibodies, Neutralizing, Pneumonia, Immunoglobulin G, biology.protein, business
Abstract: Background Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. Methods Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. Discussion This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. Trial registration ClinicalTrials.gov NCT04453384, registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.
Published: 2021
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26. Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Author: Martin Martinot, Aude Jary, Samira Fafi-Kremer, Valentin Leducq, Heloise Delagreverie, Marc Garnier, Jérôme Pacanowski, Arsène Mékinian, France Pirenne, Pierre Tiberghien, Vincent Calvez, Catherine Humbrecht, Anne-Geneviève Marcelin, Karine Lacombe, Hôpitaux Civils de Colmar, 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), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Strasbourg], Groupe de recherche clinique en anesthésie réanimation médecine périopératoire [CHU Pitié-Salpétrière] (GRC ARPE), Département Médico-Universitaire réanimation anesthésie médecine péri-opératoire [Sorbonne Université] (DMU DREAM), CHU Tenon [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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Microbiology (medical), Adenosine monophosphate, Coronavirus disease 2019 (COVID-19), viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, RNA-dependent RNA polymerase, Viremia, medicine.disease_cause, Virus, 03 medical and health sciences, chemistry.chemical_compound, medicine, B cell, Immunodeficiency, Mutation, business.industry, virus diseases, medicine.disease, Virology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, chemistry, business
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.
Published: 2021
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27. Long‐term clinical benefits of Sofosbuvir‐based direct antiviral regimens for patients with chronic hepatitis C in Central and West Africa

Author: Alain Attia, Nicolas Rouveau, Maud Lemoine, Moussa Seydi, Marie Libérée Nishimwe, Raoul Moh, Charles Kouanfack, Maame Esi Woode, Maël Baudoin, Sylvie Boyer, Karine Lacombe, Babacar Sylla, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Monash University [Melbourne], St Mary's Hospital [London], Imperial College London, Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Faculté des Sciences - Université de Dschang [Cameroun], Université de Dschang, Hôpital Central de Yaoundé [Yaoundé], PACCI Programme [Abidjan, Côte d'Ivoire] (Projet MONOD), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), UFR des sciences médicales d'Abidjan [Côte d'Ivoire], University Hospital of Fann [Dakar, Senegal], Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Centre Hospitalier Universitaire de Yopougon [Abidjan, Côte d'Ivoire] (CHU de Yopougon), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Dupuis, Christine
Subjects: medicine.medical_specialty, Cirrhosis, Sofosbuvir, [SDV]Life Sciences [q-bio], Disease, Antiviral Agents, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Markov simulation, low-income countries, Internal medicine, Ribavirin, medicine, Humans, Africa South of the Sahara, Hepatology, business.industry, Public health, Liver Neoplasms, Hepatitis C, Hepatitis C, Chronic, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Cote d'Ivoire, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Africa, direct-acting antivirals (DAAs), 030211 gastroenterology & hepatology, hepatitis C, business, medicine.drug
Abstract: International audience; Background: In Sub-Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long-term clinical benefits of treating CHC with sofosbuvir-based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct-acting antiviral (DAAs) effectiveness in West and Central Africa.Methods: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life-years saved (LYS); (b) life-years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty.Results: Sofosbuvir-based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity.Conclusion: Sofosbuvir-based treatment could significantly reduce CHC-related mortality and help control CHC-related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures.
Published: 2020
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28. Report on Electroencephalographic Findings in Critically Ill Patients with COVID ‐19

Author: Valérie Pourcher, Samir Medjebar, Christine Soufflet, Hervé Vespignani, Pierre Yves Frouin, Damien Colas, Bruce S. Lavin, Louis Maillard, Olivier Paccoud, Université de Lorraine (UL), CHU Necker - Enfants Malades [AP-HP], CIC Pitié BT, 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Service des maladies infectieuses et tropicales [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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], and CHU Saint-Antoine [AP-HP]
Subjects: Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Illness, [SDV]Life Sciences [q-bio], Central nervous system, Clinical Neurology, Electroencephalography, Brief Communication, Arousal, 03 medical and health sciences, 0302 clinical medicine, Altered Mental Status, medicine, Humans, Aged, Brain Diseases, medicine.diagnostic_test, business.industry, Critically ill, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, COVID-19, Middle Aged, 3. Good health, Delta wave, 030104 developmental biology, medicine.anatomical_structure, Neurology, Cohort, Neurology (clinical), Brief Communications, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; In March 2020, we treated a cohort of 26 critically ill hospitalized SARS-CoV-2-infected patients who underwent electroencephalography to assess unexplained altered mental status, loss of consciousness, or poor arousal and responsiveness. Of the 26 patients studied, 5 patients had electroencephalograms that showed periodic discharges consisting of high-amplitude frontal monomorphic delta waves with absence of epileptic activity. These findings may suggest central nervous system injury potentially related to COVID-19 in these patients. ANN NEUROL 2020.
Published: 2020
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29. Prévalence et Facteurs de risque de la Stéatose Hépatique Non Alcoolique et la Fibrose avancée en Population générale: Etude nationale française NASH-CO

Author: Philippe Mathurin, Jérôme Boursier, Lawrence Serfaty, Marie Zins, Oumarou Nabi, Karine Lacombe, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en épidémiologie et santé des populations (CESP), 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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Lille, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Liver Cirrhosis, Male, [SDV]Life Sciences [q-bio], Forns Index, Type 2 diabetes, MESH: Risk Assessment, Gastroenterology, 0302 clinical medicine, MESH: Risk Factors, Non-alcoholic Fatty Liver Disease, Risk Factors, Nonalcoholic fatty liver disease, Prevalence, Alanine aminotransferase, ComputingMilieux_MISCELLANEOUS, MESH: Aged, education.field_of_study, MESH: Middle Aged, Middle Aged, Advanced fibrosis, Type 2 Diabetes, 3. Good health, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, MESH: Liver Cirrhosis, Adult, medicine.medical_specialty, Population, Risk Assessment, 03 medical and health sciences, MESH: Cross-Sectional Studies, Internal medicine, medicine, Fatty Liver Index, Humans, Obesity, education, MESH: Prevalence, Aged, MESH: Humans, Hepatology, MESH: Non-alcoholic Fatty Liver Disease, business.industry, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, medicine.disease, MESH: Male, Confidence interval, MESH: France, Cross-Sectional Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; The burden of nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis has not been reported so far at a nationwide level in Europe. According to a meta-analysis, the prevalence of NAFLD in European countries ranged from 4% to 50%, reflecting the heterogeneity of study populations. 1 The French CONSTANCES population-based cohort was designed as a large representative sample for age, gender, and socioeconomic status of the French adult population. 2 The present study was aimed to assess the prevalence of NAFLD and advanced fibrosis in the CONSTANCES cohort by using noninvasive markers, and to examine risk factors associated with these conditions.
Published: 2020
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30. Association of Hepatitis B Core-Related Antigen and Antihepatitis B Core Antibody With Liver Fibrosis Evolution in Human Immunodeficiency Virus-Hepatitis B Virus Coinfected Patients During Treatment With Tenofovir

Author: Romuald Cruchet, Julie Chas, Audrey Gabassi, Constance Delaugerre, Patrick Miailhes, Karine Lacombe, Lorenza N C Dezanet, Hayette Rougier, Pierre-Marie Girard, Anders Boyd, Sarah Maylin, Caroline Lascoux-Combe, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-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), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [CHU 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), 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), Gestionnaire, HAL Sorbonne Université 5, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Service de Maladies infectieuses et tropicales [CHU Tenon]
Subjects: medicine.medical_specialty, Cirrhosis, hepatitis B core-related antigen, antihepatitis B core antibody, medicine.disease_cause, Gastroenterology, Virus, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Major Article, 030212 general & internal medicine, liver fibrosis, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hepatitis B virus, biology, human immunodeficiency virus, business.industry, cirrhosis, Hazard ratio, Hepatitis B, medicine.disease, 3. Good health, Infectious Diseases, AcademicSubjects/MED00290, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Antibody, business, Hepatic fibrosis
Abstract: Background Quantitative hepatitis B core-related antigen (qHBcrAg) or antihepatitis B core antibody (qAnti-HBc) could be useful in monitoring liver fibrosis evolution during chronic hepatitis B virus (HBV) infection, yet it has not been assessed in human immunodeficiency virus (HIV)-HBV-coinfected patients undergoing treatment with tenofovir (TDF). Methods One hundred fifty-four HIV-HBV-infected patients initiating a TDF-containing antiretroviral regimen were prospectively followed. The qHBcrAg and qAnti-HBc and liver fibrosis assessment were collected every 6–12 months during TDF. Hazard ratios (HRs) assessing the association between qHBcrAg/qAnti-HBc and transitions from none/mild/significant fibrosis to advanced fibrosis/cirrhosis (progression) and from advanced fibrosis/cirrhosis to none/mild/significant fibrosis (regression) were estimated using a time-homogeneous Markov model. Results At baseline, advanced liver fibrosis/cirrhosis was observed in 40 (26%) patients. During a median follow-up of 48 months (interquartile range, 31–90), 38 transitions of progression (IR = 7/100 person-years) and 34 transitions of regression (IR = 6/100 person-years) were observed. Baseline levels of qHBcrAg and qAnti-HBc were not associated with liver fibrosis progression (adjusted-HR per log10 U/mL = 1.07, 95% confidence interval [CI] = 0.93–1.24; adjusted-HR per log10 Paul-Ehrlich-Institute [PEI] U/mL = 0.85, 95% CI = 0.70–1.04, respectively) or regression (adjusted-HR per log10 U/mL = 1.17, 95% CI = 0.95–1.46; adjusted-HR per log10 PEI U/mL = 0.97, 95% CI = 0.78–1.22, respectively) after adjusting for age, gender, duration of antiretroviral therapy, protease inhibitor-containing antiretroviral therapy, and CD4+/CD8+ ratio. Nevertheless, changes from the previous visit of qAnti-HBc levels were associated with liver fibrosis regression (adjusted-HR per log10 PEIU/mL change = 5.46, 95% CI = 1.56–19.16). Conclusions Baseline qHBcrAg and qAnti-HBc levels are not associated with liver fibrosis evolution in TDF-treated HIV-HBV coinfected patients. The link between changes in qAnti-HBc levels during follow-up and liver fibrosis regression merits further study., Serum quantification of hepatitis B core-related antigen and antihepatitis B core antibodies are not associated with liver fibrosis evolution in TDF-treated HIV-HBV-coinfected patients. Our findings support the need to assess other novel HBV markers to predict this clinical outcome.
Published: 2020
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31. Elevated Fatty Liver Index as a Risk Factor for All‐Cause Mortality in Human Immunodeficiency Virus–Hepatitis C Virus–Coinfected Patients (ANRS CO13 HEPAVIH Cohort Study)

Author: Firouzé Bani-Sadr, Lionel Piroth, Tangui Barré, Linda Wittkop, Marie-Laure Chaix, Teresa Rojas Rojas, Lawrence Serfaty, Fabienne Marcellin, Julie Chas, Camelia Protopopescu, Dominique Salmon-Ceron, Karine Lacombe, Laure Esterle, Olivia Zaegel, Philippe Sogni, Patrick Miailhes, Maria Patrizia Carrieri, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire Marseille, CHU Marseille, Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Hôpital universitaire Robert Debré [Reims], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Santé publique [CHU Bordeaux], CHU de bordeaux, Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [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 National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Aix Marseille Université (AMU), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Dupuis, Christine, and Service de Maladies infectieuses et tropicales [CHU Tenon]
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Cirrhosis, Hepatitis C virus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], HIV Infections, Liver transplantation, medicine.disease_cause, Gastroenterology, Antiviral Agents, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Cause of Death, medicine, Humans, Risk factor, ComputingMilieux_MISCELLANEOUS, Hepatology, business.industry, Coinfection, Hazard ratio, Fatty liver, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, Fatty Liver, [SDV] Life Sciences [q-bio], 030104 developmental biology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, Female, France, Steatosis, Viral hepatitis, business
Abstract: International audience; Background and aims: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, nonalcoholic steatohepatitis, a known risk factor for mortality. The fatty liver index (FLI), a noninvasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV-coinfected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French National Agency for Research on Aids and Viral Hepatitis CO13 HEPAVIH cohort (983 patients, 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality.Approach and results: After multiple adjustment, individuals with FLI ≥ 60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval], 1.91 [1.17-3.12], P = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], P = 0.004), advanced fibrosis (1.77 [1.00-3.14], P = 0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], P < 10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], P = 0.015), and HIV Centers for Disease Control and Prevention clinical stage C (2.88 [1.74-4.79], P < 10-3 ).Conclusions: An elevated FLI (≥60) is a risk factor for all-cause mortality in HIV-HCV-coinfected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of noninvasive steatosis biomarkers to help identify coinfected patients with higher mortality risk.
Published: 2020
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32. Life after hepatitis C cure in HIV-infected people who inject drugs and men who have sex with men treated with direct-acting antivirals in France: Health perceptions and experiences from qualitative and quantitative findings (ANRS CO13 HEPAVIH)

Author: Trevor Goodyear, Chiara Calzolaio, Fabienne Marcellin, Rod Knight, Dominique Salmon-Ceron, Linda Wittkop, Philippe Sogni, David Zucman, Jeannie Shoveller, Marion Mora, Vincent Di Beo, Isabelle Poizot-Martin, Karine Lacombe, Patrizia Carrieri, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), British Columbia Centre on Substance Use [Vancouver, BC, Canada] (BCCSU), University of British Columbia (UBC), École des hautes études en sciences sociales (EHESS), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Santé publique [CHU Bordeaux], CHU de bordeaux, Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Dupuis, Christine
Subjects: Male, medicine.medical_specialty, mixed methods, [SDV]Life Sciences [q-bio], men who have sex with men, people who inject drugs, Qualitative property, HIV Infections, DIRECT ACTING ANTIVIRALS, Antiviral Agents, Article, Men who have sex with men, 03 medical and health sciences, Sexual and Gender Minorities, 0302 clinical medicine, Mixed approach, Quality of life (healthcare), Virology, Hiv infected, medicine, HIV-HCV co-infection, Humans, 030212 general & internal medicine, Prospective Studies, Homosexuality, Male, Substance Abuse, Intravenous, direct-acting antivirals, Hepatology, business.industry, virus diseases, Hepatitis C, Hepatitis C, Chronic, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Pharmaceutical Preparations, Family medicine, Cohort, Quality of Life, 030211 gastroenterology & hepatology, Perception, business
Abstract: International audience; There remains a substantial gap in our understandings of the life experiences of patients following HCV cure among HIV-HCV-co-infected people who inject drugs (PWID) and men who have sex with men (MSM), two key populations targeted for HCV elimination. We described the experiences and perspectives of HIV-positive PWID and MSM, HCV-cured following treatment with direct-acting antivirals (DAA). We used an exploratory sequential mixed approach using both qualitative data (semi-structured interviews with 27 PWID and 20 MSM) and quantitative data (self-administered questionnaires with 89 PWID) via the prospective ANRS CO13 HEPAVIH cohort. PWID reported improvements in physical health-related quality of life (HRQL) and self-reported symptoms following treatment, but no significant change in mental HRQL. During interviews, several MSM, more recently diagnosed with HCV, expressed less concern regarding HCV than HIV infection and interpreted improvements in their overall well-being after HCV cure to be more related to a closer connection with healthcare providers than with viral elimination. By contrast, PWID, particularly those previously exposed to interferon-based treatments, described major improvements in their physical HRQL. Both MSM and PWID reported improvements in cognitive or psychological wellbeing, and a majority of them reported some degree of concern over potential HCV reinfection. To conclude, though health benefits of HCV cure concern both groups, HIV-infected PWID and MSM may have different representations and experiences following DAA treatment, related to their history with HCV. They are thus likely to benefit from holistic, post-treatment follow-up care that is responsive to their evolving health and social contexts.
Published: 2020
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33. Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in people who use injecting drugs in Senegal

Author: Nicolas Rouveau, Raoul Moh, Alain Attia, Ndèye Coumba Toure Kane, Richard Njouom, Léa Duchesne, Gilles Hejblum, Karine Lacombe, Thomas-d'Aquin Toni, Babacar Sylla, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Aristide-Le-Dantec, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Université Félix Houphouët-Boigny (UFHB), Programme PACCI, Centre Hospitalier Universitaire [Treichville] (CHU), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), CHU Yopougon [Abidjan, Cote d'Ivoire], 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), Duchesne, Léa, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Cost effectiveness, Hepatitis C virus, Cost-Benefit Analysis, Population, Medicine (miscellaneous), JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I19 - Other, medicine.disease_cause, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Environmental health, Diagnosis, Medicine, Seroprevalence, Humans, Mass Screening, 030212 general & internal medicine, education, Substance Abuse, Intravenous, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, education.field_of_study, 030505 public health, business.industry, Health Policy, Incidence (epidemiology), Cost-effectiveness analysis, Decision Trees, 1. No poverty, virus diseases, Hepatitis C, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Senegal, digestive system diseases, 3. Good health, Dried blood spot, Models, Economic, Point-of-Care Testing, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Drug users, Africa, RNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Dried Blood Spot Testing, 0305 other medical science, business
Abstract: International audience; Background: Scaling-up the access to hepatitis C virus (HCV) diagnostics for people who use injecting drugs (PWID) is essential to reduce the HCV incidence in low and middle-income countries. Methods: A decision tree model was developed to compare the cost-effectiveness of 12 strategies for diagnosing HCV in Senegal with a health sector perspective. Strategies included HCV-Ab screening and confirmation of viraemia (based on HCV-RNA or HCV core antigen detection) or only the latter step. Laboratory assays and decentralized tools (point-of-care (POC) tests and dried blood spot (DBS) samples) were included. The base-case assumed a 38.9% seroprevalence, as reported in the PWID population of Dakar. Results: Compared to the cheapest strategy (POC HCV-Ab followed by POC HCV-RNA (S5)), one strategy remained un-dominated in the base-case: POC HCV-Ab followed by venepuncture-based laboratory HCV-RNA (S3). Above a lost to follow-up testing rate of 2.3%, combining POC HCV-Ab with HCV-RNA on DBS (S4) became more cost-effective than S3. Above this threshold, a single-step POC HCV-RNA (S12) was also found un-dominated (ICER to S5=€3,297.50). S5, S12 and S4 cost €14.21, €17.03 and €36.55/screened individual. Incremental cost-effectiveness ratios (€/additional true positive case) were 2,164.82 (S12 versus S5) and 3,297.50 (S4 versus S12). Whenever HCV seroprevalence reached 55.5%, S12 became more cost-effective than S5. Moreover, S4 required a budget 2 to 2.5 times higher than S5 or S12 for diagnosing 90% of HCV-infected PWID in Dakar.Conclusion: A two-step POC-based strategy (S5) would be the most cost-effective option among those proposed in this study for diagnosing HCV in PWID in Senegal. This study illustrates how the lack of secure financing and of data on PWID in LMICs, render difficult to identify the most sustainable strategy in those countries, as well as its implementation.
Published: 2020
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34. HCV or HBV coinfection and lymphoma risk in people living with HIV

Author: Besson, Caroline, Noel, Nicolas, Lancar, Rémi, Prevot, Sophie, Algarte-Genin, Michele, Rosenthal, Eric, Bonnet, Fabrice, Meyohas, Marie-Caroline, Partisani, Marialuisa, Oberic, Lucie, Gabarre, Jean, Goujard, Cécile, Cheret, Antoine, Arvieux, Cédric, Katlama, Christine, Salmon, Dominique, Boué, François, Costello, Régis, Hendel-Chavez, Houria, Taoufik, Yassine, Fontaine, Hélène, Coppo, Paul, Mounier, Nicolas, Delobel, Pierre, Costagliola, Dominique, Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Hôpital Archet 2 [Nice] (CHU), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], 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 Strasbourg, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique et de thérapie cellulaire [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), Hôpital l'Archet, CHU Toulouse [Toulouse], Centre Hospitalier de Versailles (CHV), 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), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service des maladies infectieuses [CHU Pitié-Salêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Antoine Béclère [Clamart], Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: hepatitis C virus, Hodgkin’s lymphoma, immune system diseases, hemic and lymphatic diseases, [SDV]Life Sciences [q-bio], virus diseases, HIV infection, non-Hodgkin’s lymphoma, hepatitis B virus, digestive system diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: Chronic hepatitis C virus (HCV) and hepatitis virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era.Design: We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort.Methods: Prevalence of HCV-seropositivity and chronic HBV infections were compared to those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4).Results: Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (HL) (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 (26% versus 14%, Odd-Ratio (OR): 2.15; 95% confidence interval [1.35-3.32]) while there was no association between HL and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5% versus 7% in FHDH-ANRS-CO4 but tended to be associated with HL (prevalence of 14%, OR: 2.16 [0.98-4.27]). Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], Hazard-ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome.Conclusions: In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of HL risk.
Published: 2020
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35. Prevalence and Risk Factors of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in General Population: the French Nationwide NASH-CO Study

Author: Nabi, Oumarou, Lacombe, Karine, Boursier, Jérôme, Mathurin, Philippe, Zins, Marie, Serfaty, Lawrence, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), CHU Lille, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Hôpital de Hautepierre [Strasbourg], and NABI, Oumarou
Subjects: MESH: Aged, MESH: Middle Aged, MESH: Humans, MESH: Non-alcoholic Fatty Liver Disease, Forns Index, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Risk Assessment, MESH: Male, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Type 2 Diabetes, MESH: France, MESH: Cross-Sectional Studies, MESH: Risk Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Fatty Liver Index, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Obesity, MESH: Liver Cirrhosis, MESH: Female, MESH: Prevalence
Abstract: International audience; The burden of nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis has not been reported so far at a nationwide level in Europe. According to a meta-analysis, the prevalence of NAFLD in European countries ranged from 4% to 50%, reflecting the heterogeneity of study populations. 1 The French CONSTANCES population-based cohort was designed as a large representative sample for age, gender, and socioeconomic status of the French adult population. 2 The present study was aimed to assess the prevalence of NAFLD and advanced fibrosis in the CONSTANCES cohort by using noninvasive markers, and to examine risk factors associated with these conditions.
Published: 2020
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36. Model-based cost-effectiveness estimates of testing strategies for diagnosing hepatitis C virus infection in Central and Western Africa

Author: Léa Duchesne, Coumba Toure Kane, Karine Lacombe, Babacar Sylla, Raoul Moh, Gilles Hejblum, Richard Njouom, Alain Attia, Nicolas Rouveau, Thomas d. 'Aquin Toni, 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 Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Hôpital Aristide-Le-Dantec, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Programme PAC-CI, ANRS France Recherche Nord & sud Sida-hiv hépatites, Université Félix Houphouët-Boigny (UFHB), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], 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: RNA viruses, Viral Diseases, Time Factors, Economics, Cost effectiveness, Cost-Benefit Analysis, Social Sciences, Hepacivirus, Economic Geography, medicine.disease_cause, Biochemistry, Medical Conditions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Nucleic Acids, Medicine, 030212 general & internal medicine, Dried blood, Pathology and laboratory medicine, Virus Testing, Multidisciplinary, Geography, Hepatitis C virus, virus diseases, Cost-effectiveness analysis, Medical microbiology, Hepatitis C, 3. Good health, Africa, Western, Infectious Diseases, Point-of-Care Testing, Viruses, Low and Middle Income Countries, 030211 gastroenterology & hepatology, Pathogens, Research Article, medicine.medical_specialty, Science, Cost-Effectiveness Analysis, Microbiology, 03 medical and health sciences, Health Economics, Diagnostic Medicine, Environmental health, Humans, Seroprevalence, Africa, Central, Viremia, Medicine and health sciences, Models, Statistical, Health economics, Biology and life sciences, Flaviviruses, business.industry, Public health, Decision Trees, Organisms, Viral pathogens, Hepatitis viruses, Economic Analysis, Hcv elimination, digestive system diseases, Microbial pathogens, Health Care, Earth Sciences, RNA, Feasibility Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundWhereas 72% of hepatitis C virus (HCV)-infected people worldwide live in low- and middle-income countries (LMICs), only 6% of them have been diagnosed. Innovative technologies for HCV diagnosis provide opportunities for developing testing strategies more adapted to resource-constrained settings. However, studies about their economic feasibility in LMICs are lacking.MethodsAdopting a health sector perspective in Cameroon, Cote-d'Ivoire, and Senegal, a decision tree model was developed to compare 12 testing strategies with the following characteristics: a one-step or two-step testing sequence, HCV-RNA or HCV core antigen as confirmative biomarker, laboratory or point-of-care (POC) tests, and venous blood samples or dried blood spots (DBS). Outcomes measures were the number of true positives (TPs), cost per screened individual, incremental cost-effectiveness ratios, and nationwide budget. Corresponding time horizon was immediate, and outcomes were accordingly not discounted. Detailed sensitivity analyses were conducted.FindingsIn the base-case, a two-step POC-based strategy including anti-HCV antibody (HCV-Ab) and HCV-RNA testing had the lowest cost, €8.18 per screened individual. Assuming a lost-to-follow-up rate after screening > 1.9%, a DBS-based laboratory HCV-RNA after HCV-Ab POC testing was the single un-dominated strategy, requiring an additional cost of €3653.56 per additional TP detected. Both strategies would require 8-25% of the annual public health expenditure of the study countries for diagnosing 30% of HCV-infected individuals. Assuming a seroprevalence > 46.9% or a cost of POC HCV-RNA < €7.32, a one-step strategy based on POC HCV-RNA dominated the two-step POC-based strategy but resulted in many more false-positive cases.ConclusionsPOC HCV-Ab followed by either POC- or DBS-based HCV-RNA testing would be the most cost-effective strategies in the study countries. Without a substantial increase in funding for health or a dramatic decrease in assay prices, HCV testing would constitute an economic barrier to the implementation of HCV elimination programs in LMICs.
Published: 2020
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37. Serum tryptophan-derived quinolinate and indole-3-acetate are associated with carotid intima-media thickness and its evolution in HIV-infected treated adults

Author: Brigitte Autran, Ariel Cohen, Jean-Philippe Bastard, Soraya Fellahi, Anders Boyd, Jean-Luc Meynard, Pierre-Marie Girard, Delphine Sauce, Assia Samri, Nabila Haddour, Jacqueline Capeau, Franck Boccara, Farid Ichou, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), and Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: 0301 basic medicine, medicine.medical_specialty, carotid intima-media thickness, [SDV]Life Sciences [q-bio], Metabolite, antiretroviral, 030106 microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, cardiovascular disease, Internal medicine, Major Article, Medicine, cardiovascular diseases, 030212 general & internal medicine, tryptophan metabolism, ComputingMilieux_MISCELLANEOUS, business.industry, Catabolism, Tryptophan, HIV, metabolomics, Quinolinate, Uridine, Fold change, 3. Good health, Infectious Diseases, Endocrinology, Oncology, chemistry, Intima-media thickness, cardiovascular system, business, Kynurenine
Abstract: Background HIV-infected individuals undergoing effective antiretroviral therapy (ART) present an increased risk of atherosclerotic cardiovascular disease. We identified serum metabolites associated with carotid intima-media-thickness (c-IMT) and its evolution. Methods 143 hydrophilic serum metabolites were measured by ultra-performance-liquid-chromatography coupled to high-resolution mass-spectrometry in 49 HIV+ART+, 48 HIV+ART-naïve, and 50 HIV-negative age-matched, never-smoking, male triads. Metabolites differentially altered between groups (“features”) were defined as having a Benjamini-Hochberg adjusted p-value 0.25 log2 absolute mean fold-change in metabolite levels. c-IMT was measured across 12 sites at inclusion in all individuals and at the carotid-artery (cca) after a median 5.1 years in 32 HIV+ART+ individuals. Difference in c-IMT (cross-sectional analysis) and slope of cca-IMT regression/progression per year (longitudinal analysis) for each log10(area) increase in metabolite level was estimated with linear regression. Results Compared to HIV-, metabolite features of HIV+ART+ were increased N6,N6,N6-trimethyl-L-lysine and decreased ferulate and 5-hydroxy-L-tryptophan; while features of HIV+ART-naïve were increased malate, kynurenine, 2-oxoglutarate, and indole-3-acetate and decreased succinate and 5-hydroxy-L-tryptophan. In HIV+ART+ individuals, quinolinate and/or indole-3-acetate were positively associated with c-IMT (p Conclusion In these highly-selected HIV-positive ART-controlled males, two novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression.
Published: 2019
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38. Control of Low-Density Lipoprotein Cholesterol in Secondary Prevention of Coronary Artery Disease in Real-Life Practice: The DAUSSET Study in French Cardiologists

Author: Jean Ferrières, François Roubille, Michel Farnier, Patrick Jourdain, Denis Angoulvant, Franck Boccara, Nicolas Danchin, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l’immunodéficience humaine (GRC22 C²MV), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Service des maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU)-Sorbonne Université (SU)-Service de cardiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: myocardial infarction, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, hypercholesterolemia, dyslipidemia, coronary artery disease, secondary prevention, guidelines adherence, Medicine, lipids (amino acids, peptides, and proteins), General Medicine, Article
Abstract: International audience; Introduction: Patients with established coronary artery disease (CAD) are at very high risk for cardiovascular events.Methods: The DAUSSET study is a national, multicenter, non-interventional study that included very high-risk CAD patients followed by French cardiologists. It aimed to describe real-life clinical practices for low-density lipoprotein (LDL) cholesterol control in the secondary prevention of CAD.Results: A total of 912 patients (mean age, 65.4 years; men, 76.1%; myocardial infarction, 69.4%; first episode, 80.1%) were analyzed. The LDL cholesterol goal was 70 mg/dL in most cases (84.9%). The LDL cholesterol goal
Published: 2021
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39. Trends in asymptomatic STI among HIV-positive MSM and lessons for systematic screening

Author: Eric Farfour, Svetlane Dimi, Olivier Chassany, Sébastien Fouéré, Nadia Valin, Julie Timsit, Jade Ghosn, Claudine Duvivier, Martin Duracinsky, David Zucman, DRIVER study group, HAL-SU, Gestionnaire, Hôpital Foch [Suresnes], Centre de Vaccinations internationales Air-France, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), 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), 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), 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 des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Male, Bacterial Diseases, RNA viruses, Physiology, Gastroenterology and hepatology, Gonorrhea, Chlamydia trachomatis, HIV Infections, Urine, Pathology and Laboratory Medicine, Treponematoses, Geographical locations, Hepatitis, Serology, Sexual and Gender Minorities, Medical Conditions, 0302 clinical medicine, Immunodeficiency Viruses, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV Seropositivity, Medicine and Health Sciences, Mass Screening, 030212 general & internal medicine, Doxycycline, 0303 health sciences, Multidisciplinary, Chlamydia, Transmission (medicine), virus diseases, Middle Aged, Hepatitis A, Hepatitis B, Body Fluids, 3. Good health, Europe, Infectious hepatitis, Infectious Diseases, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, France, Pathogens, Anatomy, medicine.symptom, Research Article, Neglected Tropical Diseases, medicine.drug, Adult, medicine.medical_specialty, Science, Urology, HIV prevention, Sexually Transmitted Diseases, Men WHO Have Sex with Men, Viral diseases, Microbiology, Asymptomatic, 03 medical and health sciences, Internal medicine, Retroviruses, medicine, Humans, Syphilis, European Union, Microbial Pathogens, Liver diseases, Preventive medicine, Genitourinary Infections, 030306 microbiology, business.industry, Lentivirus, Organisms, HIV, Biology and Life Sciences, Chlamydia Infections, Tropical Diseases, medicine.disease, Neisseria gonorrhoeae, Medical risk factors, Public and occupational health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Population Groupings, business, Sexuality Groupings
Abstract: International audience; The burden of STIs is particularly high in HIV-infected MSM patients. A recent increase in STIs prevalence has been noticed in the US and western European countries. We aim to assess trends in asymptomatic STIs following the publication of recommendations for STIs screening, i.e. Chlamydia (CT) and gonorrhea (NG). Seventeen centers located in the Paris area participated in the study. All asymptomatic HIV-infected MSM patients attending a follow up consultation were proposed to participated in the study. Asymptomatic patients were included over 2 periods: period 1 from April to December 2015 and period 2 from September to December 2017. Etiologic diagnosis of STIs including hepatitis B, C, syphilis, was performed using a serological test, including a non-treponemal titer with a confirmatory treponemal assay for syphilis. CT and NG were screened using a nucleic acid amplification test (NAATs) on 3 anatomical sites, i.e. urine, rectal and pharyngeal. Overall, 781 patients were included: 490 and 291 in periods 1 and 2 respectively. Asymptomatic CT, NG, and syphilis were diagnosed in 7.5%, 4.8% and, 4.2% respectively. The rate of patients having a multisite asymptomatic infection was 10.2% and 21.1% for CT and NG respectively. The most frequently involved anatomical sites for CT and NG asymptomatic infections were anorectal (66.1% and 55.2% respectively) and pharyngeal (47.4% and 60.5% respectively). CT and NG asymptomatic infection increased by 1.3- and 2-fold respectively between the two periods while syphilis decreased by 3 folds. Our results encourage to reconsider multisite screening for CT and NG in asymptomatic HIV positive MSM as the yield of screening urinary samples only might be low. Despite the more systematic STI screening of asymptomatic HIV positive MSM the prevalence of STI is increasing in MSM in France. Therefore, this strategy has not led to alter CT and NG transmission. The decrease of syphilis might involve self-medication by doxycycline, and the intensification of syphilis screening.
Published: 2021
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40. Uptake of Tenofovir-Based Antiretroviral Therapy among HIV–HBV-Coinfected Patients in the EuroSIDA Study

Author: Jens D Lundgren, Anna Lisa Ridolfo, Jelena Smidt, Elena Kuzovatova, Stéphane De Wit, Roxana Radoi, Santiago Moreno, Djordje Jevtovic, Vesnadarjan Haziosmanovic, Helen Sambatakou, Lars Peters, Jose Zapirain, Amanda Mocroft, Chloe Orkin, Daniel Grint, Anna Grzeszczuk, Jürgen K. Rockstroh, Igor Karpov, Alexandra Calmy, Karine Lacombe, Magnus Gottfredsson, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University College of London [London] (UCL), London School of Hygiene and Tropical Medicine (LSHTM), Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Hippokration General Hospital, University of Athens Medical School [Athens], 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Pierre, Universitätsklinikum Bonn (UKB), Belarus State Medical University, University of Bialystok, Clinical Center University of Sarajevo, UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Victor Babeş University of Medicine and Pharmacy (UMFT), National Research Lobachevsky State University of Nizhny Novgorod (UNN), Royal London Hospital, Ospedale L. Sacco, IT University of Copenhagen (ITU), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, 0301 basic medicine, HBsAg, [SDV]Life Sciences [q-bio], HIV Infections, Polyethylene Glycols, immune system diseases, Antiretroviral Therapy, Highly Active, Adefovir, Medicine, Pharmacology (medical), Prospective Studies, Coinfection, virus diseases, Entecavir, Middle Aged, Hepatitis B, Recombinant Proteins, Europe, [SDV] Life Sciences [q-bio], Infectious Diseases, Anti-Retroviral Agents, Lamivudine, Practice Guidelines as Topic, Female, medicine.drug, Adult, Cart, Hepatitis B virus, medicine.medical_specialty, Guanine, 030106 microbiology, Organophosphonates, Lower risk, 03 medical and health sciences, Hepatitis B, Chronic, Internal medicine, Drug Resistance, Viral, Humans, Tenofovir, Adverse effect, Pharmacology, Hepatitis B Surface Antigens, business.industry, Adenine, HIV, Interferon-alpha, medicine.disease, Drug Utilization, CD4 Lymphocyte Count, Discontinuation, DNA, Viral, business
Abstract: Background According to guidelines all HIV–HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV–HBV patients in the EuroSIDA study. Methods All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. Results 953 HIV–HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count 3 decreased from 85% to 52% in the periods 2002–2006 to 2007–2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events ( n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. Conclusions Although use of tenofovir-based cART among HIV–HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
Published: 2017
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41. Statin therapy and low-density lipoprotein cholesterol reduction in HIV-infected individuals after acute coronary syndrome: Results from the PACS-HIV lipids substudy

Author: Marguerite Guiguet, Ariel Cohen, Pierre-Marie Girard, Emmanuel Teiger, Sylvie Lang, Christian Funck-Brentano, Philippe Gabriel Steg, Murielle Mary-Krause, Franck Boccara, Dominique Costagliola, Joe Miantezila Basilua, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Cardiologie [Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials (FACT), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), 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), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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], Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe de REcherche en Cardio Oncologie (GRC 27 - GRECO), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Pitié-Salpêtrière [AP-HP], Service de Cardiologie [CHU Saint-Antoine], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Groupe de REcherche en Cardio Oncologie [CHU Saint-Antoine] (GRC 27 GRECO), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN]
Subjects: Adult, Male, Acute coronary syndrome, medicine.medical_specialty, Statin, medicine.drug_class, [SDV]Life Sciences [q-bio], Low density lipoprotein cholesterol, HIV Infections, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Acute Coronary Syndrome, Prospective cohort study, National Cholesterol Education Program, Aged, business.industry, Cholesterol, Cholesterol, LDL, Middle Aged, medicine.disease, Lipids, Endocrinology, chemistry, Multicenter study, Female, lipids (amino acids, peptides, and proteins), Observational study, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business
Abstract: Knowledge about lipid interventions in secondary prevention in HIV-infected individuals is limited; studies are sparse.A prospective observational multicenter study enrolled 282 patients on statin 1 month after first acute coronary syndrome (ACS) (95 HIV-infected individuals, 187 HIV-uninfected). Data on fasting lipids (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], non-HDL-C, triglycerides, TC/HDL-C ratio) were collected over 3 years. The evolution of lipid concentrations was analyzed using mixed-effects models. Achievement of National Cholesterol Education Program Adult Treatment Panel III lipid goals and prescribed statin intensity was assessed.Mean age of patients was 49.0 years, and 94% were men. Baseline lipids were similar in the 2 groups. Six months after first ACS, less low-density lipoprotein cholesterol reduction was observed in the HIV-infected GROUP (adjusted mean change -10.13; 95% CI -20.63 to 0.37; P=.06) than in the HIV-uninfected group (Adjusted mean change -38.51; 95% CI -46.00 to -31.04; P.0001) Similar trends were observed for TC and non-HDL-C. After ACS, initial statin prescription for HIV-infected compared with HIV-uninfected individuals was more frequently a moderate-intensity statin (66% vs 45%) and less frequently a high-intensity statin (15% vs 45%). Over 3 years of follow-up, the proportion of HIV-infected patients receiving high-intensity statin remained persistently lower than the proportion observed in the HIV-uninfected group.In this observational study, HIV-infected individuals after first ACS exhibited worse lipid profiles than controls particularly during the first 6 months while receiving less potent statins. Appropriate statin intensity should be prescribed in HIV-infected individuals with awareness of potential drug-drug interactions.
Published: 2017
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42. Infection par le virus de l'hépatite B : histoire naturelle, manifestations cliniques et principes thérapeutiques

Author: Paccoud, Olivier, Surgers, Laure, Lacombe, Karine, 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), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Épidémiologie, Histoire naturelle, antivirals, natural history, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiviraux, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, hepatitis B virus, Virus de l’hépatite B
Abstract: International audience; Chronic hepatitis B infection remains a major public-health problem, with approximately 260 million world-wide cases of infection. Recent advances in the understanding of the natural history of chronic hepatitis B infection have led to progress in the care of infected patients. Sustained viral suppression is now possible for a majority of treated patients and is associated with a decrease in the morbidity and mortality attributable to cirrhosis and hepatocellular carcinoma. Complete cure is however not yet possible, due to the long-term persistence of viral DNA in hepatocytes of treated patients. Assessing the risk of viral reactivation in patients receiving immunosuppressive therapy is an increasingly frequent situation in clinical practice and its management is guided by both the patient's serological status and the potency of the immunosuppressive regimen. This review aims to present the clinical and biological presentations of chronic hepatitis B infection, the modalities of antiviral treatment, and how to assess the risk of viral reactivation in patients receiving immunosuppressive therapy.; Avec près de 260 millions de cas dans le monde, l’hépatite B chronique est la première cause de mortalité par maladie du foie et dépasse actuellement l’infection par le VIH, la tuberculose ou le paludisme en termes de morbi-mortalité. D’importants progrès dans la compréhension de l’histoire naturelle de l’infection chronique ont conduit à une optimisation des modalités de suivi et des thérapeutiques proposées aux patients infectés. L’arsenal thérapeutique actuellement disponible permet d’obtenir dans la majorité des cas une suppression virale suffisante pour réduire le risque de complications hépatiques liées à l’infection chronique. La guérison complète n’est cependant pas encore possible, du fait de la persistance d’ADN viral dans les hépatocytes du sujet infecté, qui expose au risque de réactivation à l’arrêt du traitement. La gestion de ce risque sous traitement immunosuppresseur, qui dépend à la fois du statut sérologique et du traitement utilisé, est une situation fréquente et importante en pratique clinique, qui a fait l’objet de recommandations récentes.Cette revue générale propose de décrire les manifestations cliniques et biologiques de l’infection par le virus de l’hépatite B, les indications et modalités du traitement antiviral, et de résumer les principes de prise en charge du risque de réactivation virale sous traitement immunosuppresseur.
Published: 2019
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43. Infection par le virus de l'hépatite B : histoire naturelle, manifestations cliniques et principes thérapeutiques

Author: O. Paccoud, Laure Surgers, Karine Lacombe, 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), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Cirrhosis, Antiviraux, Serology, 03 medical and health sciences, 0302 clinical medicine, antivirals, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal Medicine, medicine, Potency, In patient, Viral suppression, Dna viral, Histoire naturelle, business.industry, Gastroenterology, medicine.disease, 3. Good health, Natural history, Épidémiologie, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, natural history, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, hepatitis B virus, Virus de l’hépatite B
Abstract: Chronic hepatitis B infection remains a major public-health problem, with approximately 260 million world-wide cases of infection. Recent advances in the understanding of the natural history of chronic hepatitis B infection have led to progress in the care of infected patients. Sustained viral suppression is now possible for a majority of treated patients and is associated with a decrease in the morbidity and mortality attributable to cirrhosis and hepatocellular carcinoma. Complete cure is however not yet possible, due to the long-term persistence of viral DNA in hepatocytes of treated patients. Assessing the risk of viral reactivation in patients receiving immunosuppressive therapy is an increasingly frequent situation in clinical practice and its management is guided by both the patient's serological status and the potency of the immunosuppressive regimen. This review aims to present the clinical and biological presentations of chronic hepatitis B infection, the modalities of antiviral treatment, and how to assess the risk of viral reactivation in patients receiving immunosuppressive therapy., Avec près de 260 millions de cas dans le monde, l’hépatite B chronique est la première cause de mortalité par maladie du foie et dépasse actuellement l’infection par le VIH, la tuberculose ou le paludisme en termes de morbi-mortalité. D’importants progrès dans la compréhension de l’histoire naturelle de l’infection chronique ont conduit à une optimisation des modalités de suivi et des thérapeutiques proposées aux patients infectés. L’arsenal thérapeutique actuellement disponible permet d’obtenir dans la majorité des cas une suppression virale suffisante pour réduire le risque de complications hépatiques liées à l’infection chronique. La guérison complète n’est cependant pas encore possible, du fait de la persistance d’ADN viral dans les hépatocytes du sujet infecté, qui expose au risque de réactivation à l’arrêt du traitement. La gestion de ce risque sous traitement immunosuppresseur, qui dépend à la fois du statut sérologique et du traitement utilisé, est une situation fréquente et importante en pratique clinique, qui a fait l’objet de recommandations récentes.Cette revue générale propose de décrire les manifestations cliniques et biologiques de l’infection par le virus de l’hépatite B, les indications et modalités du traitement antiviral, et de résumer les principes de prise en charge du risque de réactivation virale sous traitement immunosuppresseur.
Published: 2019
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44. Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM

Author: Yazdan Yazdanpanah, Lionel Piroth, Pierre-Marie Girard, Julie Chas, Eric Rosenthal, Stéphane Chevaliez, Hayette Rougier, Gilles Pialoux, Karine Lacombe, Anders Boyd, Marc-Antoine Valantin, Patrick Miailhes, Gilles Peytavin, 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 Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [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), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], 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), Hôpital l'Archet, 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 Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: hepatitis C virus, Cyclopropanes, Male, adverse event, men who have sex with men, Hepacivirus, medicine.disease_cause, Sexual and Gender Minorities, blood HIV RNA, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, follow-up, Clinical endpoint, Medicine, Pharmacology (medical), infections, 030212 general & internal medicine, hepatitis c, education.field_of_study, Sulfonamides, hepatitis c rna, Imidazoles, virus diseases, Hepatitis C, virology, hepatitis C virus genotype 1, 3. Good health, Europe, Infectious Diseases, Grazoprevir, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Microbiology (medical), medicine.medical_specialty, Elbasvir, Genotype, Hepatitis C virus, Population, elbasvir, Antiviral Agents, reinfection, 03 medical and health sciences, Internal medicine, Quinoxalines, Humans, Homosexuality, Male, Adverse effect, education, plasma, suicide, Benzofurans, Pharmacology, business.industry, Surrogate endpoint, HIV, grazoprevir, Hepatitis C, Chronic, medicine.disease, Amides, surrogate endpoints, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Quality of Life, Carbamates, business
Abstract: Background In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. Patients and methods In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection. Results In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%–99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients. Conclusions Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.
Published: 2019
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45. Sleep disturbances in HIV-HCV coinfected patients: indications for clinical management in the HCV cure era (ANRS CO13 HEPAVIH cohort)

Author: Dominique Salmon-Ceron, Maria Patrizia Carrieri, Fabienne Marcellin, Linda Wittkop, Marie Costa, Philippe Sogni, Issifou Yaya, Denis Lacoste, Hugues Aumaitre, Jessica Krause, Virginie Villes, Teresa Rojas Rojas, Camelia Protopopescu, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Coordination Régionale de la lutte contre l'infection à VIH (COREVIH Aquitaine), CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin-Hôpital du Tondu, Service des maladies infectieuses [CH Perpignan], Centre Hospitalier Saint Jean de Perpignan, Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), CHU Bordeaux [Bordeaux], 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), Université Paris Descartes - Paris 5 (UPD5), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the French National Agency for Research on Aids and Viral Hepatitis (ANRS: France Recherche Nord & sud Sida-hiv Hépatites), with the participation of Abbott France, Glaxo-Smith-Kline, Roche, Schering-Plough, BMS, Merck-Serono., ANRS CO13 HEPAVIH Study Group : Scientific Committee of the ANRS CO13 HEPAVIH Study Group: D. Salmon (co-Principal investigator), L. Wittkop (co- Principal Investigator), P. Sogni (co-Principal Investigator), L. Esterle (project manager), P. Trimoulet, J. Izopet, L. Serfaty, V. Paradis, B. Spire, P. Carrieri, M.A. Valantin, G. Pialoux, J. Chas, I. Poizot-Martin, K. Barange, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Vittecoq, D. Neau, P. Morlat, F. Bani-Sadr, L. Meyer, F. Boufassa, B. Autran, A.M. Roque, C. Solas, H. Fontaine, D. Costagliola, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaître, D. Rey, G. Peytavin, V. Petrov-Sanchez, A. Pailhé. Clinical Centres (ward/participating physicians): APHP Cochin, Paris (Médecine Interne et Maladies Infectieuses: D. Salmon, R. Usubillaga, Hépato-gastro-entérologie: P. Sogni, Anatomo-pathologie: B. Terris, Virologie: P. Tremeaux), APHP Pitié-Salpétrière, Paris (Maladies Infectieuses et Tropicales: C. Katlama, M.A. Valantin, H. Stitou, Hépato-gastro-entérologie: Y. Benhamou, Anatomo-pathologie: F. Charlotte, Virologie: S. Fourati), APHP Pitié-Salpétrière, Paris (Médecine Interne: A. Simon, P. Cacoub, S. Nafissa), APHM Sainte- Marguerite, Marseille (Service d’Immuno-Hématologie Clinique: I. Poizot-Martin, O. Zaegel, H. Laroche, Virologie: C. Tamalet), APHP Tenon, Paris (Maladies Infectieuses et Tropicales: G. Pialoux, J. Chas, Anatomo-pathologie: P. Callard, F. Bendjaballah, Virologie: C. Le Pendeven), CHU Purpan, Toulouse (Maladies Infectieuses et Tropicales: B. Marchou, Hépato-gastro-entérologie: L. Alric, K. Barange, S. Metivier, Anatomo-pathologie: J. Selves, Virologie: F. Larroquette), CHU Archet, Nice (Médecine Interne: E. Rosenthal, Infectiologie: A. Naqvi, V. Rio, Anatomo-pathologie: J. Haudebourg, M.C. Saint-Paul, Virologie: C. Partouche), APHP Avicenne, Bobigny (Médecine Interne – Unité VIH: O. Bouchaud, Anatomo-pathologie: M. Ziol, Virologie: Y. Baazia), Hôpital Joseph Ducuing, Toulouse (Médecine Interne: M. Uzan, A. Bicart-See, D. Garipuy, M.J. Ferro-Collados, Virologie: F. Nicot), APHP Bichat-Claude Bernard, Paris (Maladies Infectieuses:, A. Gervais, Y. Yazdanpanah, Anatomo-pathologie: H. Adle- Biassette, Virologie: G. Alexandre), APHP Saint-Louis, Paris (Maladies infectieuses: C. Lascoux-Combe, J.M. Molina, Anatomo-pathologie: P. Bertheau, Virologie: M.L. Chaix, C. Delaugerre, S. Maylin), APHP Saint-Antoine (Maladies Infectieuses et Tropicales:, K. Lacombe, J. Bottero, J. Krause P.M. Girard, Anatomo-pathologie: D. Wendum, P. Cervera, J. Adam, Virologie: C. Viala), APHP Bicêtre, Paris (Médecine Interne: C. Goujard, Y. Quertainmont, E. Teicher, Virologie: C. Pallier, Maladies Infectieuses: D. Vittecoq), APHP Necker, Paris (Maladies Infectieuses et Tropicales: O. Lortholary, C. Duvivier, C. Rouzaud, J. Lourenco, F. Touam, C. Louisin: Virologie: V. Avettand-Fenoel, A. Mélard), CHU Pellegrin, Bordeaux (Maladies Infectieuses et Tropicales: D. Neau, A. Ochoa, E. Blanchard, S. Castet-Lafarie, C. Cazanave, D. Malvy, M. Dupon, H. Dutronc, F. Dauchy, L. Lacaze-Buzy, Anatomopathologie: P. Bioulac-Sage, Virologie: P. Trimoulet, S. Reigadas), Hôpital Saint-André, Bordeaux (Médecine Interne et Maladies Infectieuses: Médecine Interne et Maladies Infectieuses: P. Morlat, D. Lacoste, F. Bonnet, N. Bernard, M. Hessamfar, J.F. Paccalin, C. Martell, M.C. Pertusa, M. Vandenhende, P. Merciéer, D. Malvy, T. Pistone, M.C. Receveur, M. Méchain, P. Duffau, C Rivoisy, I. Faure, S. Caldato, Anatomo-pathologie: P. Bioulac-Sage, Hôpital du Haut-Levêque, Bordeaux (Médecine Interne: J.L. Pellegrin, J.F. Viallard, E. Lazzaro, C. Greib, Hôpital FOCH, Suresnes (Médecine Interne: D. Zucman, C. Majerholc, Virologie: E. Farfour), APHP Antoine Béclère, Clamart (Médecine Interne: F. Boué, J. Polo Devoto, I. Kansau, V. Chambrin, C. Pignon, L. Berroukeche, R. Fior, V. Martinez, Virologie: C. Deback), CHU Henri Mondor, Créteil (Immunologie Clinique: Y. Lévy, S. Dominguez, J.D. Lelièvre, A.S. Lascaux, G. Melica), CHU Hôtel Dieu, Nantes (Maladies Infectieuses et Tropicales: E. Billaud, F. Raffi, C. Allavena , V. Reliquet, D. Boutoille, C. Biron, Virologie: A. Rodallec, L. Le Guen), Hôpital de la Croix Rousse, Lyon (Maladies Infectieuses et Tropicales: P. Miailhes, D. Peyramond, C. Chidiac, F. Ader, F. Biron, A. Boibieux, L. Cotte, T. Ferry, T. Perpoint, J. Koffi, F. Zoulim, F. Bailly, P. Lack, M. Maynard, S. Radenne, M. Amiri, Virologie: C. Scholtes, T.T. Le-Thi), CHU Dijon, Dijon (Département d’infectiologie: L. Piroth, P. Chavanet M. Duong Van Huyen, M. Buisson, A. Waldner-Combernoux, S. Mahy, R. Binois, A.L. Simonet-Lann, D. Croisier-Bertin), CH Perpignan, Perpignan (Maladies infectieuses et tropicales: H. Aumaître), CHU Robert Debré, Reims (Médecine interne, maladies infectieuses et immunologie clinique: F. Bani-Sadr, D. Lambert, Y. Nguyen, J.L. Berger), CHRU Strasbourg (Le Trait d’Union: D. Rey, M. Partisani, M.L. Batard, C. Cheneau, M. Priester, C. Bernard- Henry, E. de Mautort, Virologie: P. Gantner et S. Fafi-Kremer), APHP Bichat-Claude Bernard (Pharmacologie: G. Peytavin). Data collection: F. Roustant, I. Kmiec, L. Traore, S. Lepuil, S. Parlier, V. Sicart-Payssan, E. Bedel, F. Touam, C. Louisin, M. Mole, C. Bolliot, M. Mebarki, A. Adda-Lievin, F.Z. Makhoukhi, O. Braik, R. Bayoud, M.P. Pietri, V. Le Baut, D. Bornarel, C. Chesnel, D. Beniken, M. Pauchard, S. Akel, S. Caldato, C. Lions, L. Chalal, Z. Julia, H. Hue, A. Soria, M. Cavellec, S. Breau, A. Joulie, P. Fisher, C. Ondo Eyene, S. Ogoudjobi, C. Brochier, V. Thoirain-Galvan. Management, statistical analyses: E. Boerg, P. Carrieri, V. Conte, L. Dequae- Merchadou,M.Desvallees, N. Douiri, L. Esterle, C. Gilbert, S. Gillet, R. Knight, F. Marcellin, L. Michel, M. Mora, C. Protopopescu, P. Roux, B. Spire, S. Tezkratt, I. Yaya, T. Barré, T. Rojas, V. Villes, M. Baudoin, M. Santos., Dupuis, Christine, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Sleep Wake Disorders, medicine.medical_specialty, Longitudinal study, Time Factors, Hepatitis C virus, Population, Human immunodeficiency virus (HIV), HIV Infections, Hepacivirus, medicine.disease_cause, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Medicine, Humans, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Hepatology, Cognitive Behavioral Therapy, business.industry, Gastroenterology, virus diseases, HIV, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, Middle Aged, Sleep in non-human animals, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Quality of Life, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; OBJECTIVES:Although common among patients coinfected with HIV and hepatitis C virus (HCV), sleep disturbances (SD) are still poorly documented in this population in the HCV cure era. This longitudinal study aimed at analysing SD in HIV-HCV coinfected patients and identifying their clinical and sociobehavioural correlates.METHODS:We used 5-year annual follow-up data from 1047 participants in the French National Agency for Research on Aids and Viral Hepatitis Cohort 13 'Hépatite et VIH' (ANRS CO13 HEPAVIH) cohort of HIV-HCV coinfected patients to identify clinical (medical records) and behavioural (self-administered questionnaires) correlates of SD (mixed-effects logistic regression). SD were identified using one item documenting the occurrence of insomnia or difficulty falling asleep (ANRS 'Action Coordonnée 24' self-reported symptoms checklist), and two items documenting perceived sleep quality (Center for Epidemiologic Studies Depression and WHO Quality of Life HIV-specific brief scales).RESULTS:Seven hundred and sixteen (68.4%) patients with completed self-administered questionnaires reported SD at their most recent follow-up visit. In the multivariable model, hazardous alcohol consumption (Alcohol Use Disorders Identification Test-Consumption score≥4 for men, ≥3 for women) (adjusted odds ratio=1.61; 95% confidence interval: 1.09-2.36), depressive symptoms (6.78; 4.36-10.55) and the number of other physical and psychological self-reported symptoms (1.10; 1.07-1.13) were associated independently with SD after adjustment for sex, age and employment status. HCV cure was not associated significantly with SD.CONCLUSION:SD remain frequent in HIV-HCV coinfected patients and are associated with a series of modifiable behavioural risk factors. Independent of HCV cure, improved screening and comprehensive management of alcohol use, physical and psychological self-reported symptoms and depression are essential in this population. Closer investigation of these risk factors of SDs may both increase sleep quality and indirectly improve patients' clinical outcomes.
Published: 2019
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46. E-health. Patterns of use and perceived benefits and barriers among people living with HIV (PLHIV) and their physicians - Part 3: Telemedicine and collection of computerized personal information

Author: Pierre Dellamonica, C. Lambert, Roxana Ologeanu-Taddei, Christine Jacomet, J. Prouteau, F. Linard, P. Bastiani, Service des maladies infectieuses et tropicales, 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), 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), Montpellier Recherche en Economie (MRE), and Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Telemedicine, Attitude of Health Personnel, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, 03 medical and health sciences, Physicians, Surveys and Questionnaires, medicine, eHealth, Electronic Health Records, Humans, Medical prescription, Aged, 0303 health sciences, Data collection, 030306 microbiology, business.industry, Middle Aged, 3. Good health, Infectious Diseases, Social deprivation, Health Records, Personal, Family medicine, Observational study, Female, business, Personally identifiable information, Attitude to Health, Facilities and Services Utilization
Abstract: Objectives To evaluate the patterns of use and perceived benefits and barriers among people living with HIV and their physicians concerning telemedicine and the collection of computerized personal information. Methods Multicenter online observational survey from October 15 to 19, 2018. Results Study participation was accepted by 229 physicians and 838/1,377 PLHIV followed in 46 centers, of which 325 (39%) responded online. We found that while 226/302 (75%) PLHIV accept online prescription renewals and 197/302 (65%) accept online medical certificates, 182/302 (60%) PLHIV − who were more often in material/social deprivation (OR = 1.70 ± 0.45; P = 0.045), less often born in Ile-de-France (OR = 0.43 ± 0.15; P = 0.018), with lower CD4 T-cell counts (OR = 0.999 ± 0.0004; P = 0.038), and less often on psychiatric treatment (OR = 0.50 ± 0.18; P = 0.047) − were receptive to teleconsultations. However, 137/225 (61%) physicians would be uncomfortable teleconsulting due to inadequate data security without it reducing the number of consultations or offering economic benefit. Asked about collection of computerized personal information, 197/296 (67%) PLHIV and 139/223 (62%) physicians agreed it improved quality of care, but 144 (49%) PLHIV and 94/222 (42%) physicians thought it was not sufficiently framed by the law. eHealth was seen as improving coordination between health professionals by 240/296 (81%) PLHIV and seen as a good thing by 181/225 (81%) physicians. Conclusion More than half of PLHIV were ready for telemedicine. PLHIV and physicians endorsed the advantage of e-health in terms of better coordination across health professionals but mistrust the data collection factor, which warrants either clarification or stronger legal protections.
Published: 2019
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47. INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

Author: Christine Katlama, Sidonie Lambert-Niclot, Marc Wirden, Laurence Morand-Joubert, Romain Palich, D. B. Fofana, Anders Boyd, Vincent Calvez, Rachid Agher, Jean-Luc Meynard, Pierre-Marie Girard, Nadia Valin, Anne-Geneviève Marcelin, Marc-Antoine Valantin, Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Subjects: 0301 basic medicine, initiation antiretroviral therapy, medicine.medical_specialty, 030106 microbiology, Integrase inhibitor, Viremia, Gastroenterology, Major Articles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interquartile range, Internal medicine, medicine, Hiv infected patients, Protease inhibitor (pharmacology), 030212 general & internal medicine, business.industry, integrase inhibitor, HIV, medicine.disease, Reverse transcriptase, 3. Good health, residual viremia, Infectious Diseases, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load, CD8
Abstract: Background During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear. Methods HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA >200 copies/mL at ART initiation and achieved a VL 200 copies/mL or 2 VL > 50 copies/mL) while accounting for frequency of VL measurements. Results Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3–4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P < .001), female gender (P = .04), lower baseline VL (P < .001), baseline CD4+ >500 vs Conclusions VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.
Published: 2019
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48. Epstein-Barr virus biomarkers have no prognostic value in HIV-related Hodgkin lymphoma in the modern cART era

Author: Lupo, Julien, Germi, Raphaële, Lancar, Rémi, Algarte-Genin, Michèle, Hendel-Chavez, Houria, Taoufik, Yassine, Mounier, Nicolas, Partisani, Marialuisa, Bonnet, Fabrice, Meyohas, Caroline, Marchou, Bruno, Semenova, Touyana, Prevot, Sophie, Costagliola, Dominique, Morand, Patrice, Besson, Caroline, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), 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), Hôpital Archet 2 [Nice] (CHU), Le Trait d'Union, centre de soins de l'infection par le VIH [CHU Strasbourg], CHU Strasbourg, CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'Anatomie et de Cytologie Pathologiques [Béclère], Hôpital Antoine-Béclère-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Antoine-Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], hemic and lymphatic diseases
Abstract: International audience; Objectives: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era.Design: We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015.Methods: Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy.Results: Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(+) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(-) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230-3760) and 73 (0-320) copies/ml to 690 (0-1830) and 0 (0-0) copies/ml, respectively (P = 0.02 and P < 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004).Conclusion: Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era.
Published: 2019
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49. 'Real life' use of raltegravir during pregnancy in France: The Coferal-IMEA048 cohort study

Author: Claudine Duvivier, Jade Ghosn, Dominique Trias, Laurence Morand-Joubert, Odile Launay, Pierre Frange, Babacar Sylla, Amélie Menard, Ana Canestri, Marina Karmochkine, Marie-Aude Khuong, Cédric Arvieux, Lionel Piroth, Pierre Gantner, Gilles Peytavin, Karine Lacombe, Roland Landman, Laboratoire de Virologie [Strasbourg], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre d'infectiologie Necker-Pasteur [CHU Necker], Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pontchaillou [Rennes], Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses et Tropicales [CHU Tenon], CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), 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), 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), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Tenon [AP-HP], MSD France, 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), The study was funded by a grant from Merck Sharp Dohme France., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Service des maladies infectieuses et tropicales [CHU Tenon], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, animal structures, Science, Human immunodeficiency virus (HIV), medicine.disease_cause, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Obstetrics and gynaecology, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Raltegravir Potassium, Humans, Medicine, 030212 general & internal medicine, Adverse effect, Multidisciplinary, business.industry, Obstetrics, Pregnancy Outcome, medicine.disease, Raltegravir, 030112 virology, 3. Good health, Treatment Outcome, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, RNA, Viral, Gestation, Female, France, business, Research Article, Cohort study, medicine.drug
Abstract: IntroductionLimited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting.MethodsHIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns.ResultsWe included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6.ConclusionsRAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns.
Published: 2019
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50. Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals

Author: Pierre-Marie Girard, Antoine Moulignier, Ophélia Godin, Christine Katlama, Laurence Salomon, Edouard Januel, François-Xavier Lescure, Dominique Costagliola, Julien Savatovsky, Nadia Valin, Gilles Pialoux, Roland Tubiana, Yazdan Yazdanpanah, Ana Canestri, Jean-Claude Sadik, Lambert Assoumou, Pascal Roux, Cédric Lamirel, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], 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), 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), Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), 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), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service des maladies infectieuses et tropicales [CHU 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service des Maladies Infectieuses et Tropicales [CHU Tenon], and CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], CD4-CD8 Ratio, Integrase inhibitor, Cumulative Exposure, HIV Infections, Disease, 030312 virology, 03 medical and health sciences, Pharmacotherapy, Leukoencephalopathies, Internal medicine, medicine, Dementia, Humans, Pharmacology (medical), Aged, 0303 health sciences, business.industry, Case-control study, Middle Aged, Viral Load, medicine.disease, 3. Good health, Infectious Diseases, Anti-Retroviral Agents, Case-Control Studies, Cerebral Small Vessel Diseases, Etiology, Regression Analysis, Drug Therapy, Combination, Female, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD.Methods: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group.Results: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.Conclusion: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.
Published: 2019
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