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Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

查看全文 作　　者：Dominique [1,2]Salmon;Pascale [3,4]Trimoulet;Camille [5]Gilbert;Caroline [6]Solas;Eva [5]Lafourcade;Julie [32]Chas;Lionel [7,8]Piroth;Karine [8,9]Lacombe;Christine [10,11]Katlama;Gilles [12,13,14]Peytavin;Hugues [15]Aumaitre;Laurent [16,17]Alric;Franoois [18]Boué;Philippe [5,19]Morlat;Isabelle Poizot-[20,21]Martin;Eric [22]Billaud;Eric [23,24,25]Rosenthal;Alissa [26]Naqvi;Patrick [27]Miailhes;Firouzé Bani-[28,29]Sadr;Laure [1]Esterle;Patrizia [21]Carrieri;Franoois [1]Dabis;Philippe [30,31]Sogni;Linda [5,33]Wittkop;[34]无 高影响力作者 机构地区：[1]Assistance Publique des Hopitaux de Paris,Hopitaux Universitaires Paris Centre,Hopital Hotel Dieu,Unitédes Maladies infectieuses et tropicales,Paris 75004,France;[2]Université Paris Descartes,Sorbonne Paris Cité,Paris 75006,France;[3]Trimoulet,CHU de Bordeaux,Hopital Pellegrin,Laboratoire de Virologie,Bordeaux 33000,France;[4]Trimoulet,CNRS-UMR 5234,Microbiologie fondamentale et Pathogénicité,Universitéde Bordeaux,Bordeaux 3000,France;[5]Philippe Morlat,Laure Esterle,Francois Dabis,Linda Wittkop,Univ.Bordeaux,ISPED,Inserm,Bordeaux Population Health Research Center,team MORPH3EUS,UMR 1219,CIC-EC 1401,Bordeaux F-33000,France;[6]APHM,Hopital La Timone,Laboratoire de Pharmacocinétique et Toxicologie,Marseille 13005,France;[7]Centre Hospitalier Universitaire de Dijon,Département d'Infectiologie,Dijon cedex 21079,France;[8]INSERM-CIC 1342 Universitéde Bourgogne,Dijon 21000,France;[9]Assistance Publique des Hopitaux de Paris,GHUEP site Saint-Antoine,Services Maladies infectieuses et tropicales,Paris 75011,France;[10]UniversitéPierre et Marie Curie,UMR S1136,Institut Pierre Louis d' Epidémiologie et de SantéPublique,Paris 75646,France;[11]UniversitéParis-Sorbonne,Paris 75005,France;[12]Assistance Publique des Hopitaux de Paris Hopital PitiéSalpêtrière,Services Maladies infectieuses et tropicales,Paris 75013,France;[13]Assistance Publique des Hopitaux de Paris,Hopital Bichat-Claude Bernard,Laboratoire de Pharmacologie,Paris 75877,France;[14]IAME,UMR 1137,Sorbonne Paris Cité,INSERM,UniversitéParis Diderot,Paris 75890,France;[15]Centre Hospitalier de Perpignan,Service Maladies infectieuses et tropicales,Perpignan 66000,Franc;[16]Centre Hospitalier Universitaire de Toulouse,Hopital Purpan,Service Médecine interne-Pole Digestif,Toulouse 31300,France;[17]UMR 152 IRD UniversitéToulouseⅢ,Paul Sabatier,Toulouse 31330,France;[18]Hopital Antoine-Béclère,Assistance Publique des Hopitaux de Paris,UniversitéParis Sud,Service Médecine interne et immunologie,Clamart 92140,France;[19]Centre Hospitalier Universitaire de Bordeaux,Service de médecine interne,Hopital Saint-André,Bordeaux 33000,France;[20]Univ,APHM Sainte-Marguerite,Service d'Immuno-hématologie clinique,Marseille 13274,France;[21]Sciences Economiques and Sociales de la Santéand Traitement de l'Information Médicale,UMR912 INSERM,Aix-Marseille Université,IRD,Marseille 13009,France;[22]Department of Infectious Diseases,CHU de Nantes and CIC 1413,Inserm,Nantes 44000,France;[23]Centre Hospitalier Universitaire de Nice,Service de Médecine Interne,Hopital l'Archet,Nice 06202,France;[24]Centre Hospitalier Universitaire de Nice,Service de Médecine Interne,Hopital l'Archet,Nice 06202,France;[25]Universitéde Nice-Sophia Antipolis,Nice 06100,France;[26]Centre Hospitalier Universitaire de Nice,Service d'Infectiologie,Hopital l'Archet,Nice 06100,France;[27]Service des Maladies Infectieuses et Tropicales,Hospices Civils de Lyon,Hopital de la Croix Rousse,Lyon 69004,France;[28]Centre Hospitalier Universitaire de Reims,Service de Médecine Interne,Maladies Infectieuses et Immunologie Clinique,Reims 51100,France;[29]Facultéde Médecine EA-4684/SFR CAP-SANTE,Universitéde Reims,Champagne-Ardenne,Reims 51100,France;[30]Assistance Publique des Hopitaux de Paris,Hopital Cochin,Service d' Hépatologie,Paris 75014,France;[31]Inserm U-1223-Institut Pasteur,Paris 75015,France;[32]Assistance Publique des Hôpitaux de Paris,Hôpital Tenon,Service Maladies infectieuses et tropicales,Paris 75020,France;[33]CHU de Bordeaux,Pôle de santé Publique,Service d’information médicale,Bordeaux F-33000,France;[34]ANRS CO13 Hepavih study group高影响力机构 出　　处：《World Journal of Hepatology》索引2018年第10卷第11期,共11页高影响力期刊 基　　金：Supported by Inserm-ANRS(French National Institute for Health and Medical Research-ANRS/France REcherche Nord and Sud Sida-hiv Hépatites) 摘　　要：AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure. 关 键 词：耐药性 治疗方法 患者 肝病
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