摘要
AIMTo describe factors associated with treatment failure and frequency of resistance-associated substitutions (RAS).METHODSHuman immunodefciency 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 defned as: (1) non-response [HCV-RNA remained detectable during treatment, at end of treatment (EOT)]; and (2) relapse (HCV-RNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specifc RAS. Factors associated with failure were determined using logistic regression models.RESULTSAmong 559 patients, 77% had suppressed plasmaHIV-RNA 〈 50 copies/mL at DAA treatment initiation41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in22 patients and were mainly relapses (17, 77%) thenundefined failures (3, 14%) and non-responses (29%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5A or NS5B RAS were detected in10/14 patients with samples available for sequencinganalysis. After adjustment for age, sex, ribavirin useHCV genotype and treatment duration, low platelecount was the only factor signifcantly associated with ahigher risk of failure (OR: 6.5; 95%CI: 1.8-22.6). CONCLUSIONOnly 3.9% HIV-HCV coinfected patients failed DAAregimens and RAS were found in 70% of those failingLow platelet count was independently associated withvirological failure.
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.
作者
Dominique Salmon
Pascale Trimoulet
Camille Gilbert
Caroline Solas
Eva Lafourcade
Julie Chas
Lionel Piroth
Karine Lacombe
Christine Katlama
Gilles Peytavin
Hugues Aumaitre
Laurent Alric
Franoois Boué
Philippe Morlat
Isabelle Poizot-Martin
Eric Billaud
Eric Rosenthal
Alissa Naqvi
Patrick Miailhes
Firouzé Bani-Sadr
Laure Esterle
Patrizia Carrieri
Franoois Dabis
Philippe Sogni
Linda Wittkop
无
Dominique Salmon;Pascale Trimoulet;Camille Gilbert;Caroline Solas;Eva Lafourcade;Julie Chas;Lionel Piroth;Karine Lacombe;Christine Katlama;Gilles Peytavin;Hugues Aumaitre;Laurent Alric;Franoois Boué;Philippe Morlat;Isabelle Poizot-Martin;Eric Billaud;Eric Rosenthal;Alissa Naqvi;Patrick Miailhes;Firouzé Bani-Sadr;Laure Esterle;Patrizia Carrieri;Franoois Dabis;Philippe Sogni;Linda Wittkop;无(Assistance Publique des Hopitaux de Paris,Hopitaux Universitaires Paris Centre,Hopital Hotel Dieu,Unitédes Maladies infectieuses et tropicales,Paris 75004,France;Université Paris Descartes,Sorbonne Paris Cité,Paris 75006,France;Trimoulet,CHU de Bordeaux,Hopital Pellegrin,Laboratoire de Virologie,Bordeaux 33000,France;Trimoulet,CNRS-UMR 5234,Microbiologie fondamentale et Pathogénicité,Universitéde Bordeaux,Bordeaux 3000,France;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;APHM,Hopital La Timone,Laboratoire de Pharmacocinétique et Toxicologie,Marseille 13005,France;Centre Hospitalier Universitaire de Dijon,Département d'Infectiologie,Dijon cedex 21079,France;INSERM-CIC 1342 Universitéde Bourgogne,Dijon 21000,France;Assistance Publique des Hopitaux de Paris,GHUEP site Saint-Antoine,Services Maladies infectieuses et tropicales,Paris 75011,France;UniversitéPierre et Marie Curie,UMR S1136,Institut Pierre Louis d' Epidémiologie et de SantéPublique,Paris 75646,France;UniversitéParis-Sorbonne,Paris 75005,France;Assistance Publique des Hopitaux de Paris Hopital PitiéSalpêtrière,Services Maladies infectieuses et tropicales,Paris 75013,France;Assistance Publique des Hopitaux de Paris,Hopital Bichat-Claude Bernard,Laboratoire de Pharmacologie,Paris 75877,France;IAME,UMR 1137,Sorbonne Paris Cité,INSERM,UniversitéParis Diderot,Paris 75890,France;Centre Hospitalier de Perpignan,Service Maladies infectieuses et tropicales,Perpignan 66000,Franc;Centre Hospitalier Universitaire de Toulouse,Hopital Purpan,Service Médecine interne-Pole Digestif,Toulouse 31300,France;UMR 152 IRD UniversitéToulouseⅢ,Paul Sabatier,Toulouse 31330,France;Hopital Antoine-Béclère,Assistance Publique des Hopitaux de Paris,UniversitéParis Sud,Service Médecine interne et immunologie,Clamart 92140,France;Centre Hospitalier Universitaire de Bordeaux,Service de médecine interne,Hopital Saint-André,Bordeaux 33000,France;Univ,APHM Sainte-Marguerite,Service d'Immuno-hématologie clinique,Marseille 13274,France;Sciences Economiques and Sociales de la Santéand Traitement de l'Information Médicale,UMR912 INSERM,Aix-Marseille Université,IRD,Marseille 13009,France;Department of Infectious Diseases,CHU de Nantes and CIC 1413,Inserm,Nantes 44000,France;Centre Hospitalier Universitaire de Nice,Service de Médecine Interne,Hopital l'Archet,Nice 06202,France;Centre Hospitalier Universitaire de Nice,Service de Médecine Interne,Hopital l'Archet,Nice 06202,France;Universitéde Nice-Sophia Antipolis,Nice 06100,France;Centre Hospitalier Universitaire de Nice,Service d'Infectiologie,Hopital l'Archet,Nice 06100,France;Service des Maladies Infectieuses et Tropicales,Hospices Civils de Lyon,Hopital de la Croix Rousse,Lyon 69004,France;Centre Hospitalier Universitaire de Reims,Service de Médecine Interne,Maladies Infectieuses et Immunologie Clinique,Reims 51100,France;Facultéde Médecine EA-4684/SFR CAP-SANTE,Universitéde Reims,Champagne-Ardenne,Reims 51100,France;Assistance Publique des Hopitaux de Paris,Hopital Cochin,Service d' Hépatologie,Paris 75014,France;Inserm U-1223-Institut Pasteur,Paris 75015,France;Assistance Publique des Hôpitaux de Paris,Hôpital Tenon,Service Maladies infectieuses et tropicales,Paris 75020,France;CHU de Bordeaux,Pôle de santé Publique,Service d’information médicale,Bordeaux F-33000,France;ANRS CO13 Hepavih study group)
基金
Supported by Inserm-ANRS(French National Institute for Health and Medical Research-ANRS/France REcherche Nord and Sud Sida-hiv Hépatites)