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

引用

World Journal of Hepatology 2018年第11期10卷 856-866页

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 Assistance Publique des Hopitaux de Paris Hopitaux Universitaires Paris CentreHopital Hotel DieuUnitédes Maladies infectieuses et tropicalesParis 75004France Université Paris Descartes Sorbonne Paris CitéParis 75006France Trimoulet CHU de BordeauxHopital PellegrinLaboratoire de VirologieBordeaux 33000France Trimoulet CNRS-UMR 5234Microbiologie fondamentale et PathogénicitéUniversitéde BordeauxBordeaux 3000France Philippe Morlat Laure EsterleFrancois DabisLinda WittkopUniv.BordeauxISPEDInsermBordeaux Population Health Research Centerteam MORPH3EUSUMR 1219CIC-EC 1401Bordeaux F-33000France APHM Hopital La TimoneLaboratoire de Pharmacocinétique et ToxicologieMarseille 13005France Centre Hospitalier Universitaire de Dijon Département d'InfectiologieDijon cedex 21079France INSERM-CIC 1342 Universitéde Bourgogne Dijon 21000France Assistance Publique des Hopitaux de Paris GHUEP site Saint-AntoineServices Maladies infectieuses et tropicalesParis 75011France UniversitéPierre et Marie Curie UMR S1136Institut Pierre Louis d' Epidémiologie et de SantéPubliqueParis 75646France UniversitéParis-Sorbonne Paris 75005France Assistance Publique des Hopitaux de Paris Hopital PitiéSalpêtrière Services Maladies infectieuses et tropicalesParis 75013France Assistance Publique des Hopitaux de Paris Hopital Bichat-Claude BernardLaboratoire de PharmacologieParis 75877France IAME UMR 1137Sorbonne Paris CitéINSERMUniversitéParis DiderotParis 75890France Centre Hospitalier de Perpignan Service Maladies infectieuses et tropicalesPerpignan 66000Franc Centre Hospitalier Universitaire de Toulouse Hopital PurpanService Médecine interne-Pole DigestifToulouse 31300France UMR 152 IRD UniversitéToulouseⅢ Paul SabatierToulouse 31330France Hopital Antoine-Béclère Assistance Publique des Hopitaux de ParisUniversitéParis SudService Médecine interne et immunologieClamart 92140France Centre Hospitalier Universitaire de Bordeaux Service de médecine interneHopital Saint-AndréBordeaux 33000France Uni

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 *** 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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