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Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care

BACKGROUND: There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV—a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient...

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Autores principales: Rossi, Carmine, Young, Jim, Martel-Laferrière, Valérie, Walmsley, Sharon, Cooper, Curtis, Wong, Alexander, Gill, M John, Klein, Marina B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411211/
https://www.ncbi.nlm.nih.gov/pubmed/30882016
http://dx.doi.org/10.1093/ofid/ofz055
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author Rossi, Carmine
Young, Jim
Martel-Laferrière, Valérie
Walmsley, Sharon
Cooper, Curtis
Wong, Alexander
Gill, M John
Klein, Marina B
author_facet Rossi, Carmine
Young, Jim
Martel-Laferrière, Valérie
Walmsley, Sharon
Cooper, Curtis
Wong, Alexander
Gill, M John
Klein, Marina B
author_sort Rossi, Carmine
collection PubMed
description BACKGROUND: There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV—a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients. METHODS: We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure. RESULTS: Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure—particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38–6.0; posterior OR, 1.0; 95% CrI, 0.40–2.5). CONCLUSIONS: DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure.
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spelling pubmed-64112112019-03-15 Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care Rossi, Carmine Young, Jim Martel-Laferrière, Valérie Walmsley, Sharon Cooper, Curtis Wong, Alexander Gill, M John Klein, Marina B Open Forum Infect Dis Major Article BACKGROUND: There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV—a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients. METHODS: We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure. RESULTS: Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure—particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38–6.0; posterior OR, 1.0; 95% CrI, 0.40–2.5). CONCLUSIONS: DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure. Oxford University Press 2019-02-13 /pmc/articles/PMC6411211/ /pubmed/30882016 http://dx.doi.org/10.1093/ofid/ofz055 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Rossi, Carmine
Young, Jim
Martel-Laferrière, Valérie
Walmsley, Sharon
Cooper, Curtis
Wong, Alexander
Gill, M John
Klein, Marina B
Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title_full Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title_fullStr Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title_full_unstemmed Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title_short Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV–Coinfected Patients in Clinical Care
title_sort direct-acting antiviral treatment failure among hepatitis c and hiv–coinfected patients in clinical care
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411211/
https://www.ncbi.nlm.nih.gov/pubmed/30882016
http://dx.doi.org/10.1093/ofid/ofz055
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