Retreatment with elbasvir, grazoprevir, sofosbuvir ± ribavirin is effective for GT3 and GT1/4/6 HCV infection after relapse.


Journal

Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857

Informations de publication

Date de publication:
12 2019
Historique:
received: 03 04 2019
revised: 31 05 2019
accepted: 04 07 2019
pubmed: 30 7 2019
medline: 6 10 2020
entrez: 30 7 2019
Statut: ppublish

Résumé

Despite highly effective direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection, some patients experience virological relapse. Salvage regimens should include multiple agents to suppress emergence of resistance-associated substitutions (RAS) and minimise treatment failure. The combination of sofosbuvir (SOF) and elbasvir/grazoprevir (ELB/GZR) ±ribavirin (RBV) is an effective retreatment strategy for HCV genotype (GT)1 and 4 infection. We hypothesised that SOF and ELB/GZR (±RBV) would also be an effective salvage regimen for DAA-experienced GT3 patients. We evaluated the efficacy and safety of SOF/ELB/GZR ± RBV in DAA-experienced participants with chronic HCV infection who had prior relapse. Participants were treated at four hospitals between December 2016 and March 2018 for either 12- or 16-weeks. The primary endpoint was sustained virological response at week 12 post-treatment (SVR12) using intention-to-treat analysis. There were 40 participants included in the analysis. The mean age was 53 years, 53% had GT3, 33% had GT1 infection and 63% had cirrhosis. Fifty-eight percent were treated for 12 weeks, 42% were treated for 16 weeks and 90% received RBV. The SVR12 rate was 98% overall, 100% in non-GT3 participants and 95% in GT3 participants. One GT3 cirrhotic participant relapsed. ELB/GZR was stopped at week 6 in one GT3 cirrhotic participant who switched to SOF/velpatasvir/RBV for a further 12 weeks and achieved SVR12. RBV dose reduction was required in two participants. Treatment was otherwise well tolerated. The combination of SOF/ELB/GZR ± RBV is effective and safe for difficult-to-cure patients who relapse after first-line DAA, including those with cirrhosis and GT3 infection.

Identifiants

pubmed: 31355968
doi: 10.1111/liv.14201
doi:

Substances chimiques

Amides 0
Antiviral Agents 0
Benzofurans 0
Carbamates 0
Cyclopropanes 0
Imidazoles 0
Quinoxalines 0
Sulfonamides 0
Ribavirin 49717AWG6K
grazoprevir 4O2AB118LA
elbasvir 632L571YDK
Sofosbuvir WJ6CA3ZU8B

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2285-2290

Informations de copyright

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Références

Pawlotsky J-M. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016;151(1):70-86.
Wyles D, Mangia A, Cheng W, et al. Long-term persistence of HCV NS5A resistance associated substitutions after treatment with the HCV NS5A inhibitor, ledipasvir, without sofosbuvir. Antivir Ther. 2017;23:229-238.
Therapeutic goods administration. Product Information, Zepatier. https://www.tga.gov.au/sites/default/files/auspar-grazoprevir-170515-pi.pdf. Accessed September 15, 2018.
de Lédinghen V, Laforest C, Hézode C, et al. Retreatment with sofosbuvir plus grazoprevir/elbasvir plus ribavirin of patients with hepatitis C virus genotype 1 or 4 who previously failed an NS5A- or NS3-containing regimen: the ANRS HC34 REVENGE study. Clin Infect Dis. 2017;66(7):1013-1018.
Gane E, Nahass R, Luketic V, et al. Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naïve, noncirrhotic HCV genotype 3-infected patients. J Viral Hepat. 2017;24(10):895-899.
Foster GR, Agarwal K, Cramp ME, et al. Elbasvir/grazoprevir and sofosbuvir for hepatitis C virus genotype 3 infection with compensated cirrhosis: a randomized trial. Hepatology. 2018;67(6):2113-2126.
Pharmaceutical Benefit Scheme; Australian Government. 'General Statement for Drugs for the Treatment of Hepatitis C'. http://www.pbs.gov.au/healthpro/explanatory-notes/general-statement-pdf/general-statement-hepatitis-cpdf. Accessed December 6, 2018.
Werner CR, Schwarz JM, Egetemeyr DP, et al. Second-generation direct-acting-antiviral hepatitis C virus treatment: efficacy, safety, and predictors of SVR12. World J Gastroenterol. 2016;22(35):8050.
Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134-2146.
Bourlière M, Gordon SC, Ramji A, et al. Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks as a salvage regimen in NS5A inhibitor-experienced patients with genotype 1-6 infection: the phase 3 POLARIS-1 study. Hepatology. 2016;64(Suppl. 1):102A-A3.
Gane EJ, Shiffman ML, Etzkorn K, et al. Sofosbuvir-velpatasvir with ribavirin for 24 weeks in hepatitis C virus patients previously treated with a direct-acting antiviral regimen. Hepatology. 2017;66(4):1083-1089.
Lawitz EJ, Dvory-Sobol H, Doehle BP, et al. Clinical resistance to velpatasvir (GS-5816), a novel pan-genotypic inhibitor of the hepatitis C virus NS5A protein. Antimicrob Agents Chemother. 2016;60(9):5368-5378.
Pawlotsky J-M, Negro F, Aghemo A, et al. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69(2):461-511.
Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727-733.
Waziry R, Hajarizadeh B, Grebely J, et al. Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression. J Hepatol. 2017;67(6):1204-1212.

Auteurs

Timothy Papaluca (T)

St Vincent's Hospital and the University of Melbourne, Fitzroy, Vic., Australia.

Marie Sinclair (M)

The Austin Hospital, Melbourne, Vic., Australia.

Paul Gow (P)

The Austin Hospital, Melbourne, Vic., Australia.

Stephen Pianko (S)

Monash Health and Monash University, Melbourne, Vic., Australia.

William Sievert (W)

Monash Health and Monash University, Melbourne, Vic., Australia.

Niranjan Arachchi (N)

Western Health, Melbourne, Vic., Australia.

Karla Cameron (K)

Western Health, Melbourne, Vic., Australia.

Scott Bowden (S)

Victorian Infectious Disease Reference Laboratory, Melbourne, Vic., Australia.

Jacinta O'Keefe (J)

Victorian Infectious Disease Reference Laboratory, Melbourne, Vic., Australia.

Joseph Doyle (J)

Department of Infectious Diseases, The Alfred and Monash University, Melbourne, Vic., Australia.
Burnet Institute, Melbourne, Vic., Australia.

Mark Stoove (M)

Burnet Institute, Melbourne, Vic., Australia.

Margaret Hellard (M)

Burnet Institute, Melbourne, Vic., Australia.

David Iser (D)

St Vincent's Hospital and the University of Melbourne, Fitzroy, Vic., Australia.

Alexander Thompson (A)

St Vincent's Hospital and the University of Melbourne, Fitzroy, Vic., Australia.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH