Wang, Dao Sen

Phu, Amy

McKee, Kristen

Strasser, Simone I

Sheils, Sinead

Weltman, Martin

Sellar, Sue

Davis, Joshua S

Young, Mel

Braund, Alicia

Farrell, Geoffrey C

Blunn, Anne

Harding, Damian

Ralton, Lucy

Muller, Kate

Davison, Scott A

Shaw, David

Wood, Marnie

Hajkowicz, Krispin

Skolen, Richard

Davies, Jane

Tate-Baker, Jaclyn

Doyle, Adam

Tuma, Rhoda

Hazeldine, Simon

Lam, Wendy

Edmiston, Natalie

Zohrab, Krista

Pratt, William

Watson, Belinda

Zekry, Amany

Stephens, Carlie

Clark, Paul J

Day, Melany

Park, Gordon

Kim, Hami

Wilson, Mark

McGarity, Bruce

Menzies, Natalie

Russell, Darren

Lam, Thao

Boyd, Peter

Kok, Jen

George, Jacob

Douglas, Mark W

2024-03-31

Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported.We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome.Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir.In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

AW Morrow Gastroenterology and Liver Centre, The University of Sydney and Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

AW Morrow Gastroenterology and Liver Centre, The University of Sydney and Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Department of Gastroenterology and Hepatology, Nepean Hospital, Kingswood, NSW, Australia.

Department of Gastroenterology and Hepatology, Nepean Hospital, Kingswood, NSW, Australia.

Department of Infectious Diseases, University of Newcastle and John Hunter Hospital, Newcastle, NSW, Australia.

Department of Infectious Diseases, University of Newcastle and John Hunter Hospital, Newcastle, NSW, Australia.

Department of Gastroenterology and Hepatology, Gold Coast University Hospital, Southport, QLD, Australia.

Department of Gastroenterology and Hepatology, Australian National University and The Canberra Hospital, Canberra, ACT, Australia.

Department of Gastroenterology and Hepatology, Australian National University and The Canberra Hospital, Canberra, ACT, Australia.

Department of Gastroenterology and Hepatology, Lyell McEwin Hospital, Elizabeth Vale, SA, Australia.

Department of Gastroenterology and Hepatology, Lyell McEwin Hospital, Elizabeth Vale, SA, Australia.

Department of Gastroenterology and Hepatology, Flinders Medical Centreand Flinders University, Adelaide, SA, Australia.

Department of Gastroenterology and Hepatology, University of New South Wales and Liverpool Hospital, Liverpool, NSW, Australia.

Department of Infectious Diseases, Royal Adelaide Hospital, Adelaide, SA, Australia.

Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Menzies School of Health Research and Royal Darwin Hospital, Darwin, NT, Australia.

Menzies School of Health Research and Royal Darwin Hospital, Darwin, NT, Australia.

Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, WA, Australia.

Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, WA, Australia.

Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.

Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.

Department of Gastroenterology and Hepatology, School of Medicine, Western Sydney University, Sydney, NSW, Australia.

Department of Gastroenterology and Hepatology, School of Medicine, Western Sydney University, Sydney, NSW, Australia.

Department of Medicine, Shoalhaven Hospital, Nowra, NSW, Australia.

Department of Medicine, Shoalhaven Hospital, Nowra, NSW, Australia.

Department of Gastroenterology and Hepatology, St George Hospital, Kogarah, NSW, Australia.

Department of Gastroenterology and Hepatology, St George Hospital, Kogarah, NSW, Australia.

Rockhampton Blood Borne Virus & Sexual Health Service and School of Medicine, University of Brisbane, Brisbane, QLD, Australia.

Rockhampton Blood Borne Virus & Sexual Health Service and School of Medicine, University of Brisbane, Brisbane, QLD, Australia.

Department of Gastroenterology and Hepatology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Department of Gastroenterology and Hepatology, Royal North Shore Hospital, St Leonards, NSW, Australia.

Department of Gastroenterology and Hepatology, Royal Hobart Hospital, Hobart, TAS, Australia.

Bathurst Liver Clinic, Bathurst, NSW, Australia.

Bathurst Liver Clinic, Bathurst, NSW, Australia.

Cairns Sexual Health Service and James Cook University Cairns, St Cairns City, QLD, Australia.

Department of Drug Health, Western Sydney Local Health District, Westmead, NSW, Australia.

Department of Medicine, Cairns Hospital, Cairns, QLD, Australia.

Centre for Infectious Diseases and Microbiology Laboratory Services, NSW Health Pathology-Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW, Australia.

Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Sydney, NSW, Australia.

Open Forum Infect Dis . 2024 Mar 18;11(4):ofae155. doi: 10.1093/ofid/ofae155. eCollection 2024 Apr.

2328-8957

0000-0003-4621-3485

https://pubmed.ncbi.nlm.nih.gov/38651137/?otool=iaurydwlib

https://hdl.handle.net/10137/13275

Hepatitis C

antimicrobial resistance

antiviral therapy

direct acting antivirals

drug resistance

Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Journal Article

Publication