16 results on '"Røge, Birgit T."'
Search Results
2. Four Weeks Treatment with Glecaprevir/Pibrentasvir + Ribavirin—A Randomized Controlled Clinical Trial
- Author
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Madsen, Lone W., primary, Christensen, Peer B., additional, Hansen, Janne F., additional, Røge, Birgit T., additional, Holm, Dorte K., additional, Dröse, Sandra, additional, and Øvrehus, Anne, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome
- Author
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Fahnøe, Ulrik, Pedersen, Martin S., Sølund, Christina, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Thielsen, Peter, Madsen, Lone G., Pedersen, Anders G., Schønning, Kristian, Weis, Nina, Bukh, Jens, Fahnøe, Ulrik, Pedersen, Martin S., Sølund, Christina, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Thielsen, Peter, Madsen, Lone G., Pedersen, Anders G., Schønning, Kristian, Weis, Nina, and Bukh, Jens
- Abstract
Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p =.0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
- Published
- 2021
4. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non‐target sites, for DAA‐based treatment and retreatment outcome
- Author
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Fahnøe, Ulrik, primary, Pedersen, Martin S., additional, Sølund, Christina, additional, Ernst, Anja, additional, Krarup, Henrik B., additional, Røge, Birgit T., additional, Christensen, Peer B., additional, Laursen, Alex L., additional, Gerstoft, Jan, additional, Thielsen, Peter, additional, Madsen, Lone G., additional, Pedersen, Anders G., additional, Schønning, Kristian, additional, Weis, Nina, additional, and Bukh, Jens, additional
- Published
- 2020
- Full Text
- View/download PDF
5. Skeletal muscle mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy and elevated p-lactate levels
- Author
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Røge, Birgit T., Calbet, José A. L., Møller, Kirsten, Ullum, Henrik, Hendel, Helle W., Gerstoft, Jan, and Pedersen, Bente K.
- Published
- 2002
6. Direct acting antiviral treatment of chronic hepatitis C in Denmark:factors associated with and barriers to treatment initiation
- Author
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Sølund, Christina, Hallager, Sofie, Pedersen, Martin S, Fahnøe, Ulrik, Ernst, Anja, Krarup, Henrik B, Røge, Birgit T, Christensen, Peer B, Laursen, Alex L, Gerstoft, Jan, Bélard, Erika, Madsen, Lone G, Schønning, Kristian, Pedersen, Anders G, Bukh, Jens, Weis, Nina, Krarup, Henrik, Hansen, Jesper Bach, and Mygind, Lone
- Subjects
hepatitis C virus ,Liver Cirrhosis ,Male ,Sustained Virologic Response ,Denmark ,Hepacivirus ,Liver Cirrhosis/epidemiology ,medicine.disease_cause ,Cohort Studies ,Liver disease ,0302 clinical medicine ,Fibrosis ,Risk Factors ,030212 general & internal medicine ,Treatment Failure ,Antiviral Agents/therapeutic use ,biology ,Gastroenterology ,Middle Aged ,factors associated with treatment ,Hepatitis C, Chronic/complications ,HCV ,Practice Guidelines as Topic ,030211 gastroenterology & hepatology ,Female ,liver disease ,Liver cancer ,Direct acting ,treatment initiation ,Cohort study ,Adult ,medicine.medical_specialty ,Hepatitis C virus ,Hepacivirus/genetics ,Antiviral Agents ,Drug Administration Schedule ,liver cancer ,03 medical and health sciences ,Chronic hepatitis ,Direct Acting Antivirals ,Internal medicine ,medicine ,Humans ,DAA ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,biology.organism_classification ,Denmark/epidemiology ,barriers to treatment ,Logistic Models ,Patient Compliance ,business - Abstract
OBJECTIVES: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark.MATERIALS AND METHODS: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause.RESULTS: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91).CONCLUSIONS: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.
- Published
- 2018
7. Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark:a nationwide cohort study
- Author
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Hallager, Sofie, Ladelund, Steen, Kjaer, Mette S, Madsen, Lone G, Belard, Erika, Laursen, Alex Lund, Gerstoft, Jan, Røge, Birgit T, Grønbaek, Karin E, Krarup, Henrik B, Christensen, Peer B, Weis, Nina, Hallager, Sofie, Ladelund, Steen, Kjaer, Mette S, Madsen, Lone G, Belard, Erika, Laursen, Alex Lund, Gerstoft, Jan, Røge, Birgit T, Grønbaek, Karin E, Krarup, Henrik B, Christensen, Peer B, and Weis, Nina
- Abstract
Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC) and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C and data from national health registries and patient charts were obtained. Tumor stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stage 0 - 3. We included 1,075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4,988 person years (PY) 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4 - 1.5] in 2002-2003 to 2.9/100 PY [2.4 - 3.4] in 2012-2013. One-year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL(-1) was 17%. Twenty-three (21%) patients were diagnosed with early stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal and most patients were diagnosed with advanced HCC with a poor prognosis. This article is protected by copyright. All rights reserved.
- Published
- 2018
8. Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals:A clinical randomized study
- Author
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Sølund, Christina, Andersen, Ellen S., Mössner, Belinda, Laursen, Alex L., Røge, Birgit T., Kjær, Mette S., Gerstoft, Jan, Christensen, Peer B., Pedersen, Martin S., Schønning, Kristian, Fahnøe, Ulrik, Bukh, Jens, Weis, Nina, Sølund, Christina, Andersen, Ellen S., Mössner, Belinda, Laursen, Alex L., Røge, Birgit T., Kjær, Mette S., Gerstoft, Jan, Christensen, Peer B., Pedersen, Martin S., Schønning, Kristian, Fahnøe, Ulrik, Bukh, Jens, and Weis, Nina
- Abstract
Objective New potent direct-acting antiviral (DAA) regimens against hepatitis C virus have been approved in recent years. However, information about the rate of adverse events (AEs) across different DAA regimens is limited. We aimed to evaluate differences in AEs and treatment efficacy in patients with chronic hepatitis C (CHC), genotype (GT) 1 or 3, randomized to two different treatment arms, correspondingly. Patients and methods We randomly assigned 96 patients in a 1: 1 ratio, to treatment for 12 weeks with either paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin (RBV) or ledipasvir/sofosbuvir (SOF)/RBV if infected with GT1 (72 patients) or to daclatasvir/SOF/RBV for 12 weeks or SOF/RBV for 24 weeks, if infected with GT3 (24 patients). Data on AEs were collected throughout the entire study period. Results A total of 70 (97%) patients with CHC with GT1 and 20 (83%) patients with GT3 achieved cure. The GT3 treatment arm was prematurely terminated, owing to change in national treatment guidelines. Thus, only AEs for GT1 patients are described. AEs occurred in 70 (97%) GT1 patients, and most common AEs were anemia (n=56/78%), fatigue (n=53/74%), and headache (n=33/46%). No difference was observed in relation to treatment group (P=1.0), anemia (P=1.0), or liver cirrhosis (P=0.53). In seven (11%) patients, AEs assessed by the investigator to be possibly related to the DAA regimen were still present 12 weeks after treatment. Conclusions We found no difference in AEs possibly related to the DAA regimen in patients with CHC, but surprisingly, AEs possibly related to the DAA regimen persisted in a significant number of patients after treatment. This finding can be of importance for clinicians in relation to patient information concerning AEs possibly related to DAA treatment.
- Published
- 2018
9. Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation.
- Author
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Sølund, Christina, Hallager, Sofie, Pedersen, Martin S., Fahnøe, Ulrik, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Bélard, Erika, Madsen, Lone G., Schønning, Kristian, Pedersen, Anders G., Bukh, Jens, Weis, Nina, and The Danhep Group
- Subjects
CHRONIC hepatitis C ,FIBROSIS ,HEPATITIS B ,ODDS ratio ,HEPATOLOGY - Abstract
Objectives: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark. Materials and Methods: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause. Results: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91). Conclusions: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
10. Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark:identification of viral resistance mutations
- Author
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Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T, Lunding, Suzanne, Barfod, Toke S, Madsen, Lone G, Tarp, Britta, Christensen, Peer B, Gerstoft, Jan, Laursen, Alex L, Bukh, Jens, Weis, Nina, Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T, Lunding, Suzanne, Barfod, Toke S, Madsen, Lone G, Tarp, Britta, Christensen, Peer B, Gerstoft, Jan, Laursen, Alex L, Bukh, Jens, and Weis, Nina
- Abstract
BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting.METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy.RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively.CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.
- Published
- 2014
11. Virological and immunological profiles among patients with undetectable viral load followed prospectively for 24 months
- Author
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Katzenstein, T L, Ullum, H, Røge, Birgit T, Wandall, J, Dickmeiss, E, Barrington, T, Skinhøj, P, Gerstoft, J, Katzenstein, T L, Ullum, H, Røge, Birgit T, Wandall, J, Dickmeiss, E, Barrington, T, Skinhøj, P, and Gerstoft, J
- Abstract
OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of = 200 HIV-RNA copies/mL.METHODS: A prospective study of one hundred and three patients was undertaken with an inclusion criteria of plasma viral load of = 200 copies/mL. The patients had advanced HIV infection; 25% had developed AIDS. Patients were seen every 6 months for a period of 2 years.RESULTS: The median plasma viral load was < 20 copies/mL with no increase during follow-up. Thirty-one per cent had plasma viral load of = 20 copies/mL at all visits, 44% had >/= 1 measurement with 21-200 and 25% had >/= 1 sample with plasma HIV-RNA > 200 copies/mL. Lymphoid tissue viral load was low at enrolment and declined further during follow-up. Baseline HIV-DNA and immunoglobulin (IgA) differed significantly between the plasma viral load rebound groups (P < 0.05).CONCLUSION: In this cohort, selected solely on the basis of having a plasma viral load of = 200 copies/mL, we found stable or declining viral loads in the measured compartments during 2 years of follow-up. Baseline HIV-DNA and IgA levels were higher among patients with less complete virological suppression relative to patients with persistently undetectable plasma HIV-RNA. Hence, a high cellular level of HIV-DNA and high plasma IgA may predict subsequent development of low-grade viraemia.
- Published
- 2003
12. Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: A nationwide population-based cohort study
- Author
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Larsen, Mette Vang, primary, Omland, Lars Haukali, additional, Gerstoft, Jan, additional, Røge, Birgit T., additional, Larsen, Carsten Schade, additional, Pedersen, Gitte, additional, Obel, Niels, additional, and Kronborg, Gitte, additional
- Published
- 2010
- Full Text
- View/download PDF
13. Nationwide Experience of Treatment with Protease Inhibitors in Chronic Hepatitis C Patients in Denmark: Identification of Viral Resistance Mutations.
- Author
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Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T., Lunding, Suzanne, Barfod, Toke S., Madsen, Lone G., Tarp, Britta, Christensen, Peer B., Gerstoft, Jan, Laursen, Alex L., Bukh, Jens, Weis, Nina, and null, null
- Subjects
CHRONIC hepatitis C ,GENETIC mutation ,PROTEASE inhibitors ,RIBAVIRIN ,POLYMERASE chain reaction ,PATIENTS - Abstract
Background and Aims: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. Methods: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. Results: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. Conclusions: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
14. K65R with and without S68: A New Resistance Profile in Vivo Detected in Most Patients Failing Abacavir, Didanosine and Stavudine
- Author
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Røge, Birgit T, primary, Katzenstein, Terese L, additional, Obel, Niels, additional, Nielsen, Henrik, additional, Kirk, Ole, additional, Pedersen, Court, additional, Mathiesen, Lars, additional, Lundgren, Jens, additional, and Gerstoft, Jan, additional
- Published
- 2003
- Full Text
- View/download PDF
15. Comparison of P-Triglyceride Levels among Patients with Human Immunodeficiency Virus on Randomized Treatment with Ritonavir, Indinavir or Ritonavir/Saquinavir.
- Author
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Røge, Birgit T., Katzenstein, Terese L., and Gerstoft, Jan
- Subjects
- *
TRIGLYCERIDES , *HIV infections , *THERAPEUTICS , *PROTEASE inhibitors , *REVERSE transcriptase , *CHEMICAL inhibitors - Abstract
This study compared the alterations in p-triglyceride (PT) in 111 protease inhibitor (PI)-naive patients on randomized treatment with either indinavir (800 mg 3 times daily), ritonavir (600 mg twice daily) or ritonavir/saquinavir (400 mg each twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs). PT (non-fasting) was measured at regular intervals until week 48. PT levels were evaluated in relation to PI regime, CD4 cell count and prior NRTI experience. The effect on PT levels of changing PI regime was analysed. For 24 patients fasting and non-fasting PT values were correlated. In the ritonavir-containing arms PT levels increased significantly (median PT at baseline: 1.80 mmol/l; week 36: 2.3 mmol/l; p < 0.001). In the indinavir arm no significant rise in PT levels was observed. Comparing the PI arms at week 48 showed significantly higher levels of PT in the ritonavir-containing arms than in the indinavir arm (p < 0.001). There was a high correlation between fasting and non-fasting PT values (p < 0.001, ρ = 0.88). A significant decline in PT values when changing PI treatment was observed (n =13, p =0.016). Ritonavir-containing regimens caused a rapid and sustained elevation of PT values, while indinavir did not significantly affect PT levels. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
16. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome.
- Author
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Fahnøe U, Pedersen MS, Sølund C, Ernst A, Krarup HB, Røge BT, Christensen PB, Laursen AL, Gerstoft J, Thielsen P, Madsen LG, Pedersen AG, Schønning K, Weis N, and Bukh J
- Subjects
- Drug Resistance, Viral genetics, Drug Therapy, Combination, Genotype, Hepacivirus genetics, Humans, Retreatment, Treatment Failure, Viral Nonstructural Proteins genetics, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy
- Abstract
Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
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