scholarly journals Resistance-Associated Substitutions/Variants Correlate to Therapeutic Outcomes of Novel Direct-Acting Antivirals in Different HCV Genotype Treated Individuals

Genotyping ◽  
2018 ◽  
Author(s):  
Imran Shahid ◽  
Munjed Mahmoud Ibrahim ◽  
Muhammad Usman Nawaz ◽  
Mohammad Tarque Imam ◽  
Waleed H. AlMalki
Keyword(s):  
Direct Acting Antivirals ◽  
Hcv Genotype ◽  
Therapeutic Outcomes ◽  
Direct Acting

scholarly journals Compartmentalization of Resistance-Associated Substitutions in HIV/HCV-Infected Patients: Possible Correlation with Infecting HCV Genotype

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1486
Author(s):  
Giulia Morsica ◽  
Riccardo Vercesi ◽  
Hamid Hasson ◽  
Emanuela Messina ◽  
Caterina Uberti-Foppa ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Viral Population ◽  
Plasma Samples ◽  
Direct Acting Antivirals ◽  
Hcv Treatment ◽  
Major Site ◽  
Hcv Genotype ◽  
Naturally Occurring ◽  
Resistant Strains ◽  
Direct Acting

Resistance-associated substitutions (RASs) may exist prior to treatment and contribute to the failure of treatment with direct-acting antivirals (DAAs). As the major site of HCV replication, naturally occurring variants with RASs may segregate into the liver. In the present study, we performed viral population sequencing to retrospectively investigate the NS3 and NS5A RAS profiles in 34 HIV/HCV coinfected patients naïve to anti-HCV treatment who underwent diagnostic liver biopsy between 2000 and 2006 and had liver and plasma samples available. Sixteen were infected by HCV genotype (GT) 1a, 11 by GT3a, and 7 by GT4d. The analysis of the NS3 domain in GT1a showed a difference in strain between the liver and plasma in three cases, with a preponderance of specific RASs in the liver compartment. In GT4d samples, 6/7 coupled liver and plasma samples were concordant with no RASs. Sequence analysis of the NS5A domain showed the presence of RASs in the livers of 2/16 patients harboring GT1a but not in the corresponding plasma. In GT4d, NS5A RASs were detected in 7/7 liver tissues and 5/7 plasma samples. NS3 domain and NS5A domain were found to be conserved in plasma and livers of patients infected with GT3a. Thus, RASs within GT1a and GT4d more likely segregate into the liver and may explain the emergence of resistant strains during DAA treatment.

Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients

2016 ◽  
Vol 10 (5) ◽  
pp. 789-798 ◽  
Author(s):  
Dong Ji ◽  
Guo-Feng Chen ◽  
Cheng Wang ◽  
Yu-Dong Wang ◽  
Qing Shao ◽  
...  
Keyword(s):  
Direct Acting Antivirals ◽  
Hcv Genotype ◽  
Genotype 1B ◽  
Cirrhotic Patients ◽  
Direct Acting

scholarly journals Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection

2015 ◽  
Vol 60 (3) ◽  
pp. 1546-1555 ◽  
Author(s):  
Eric J. Lawitz ◽  
William D. O'Riordan ◽  
Armen Asatryan ◽  
Bradley L. Freilich ◽  
Terry D. Box ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Genotype 1 ◽  
Direct Acting Antivirals ◽  
Hcv Genotype ◽  
Compensated Cirrhosis ◽  
Hcv Genotype 1 ◽  
Direct Acting

ABT-493 is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor, and ABT-530 is an HCV NS5A inhibitor. These direct-acting antivirals (DAAs) demonstrated potent antiviral activity against major HCV genotypes and high barriers to resistancein vitro. In this open-label dose-ranging trial, antiviral activity and safety were assessed during 3 days of monotherapy with ABT-493 or ABT-530 in treatment-naive adults with HCV genotype 1 infection, with or without compensated cirrhosis. The presence of baseline resistance-associated variants (RAVs) was also evaluated. The mean maximal decreases in HCV RNA levels from baseline were approximately 4 log10IU/ml for all ABT-493 doses ranging from 100 mg to 700 mg and for ABT-530 doses of ≥40 mg. There were no meaningful differences in viral load declines for patients with versus without compensated cirrhosis. Twenty-four (50%) of the baseline samples from patients treated with ABT-493 had RAVs to NS3/4A protease inhibitors. Among 40 patients treated with ABT-530, 6 (15%) carried baseline RAVs to NS5A inhibitors. Viral load declines in patients with single baseline NS5A RAVs were similar to those in patients without RAVs. One patient harbored baseline RAVs at 3 NS5A positions and appeared to have a slightly less robust viral load decline on day 3 of monotherapy. No serious or grade 3 (severe) or higher adverse events and no clinically relevant laboratory abnormalities were observed with either compound. ABT-493 and ABT-530 demonstrated potent antiviral activity and acceptable safety during 3-day monotherapy in patients with HCV genotype 1 infection, with or without compensated cirrhosis. Based on these results, phase II studies assessing the combination of these DAAs for the treatment of chronic HCV infection in patients with or without compensated cirrhosis have been initiated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01995071.)

Very late relapse in an HCV genotype 3-infected patient treated with direct-acting antivirals (DAA)

2019 ◽  
Vol 75 (1) ◽  
pp. 252-253 ◽  
Author(s):  
Cinzia Caudai ◽  
Chiara Papalini ◽  
Daniela Francisci ◽  
Franco Baldelli ◽  
Maurizio Zazzi
Keyword(s):  
Infected Patient ◽  
Late Relapse ◽  
Direct Acting Antivirals ◽  
Genotype 3 ◽  
Hcv Genotype ◽  
Hcv Genotype 3 ◽  
Direct Acting
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