scholarly journals Hepatitis C Virus RNA Levels Following Virologic Failure With Direct-acting Antivirals: Implications for Lower Sensitivity Diagnostic Assays

2019 ◽  
Vol 70 (2) ◽  
pp. 327-330 ◽  
Author(s):  
Patrick R Harrington ◽  
Takashi E Komatsu ◽  
Hengrui Sun ◽  
Lisa K Naeger
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virologic Failure ◽  
Post Treatment ◽  
Hcv Rna ◽  
Lower Sensitivity ◽  
Direct Acting Antivirals ◽  
Diagnostic Assays ◽  
Direct Acting ◽  
Rna Levels

Abstract We analyzed post-treatment hepatitis C virus (HCV) RNA levels from 330 subjects who experienced virologic failure in clinical trials of direct-acting antivirals. We demonstrated that 97% had post-treatment Week 12 HCV RNA >10 000 IU/mL, above reported sensitivity limits of novel diagnostic assays being considered for simplified HCV treatment monitoring.

scholarly journals Characterization of Hepatitis C Virus Resistance from a Multiple-Dose Clinical Trial of the Novel NS5A Inhibitor GS-5885

2013 ◽  
Vol 57 (12) ◽  
pp. 6333-6340 ◽  
Author(s):  
Kelly A. Wong ◽  
Angela Worth ◽  
Ross Martin ◽  
Evguenia Svarovskaia ◽  
Diana M. Brainard ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Rna ◽  
Direct Acting Antivirals ◽  
Phenotypic Analysis ◽  
Median Viral Load ◽  
Ns5a Inhibitor ◽  
Treatment Naïve ◽  
Direct Acting

ABSTRACTGS-5885 is a novel hepatitis C virus (HCV) NS5A inhibitor. In a 3-day monotherapy study in treatment-naive genotype 1a (GT1a) and GT1b HCV-infected subjects, median viral load reductions ranged from 2.3 to 3.3 log10HCV RNA IU/ml across dosing cohorts (1, 3, 10, 30, or 90 mg once daily). Here, we report viral sequencing and phenotypic analysis of clinical isolates from this study. Detection of baseline NS5A amino acid substitutions at positions 28, 30, 31, or 93 in GT1a was associated with a reduced treatment response. In the GT1b cohort, Y93H was detected in 100% of subjects at day 4 or 14. In the Gt1a cohort, population sequencing detected NS5A resistance-associated mutations at day 4 or 14 for 3/10 subjects at the 1-mg dose and for all subjects dosed at ≥3 mg. A subset of mutants that confer a low level of reduced susceptibility to GS-5885 was not detected by population sequencing at the 30- and 90-mg doses. Subject-derived M28T, Q30R, L31M, and Y93C mutations all conferred >30-fold reductions in GS-5885 and daclatasvir susceptibilitiesin vitro. Site-directed NS5A mutants also showed reduced susceptibility to GS-5885. However, all NS5A mutants tested remained fully susceptible to other classes of direct-acting antivirals (DAAs), interferon alpha, and ribavirin. Importantly, the nonoverlapping resistance profile and high potency of GS-5885 support its further development with other direct-acting antivirals for the treatment of chronic HCV. (This study has been registered at ClinicalTrials.gov under registration number NCT01193478.)

scholarly journals Hepatitis C Virus Core Antigen as an Alternative to RNA in the Assessment of Response to Treatment with Direct-acting Oral Antivirals

2021 ◽  
Vol 21 (9) ◽  
Author(s):  
Antonio Mancebo Martínez ◽  
Paula Núñez Serrano ◽  
José Carlos Fernández de Cañete Camacho ◽  
José María Moreno Planas
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Strong Correlation ◽  
Predictive Value ◽  
Core Antigen ◽  
Hcv Rna ◽  
Molecular Testing ◽  
The Mean ◽  
Direct Acting ◽  
Rna Levels

Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg < 3 fmol/L and RNA < 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P < 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P < 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.

scholarly journals Visualization of Positive and Negative Sense Viral RNA for Probing the Mechanism of Direct-Acting Antivirals against Hepatitis C Virus

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1039
Author(s):  
Dandan Liu ◽  
Philip R. Tedbury ◽  
Shuiyun Lan ◽  
Andrew D. Huber ◽  
Maritza N. Puray-Chavez ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Viruses ◽  
Drug Efficacy ◽  
Confocal Imaging ◽  
Hcv Rna ◽  
Direct Acting Antivirals ◽  
Infected Cells ◽  
Positive Strand Rna ◽  
Direct Acting

RNA viruses are highly successful pathogens and are the causative agents for many important diseases. To fully understand the replication of these viruses it is necessary to address the roles of both positive-strand RNA ((+)RNA) and negative-strand RNA ((−)RNA), and their interplay with viral and host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) to stain both the abundant (+)RNA and the far less abundant (−)RNA in both hepatitis C virus (HCV)- and Zika virus-infected cells, and combined these analyses with visualization of viral proteins through confocal imaging. We were able to phenotypically examine HCV-infected cells in the presence of uninfected cells and revealed the effect of direct-acting antivirals on HCV (+)RNA, (−)RNA, and protein, within hours of commencing treatment. Herein, we demonstrate that bDNA FISH is a powerful tool for the study of RNA viruses that can provide insights into drug efficacy and mechanism of action.

scholarly journals Real-world efficacy and safety of pangenotypic direct-acting antivirals against hepatitis C virus infection in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kao-Chi Chang ◽  
Shui-Yi Tung ◽  
Kuo-Liang Wei ◽  
Chen-Heng Shen ◽  
Yung-Yu Hsieh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real World ◽  
Population Analysis ◽  
Virologic Response ◽  
Efficacy And Safety ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antivirals ◽  
Evaluable Population ◽  
Direct Acting

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.

scholarly journals Risk of extrahepatic cancer in a nationwide cohort of hepatitis C virus infected persons treated with direct acting antivirals

GastroHep ◽  
2021 ◽  
Author(s):  
Charlotte Lybeck ◽  
Daniel Bruce ◽  
Scott M Montgomery ◽  
Soo Aleman ◽  
Ann‐Sofi Duberg
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Direct Acting Antivirals ◽  
Direct Acting
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