scholarly journals Efficacy and safety of ledipasvir/sofosbuvir in 5,028 Mongolian patients infected with genotype 1 hepatitis C virus: A multicenter study

2021 ◽  
Vol 27 (1) ◽  
pp. 125-135
Author(s):  
Oidov Baatarkhuu ◽  
Jae Seung Lee ◽  
Jazag Amarsanaa ◽  
Do Young Kim ◽  
Sang Hoon Ahn ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real World ◽  
Virologic Response ◽  
Hcv Rna ◽  
Efficacy And Safety ◽  
Genotype 1 ◽  
High Efficacy ◽  
Genotype 1A ◽  
End Of Treatment

Background/Aims: Ledipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients.Methods: Between 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12).Results: Most patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×10<sup>6</sup> IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%).Conclusions: LDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

scholarly journals Efficacy and Safety of Danoprevir-Ritonavir plus Peginterferon Alfa-2a–Ribavirin in Hepatitis C Virus Genotype 1 Prior Null Responders

2013 ◽  
Vol 58 (2) ◽  
pp. 1136-1145 ◽  
Author(s):  
Edward J. Gane ◽  
Régine Rouzier ◽  
Alicja Wiercinska-Drapalo ◽  
Dominique G. Larrey ◽  
Peter N. Morcos ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Hcv Rna ◽  
Efficacy And Safety ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Peginterferon Alfa

ABSTRACTDanoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a–ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a–ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a–ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a–ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had anIL28Bnon-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a–ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered atClinicalTrials.govunder registration no. NCT01185860.)

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 In VitroandIn VivoAntiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450

2014 ◽  
Vol 59 (2) ◽  
pp. 988-997 ◽  
Author(s):  
Tami Pilot-Matias ◽  
Rakesh Tripathi ◽  
Daniel Cohen ◽  
Isabelle Gaultier ◽  
Tatyana Dekhtyar ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Cross Resistance ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Common Amino Acid ◽  
Direct Acting Antiviral ◽  
Genotype 1A

ABSTRACTThe development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively.In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log10was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. NCT01074008.)

scholarly journals Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
John A. Howe ◽  
Jianmin Long ◽  
Stuart Black ◽  
Robert Chase ◽  
Patricia McMonagle ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Failure ◽  
Virologic Response ◽  
Phase Iii ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Virus Genotype ◽  
The Impact

Abstract Background.  We analyzed the impact of pretreatment variants conferring boceprevir-resistance on sustained virologic response (SVR) rates achieved with boceprevir plus peginterferon-α/ribavirin (P/R) for hepatitis C virus (HCV)-genotype-1 infection. Methods.  NS3-protease-polymorphisms emerging coincident with virologic failure on boceprevir/P/R regimens were identified as resistance-associated variants (RAVs). Baseline samples pooled from 6 phase II or phase III clinical trials were analyzed for RAVs by population sequencing. Interferon (IFN)-responsiveness was predefined as &gt;1 log reduction in HCV-RNA level during the initial 4-week lead-in treatment with P/R before boceprevir was added. The effective boceprevir-concentration inhibiting RAV growth by 50% (EC50) was determined using a replicon assay relative to the wild-type referent. Results.  Sequencing was performed in 2241 of 2353 patients (95.2%) treated with boceprevir. At baseline, RAVs were detected in 178 patients (7.9%), including 153 of 1498 genotype-1a infections (10.2%) and 25 of 742 genotype-1b infections (3.4%) (relative risk, 3.03; 95% confidence interval [CI], [2.01, 4.58]). For IFN-responders, SVR24 (SVR assessed 24 weeks after discontinuation of all study medications) rates were 78% and 76% with or without RAVs detected at baseline, respectively. For the 510 poor IFN-responders, SVR24 rates were 8 of 36 subjects (22.2% [11.7%, 38.1%]) when baseline RAVs were detected vs 174 of 474 subjects (36.7% [32.5%, 41.1%]) when baseline RAVs were not detected (relative likelihood of SVR24 [95% CI], 0.61 [0.32, 1.05]). Sustained virologic response was achieved in 7 of 8 (87.5%) IFN-nonresponders with baseline variants exhibiting ≤2-fold increased EC50 for boceprevir in a replicon assay, whereas only 1 of 15 (7%) IFN-nonresponders with baseline RAVs associated with ≥3-fold increased EC50 achieved SVR. Conclusions.  Baseline protease-variants appear to negatively impact SVR rates for boceprevir/P/R regimens only when associated with decreased boceprevir susceptibility in vitro after a poor IFN-response during the lead-in period.

scholarly journals Real-World Effectiveness of Simeprevir-containing Regimens Among Patients With Chronic Hepatitis C Virus: The SONET Study

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
Imtiaz Alam ◽  
Kimberley Brown ◽  
Cynthia Donovan ◽  
Jamie Forlenza ◽  
Kris Lauwers ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real World ◽  
Virologic Response ◽  
Hcv Infection ◽  
Serious Adverse Events ◽  
The Real ◽  
End Of Treatment ◽  
Viral Relapse ◽  
Intent To Treat

Abstract Background The Simeprevir ObservatioNal Effectiveness across practice seTtings (SONET) study evaluated the real-world effectiveness of simeprevir-based treatment for hepatitis C virus (HCV) infection. Methods The SONET study was a phase 4, prospective, observational, United States–based study enrolling patients ≥18 years of age with chronic genotype 1 HCV infection. The primary endpoint was the proportion of patients who achieved sustained virologic response 12 weeks after the end of treatment (SVR12), defined as HCV ribonucleic acid undetectable ≥12 weeks after the end of all HCV treatments. Results Of 315 patients (intent-to-treat [ITT] population), 275 (87.3%) completed the study. Overall, 291 were treated with simeprevir + sofosbuvir, 17 with simeprevir + sofosbuvir + ribavirin, and 7 with simeprevir + peginterferon + ribavirin. The majority of patients were male (63.2%) and white (60.6%); median age was 58 years, 71.7% had genotype/subtype 1a, and 39.4% had cirrhosis. The SVR12 was achieved by 81.2% (255 of 314) of ITT patients (analysis excluded 1 patient who completed the study but was missing SVR12 data); 2 had viral breakthrough and 18 had viral relapse. The SVR12 was achieved by 92.4% (255 of 276) of patients in the modified ITT (mITT) population, which excluded patients who discontinued treatment for nonvirologic reasons before the SVR12 time point or were missing SVR12 assessment data. Among mITT patients, higher SVR12 rates were associated with factors including age ≥65 years, non-Hispanic/Latino ethnicity, and employment status, but not genotype/subtype nor presence of cirrhosis. Simeprevir-based treatment was well tolerated; no serious adverse events were considered related to simeprevir. Conclusions In the real-world setting, simeprevir + sofosbuvir treatment was common and 92% of mITT patients achieved SVR12. Simeprevir-based treatment was effective and well tolerated in this cohort, including patients with cirrhosis.

scholarly journals Plasma Ribavirin Trough Concentrations at Week 4 Predict Hepatitis C Virus (HCV) Relapse in HIV-HCV-Coinfected Patients Treated for Chronic Hepatitis C

2010 ◽  
Vol 54 (4) ◽  
pp. 1647-1649 ◽  
Author(s):  
Judit Morello ◽  
Vincent Soriano ◽  
Pablo Barreiro ◽  
José Medrano ◽  
Antonio Madejón ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Odds Ratio ◽  
Hcv Rna ◽  
Genotype 1 ◽  
Baseline Serum ◽  
End Of Treatment ◽  
Trough Concentrations ◽  
Hcv Genotype 1

ABSTRACT The influence of ribavirin trough concentrations (RBV C trough) on the risk of hepatitis C virus (HCV) relapse was retrospectively analyzed in 99 HIV-HCV-coinfected patients who achieved end-of-treatment response with pegylated alpha interferon plus weight-based RBV. The independent predictors (odds ratio [OR] [95% confidence interval (CI)]) of HCV relapse were RBV plasma C trough of <2.5 μg/ml (4.5 [1.3 to 15.5]), baseline serum HCV RNA (2.5 [1.2 to 5.1]), and HCV genotype 1 or 4 (13.3 [2.6 to 66.7]). Monitoring of RBV C trough may permit early adjustment of RBV dosage to avoid HCV relapse.

scholarly journals Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Yinan Yao ◽  
Ming Yue ◽  
Jie Wang ◽  
Hongbo Chen ◽  
Mei Liu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Efficacy And Safety ◽  
Genotype 1 ◽  
Hcv Genotype ◽  
Link Type ◽  
End Of Treatment ◽  
Treatment Naïve ◽  
Previously Treated Patients ◽  
Hcv Genotype 1

Background. It is urgent for patients with hepatitis C virus (HCV) infection to find a safe, effective, and interferon-free regimen to optimize therapy. A comprehensive analysis was performed to evaluate the efficacy and safety of the grazoprevir combined with elbasvir, with or without ribavirin (RBV), in 777 treatment-naive and treatment-experienced patients with HCV genotype 1 infection from 3 randomized controlled trials (RCTs). Method. We collected data from the following trials: C-WORTHY (NCT01717326), C-SALVAGE (NCT02105454), and C-EDGE (NCT02105467). All patients received grazoprevir plus elbasvir with or without RBV for 12 or 18 weeks. The sustained virological response (SVR) 12 weeks after end of treatment was calculated for overall and subgroups. Results. 568 (73%) patients were treatment-naive. Overall, 95% (95% CI: 93–96) patients achieved SVR12, 95% (95% CI: 92–96) for treatment-naive and 96% (95% CI: 92–98) for previously treated patients, respectively. Treatment duration and treatment regimen did not have great difference in SVR12 rates. The most common AEs were fatigue (18%–29%), headache (20%), nausea (8%–14%), and asthenia (4%–12%). One patient (<1%) receiving grazoprevir plus elbasvir alone and one (<1%) receiving grazoprevir plus elbasvir plus RBV had treatment-related serious AEs. Conclusions. The result shows that 12-week grazoprevir plus elbasvir therapy is safe and effective for treatment-naive patients with HCV genotype 1.

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