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Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.

ABSTRACT: BACKGROUND:High sustained virological response at 12?weeks after end of treatment (SVR12) with 12?weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1. METHODS:We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12?weeks of SMV+SOF±RBV. Original studies with SVR12 data in ?5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p?0.10 and I(2) statistic ?50%. RESULTS:Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728). CONCLUSIONS:SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.

SUBMITTER: Yee BE

PROVIDER: S-EPMC4780041 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.

Yee Brittany E BE Nguyen Nghia H NH Jin Minjuan M Lutchman Glen G Lim Joseph K JK Nguyen Mindie H MH

BMJ open gastroenterology 20160302 1

<h4>Background</h4>High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1.<h4>Methods</h4>We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and obse ...[more]

PMID: 26966547

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Project description:ImportanceThere is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV).ObjectiveTo evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir.Design, setting, and participantsOpen-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed.InterventionsFifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks.Main outcomes and measuresThe primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment.ResultsForty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug.Conclusions and relevanceIn this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.Trial registrationclinicaltrials.gov Identifier:NCT01878799.

Dataset Information

Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.

Publications

Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.

Similar Datasets

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