Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection

Kowdley, Kris V.; Sundaram, Vinay; Jeon, Christie Y.; Qureshi, Kamran; Latt, Nyan L.; Sahota, Amandeep; Lott, Stephen; Curry, Michael P.; Tsai, Naoky; Chaiyakunapruk, Nathorn; Lee, Yoori; Petersen, Jörg; Buggisch, Peter

doi:10.1002/hep.29005

Cited by 55 publications

(53 citation statements)

References 23 publications

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“…These results are similar to those reported in the ION‐3 trial, in which 215 patients received SOF/LDV for 8 weeks, with an SVR rate of 94% and a relapse rate of 5% . Real‐world cohort data have also shown the comparable effectiveness of SOF/LDV for 8 and 12 weeks in HCV genotype 1–infected, treatment‐naive patients without cirrhosis . Of note, the proportions of patients with METAVIR F3 fibrosis (or an equivalent by transient elastography) treated with SOF/LDV for 8 weeks were 13% in the ION‐3 trial and <25% in Madrid‐CoRe.…”

Section: Discussionsupporting

confidence: 83%

All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice

et al. 2018

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We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)–coinfected patients treated with interferon‐free direct‐acting antiviral agent–based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention‐to‐treat analysis was 92.0% (95% confidence interval, 90.9%‐93.1%) overall, 93.8% (92.4%‐95.0%) for no cirrhosis, 91.0% (88.8%‐92.9%) for compensated cirrhosis, and 80.8% (73.7%‐86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14‐2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12‐2.41), a baseline cluster of differentiation 4–positive (CD4+) T‐cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35‐3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14‐2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96‐1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76‐4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. Conclusion: In this large real‐world study, direct‐acting antiviral agent–based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus–related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct‐acting antiviral agent–based regimens. (Hepatology 2018;68:32‐47).

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Section: Discussionsupporting

confidence: 83%

All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice

et al. 2018

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“…Rates of virologic breakthrough (reappearance of HCV RNA while on therapy) or relapse (reappearance of HCV RNA after completion of therapy) were low in all four studies, ranging from 0%–6% 31. These findings have been corroborated in several large real-world observational and registry studies ranging from 600 to 14,000 patients 32–40. The efficacy of LDV/SOF for treating adults with CHC from other genotypes has also been supported by multiple Phase II trials,41–47 a Japanese Phase III trial, and real-world data from a French cohort 31…”

Section: Ldv/sof Use In Adultssupporting

confidence: 66%

Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C

Yang

Goel

Ahmed

2018

AHMT

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Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

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“…Our study showed that the percentage of inmates undergoing 8‐week treatment courses was lower than in the general population (0.5% vs 10.5%). Studies that have demonstrated the efficacy of shorter therapies in selected populations without cirrhosis indicate the need to reduce courses of treatment. What is more, the introduction of new drugs such as voxilaprevir, glecaprevir and pibrentasvir in the near future will facilitate the use of these shorter therapies and may be able to avoid the abandonment of treatment among inmates when they are released …”

Section: Discussionmentioning

confidence: 99%

Comparison of effectiveness and discontinuation of interferon‐free therapy for hepatitis C in prison inmates and noninmates

Marco¹,

Roget

Cervantes

et al. 2018

Journal of Viral Hepatitis

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Chronic hepatitis C treatment with direct acting antiviral (DAA) therapy during incarceration is an attractive option, due to its short duration and to the possibility of directly observed treatment or supervision. The aim of this study is to compare the effectiveness and rates of discontinuation of DAA treatment in prisoners and nonprisoners. We studied all patients treated in the 10 prisons of Catalonia and at 3 public hospitals in the Barcelona area between 1 January 2015 and 30 April 2016. We analysed sustained viral response (SVR) and rates of discontinuation through intention-to-treat and modified-intention-to-treat analyses, the latter excluding discontinuations due to release from prison. One hundred and eighty-eight inmates and 862 noninmates were included. Prisoners were significantly younger than nonprisoners, with higher proportions of men, drug users, HIV infection, genotypes 1a and 3 and more treatment with psychiatric drugs. Overall, 98.4% of patients completed treatment. The discontinuation rate was low, but higher in inmates (3.7% vs 1.2% noninmates; P = .003) and in community patients >65 years old (2.8% vs 1.2% in under 65 seconds; P = .008). Among the inmates, 7 (42.8%) discontinuations were due to release. SVR was 93.1% in inmates vs 96.5% in noninmates (P = .08) by intention-to-treat and 95.1% vs 96.5% (P = .37) by modified intention-to-treat. Virologic failure rates were similar (3.8% vs 3% in noninmates; P = .60). SVR, virologic failure and discontinuation rates were similar in inmates and noninmates. Currently, prisons are considered a priority for the implementation of DAA. Improved coordination between penitentiary and community health systems would help to ensure therapeutic continuity in released prisoners.

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Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection

Abstract: An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).

Cited by 55 publications

References 23 publications

All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice

All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice

Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C

Comparison of effectiveness and discontinuation of interferon‐free therapy for hepatitis C in prison inmates and noninmates

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