Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial
TL;DR: 8 weeks of grazoprevir plus elbasvir was highly effective for the treatment of acute HCV genotype 1 or 4 infection and whether treatment can be shortened during the acute phase of HCV infection is investigated.
About: This article is published in The Lancet Gastroenterology & Hepatology.The article was published on 2019-04-01. It has received 31 citations till now. The article focuses on the topics: Grazoprevir & Elbasvir.
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TL;DR: The Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era.
59 citations
TL;DR: There has been a 78% reduction in the incidence of first HCV episode and a 68% reduce in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England.
Abstract: Background Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom. Methods A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated. Results A total of. 378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95-18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018). Conclusions We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population.
36 citations
Cites background from "Treatment of acute hepatitis C geno..."
...trials demonstrating high efficacy with shortened courses of treatment [5, 6]....
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TL;DR: In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections as discussed by the authors .
Abstract: In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
23 citations
TL;DR: Among treatment‐naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended.
21 citations
Cites background from "Treatment of acute hepatitis C geno..."
...To date, the largest trial of DAA therapy among people with acute HCV showed high efficacy with 8 weeks of grazoprevir/elbasvir among people with HCV genotypes 1 and 4 (n = 80, sustained virologic response at 12 weeks posttreatment [SVR12] intention to treat [ITT] 94%).(6) Glecaprevir/pibrentasvir is a highly effective pangenotypic DAA regimen prescribed for 8 weeks in treatment-naive individuals with chronic HCV and without cirrhosis....
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...9 4 infection, high efficacy was reported with 6 weeks of sofosbuvir/ledipasvir (n = 20, SVR12 ITT 100%; HCV monoinfection only)(13) and 8 weeks of grazoprevir/elbasvir (n = 80, SVR12 ITT 94%, SVR12 PP 99%),(6) paritaprevir/ritonavir/ombitasvir/dasabuvir (n = 30, SVR12 ITT 97%, SVR12 PP 100%),(14) and sofosbuvir/ledipasvir (n = 27, SVR12 ITT 100%)....
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24 Jul 2020
TL;DR: New CDC guidance is established that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV) that reflects updated guidance from professional organizations that recommend treatment for acute HCV infection.
Abstract: Exposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be performed as soon as possible (preferably within 48 hours) after the exposure. A source patient refers to any person receiving health care services whose blood or other potentially infectious material is the source of the HCP's exposure. Two options are recommended for testing the source patient. The first option is to test the source patient with a nucleic acid test (NAT) for HCV RNA. This option is preferred, particularly if the source patient is known or suspected to have recent behaviors that increase risk for HCV acquisition (e.g., injection drug use within the previous 4 months) or if risk cannot be reliably assessed. The second option is to test the source patient for antibodies to hepatitis C virus (anti-HCV), then if positive, test for HCV RNA. For HCP, baseline testing for anti-HCV with reflex to a NAT for HCV RNA if positive should be conducted as soon as possible (preferably within 48 hours) after the exposure and may be simultaneous with source-patient testing. If follow-up testing is recommended based on the source patient's status (e.g., HCV RNA positive or anti-HCV positive with unavailable HCV RNA or if the HCV infection status is unknown), HCP should be tested with a NAT for HCV RNA at 3-6 weeks postexposure. If HCV RNA is negative at 3-6 weeks postexposure, a final test for anti-HCV at 4-6 months postexposure is recommended. A source patient or HCP found to be positive for HCV RNA should be referred to care. Postexposure prophylaxis of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids. This guidance was developed based on expert opinion (CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommend Rep 2001;50[No. RR-11]; Supplementary Figure, https://stacks.cdc.gov/view/cdc/90288) and reflects updated guidance from professional organizations that recommend treatment for acute HCV infection. Health care providers can use this guidance to update their procedures for postexposure testing and clinical management of HCP potentially exposed to hepatitis C virus.
15 citations
References
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TL;DR: Treatment of acute hepatitis C with interferon alfa-2b with treatment during the acute phase could prevent the development of chronic infection.
Abstract: Background In people who are infected with the hepatitis C virus (HCV), chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection. Methods Between 1998 and 2001, we identified 44 patients throughout Germany who had acute hepatitis C. Patients received 5 million U of interferon alfa-2b subcutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. Results The mean age of the 44 patients was 36 years; 25 were women. Nine became infected with HCV through intravenous drug use, 14 through a needle-stick injury, 7 through medical procedures, and 10 through sexual contact; the mode of infection could not be determined in 4. The average time from infection to the first signs or symptoms of hepatitis was 54 days, and the average time from infection until the start of therapy ...
782 citations
TL;DR: The development of an automated genotyping system that can be easily applied to HIV-1 and other rapidly evolving viral pathogens is described.
Abstract: Motivation: Genetic analysis of HIV-1 is important not only for vaccine development, but also to guide treatment strategies, track the emergence of new viral variants and ensure that diagnostic assays are contemporary and fully optimized. However, most genotyping methods are laborious and complex, and involve the use of multiple software applications. Here, we describe the development of an automated genotyping system that can be easily applied to HIV-1 and other rapidly evolving viral pathogens.
Results: The new REGA subtyping tool, developed using Java programming and PERL scripts, combines phylogenetic analyses with bootscanning methods for the genetic subtyping of full-length and subgenomic fragments of HIV-1. When used to investigate the subtype of previously published reference datasets that were analysed using manual phylogenetic methods, the automated method correctly identified 97.5--100% of non-recombinant and circulating recombinant forms of HIV-1, including 108 full-length, 108 gag and 221 env sequences downloaded from the Los Alamos database.
Availability: The tool, which can be easily downloaded and installed on either a UNIX or Linux-based computer system, is available at http://www.bioafrica.net/subtypetool/html/
Contact: tulio.deoliveira@zoology.oxford.ac.uk
509 citations
TL;DR: Grazoprevir and elbasvir were evaluated in a randomized, blinded, placebo-controlled trial in treatment-naive patients with hepatitis C virus (HCV) infection.
Abstract: BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.
446 citations
Journal Article•
TL;DR: This phase 3 trial found a once-daily grazoprevirelbasvir regimen to be effective and well-tolerated in patients with HCV genotype 1, 4, or 6 infection and represents a new therapeutic option for chronic HCV infection.
Abstract: Various oral interferon- and ribavirin-free regimens are becoming available to treat chronic hepatitis C virus (HCV) infection. This phase 3 trial evaluates the effectiveness and tolerability of a ...
300 citations
TL;DR: The C-WORTHY trial as mentioned in this paper evaluated the efficacy and safety of a combination of grazoprevir plus elbasvir with or without ribavirin in patients with hepatitis C virus (HCV) mono-infection and co-infected patients.
250 citations