Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics

Osinusi, A.; Meissner, Eric G.; Lee, Yu Jin; Bon, Dimitra; Heytens, Laura; Nelson, Amy; Sneller, Michael C.; Kohli, Anita; Barrett, Lisa; Proschan, Michael A.; Herrmann, Eva; Shivakumar, Bhavana; Gu, Wenjuan; Kwan, Richard; Teferi, Geb; Talwani, Rohit; Silk, Rachel; Kotb, Colleen; Wróblewski, Susan; Fishbein, Dawn; Dewar, Robin; Highbarger, Helene; Zhang, Xiao; Kleiner, David E.; Wood, Bradford J.; Chávez, José; Symonds, William T.; Subramanian, Mani; McHutchison, John G.; Polis, Michael A.; Fauci, Anthony S.; Masur, Henry; Kottilil, Shyamasundaran

doi:10.1001/jama.2013.109309

Cited by 271 publications

(287 citation statements)

References 24 publications

Supporting

Mentioning

271

Contrasting

Unclassified

Order By: Relevance

“…Six trials have addressed the issue of SOF and RBV therapy, with or without Peg-IFNa, in the management of GT-1. These include the NIH SPARE, 30 ELECTRON, 31 NEUTRINO, 19 QUANTUM, 32 ATOMIC, 33 and PROTON 34 trials. All the trials enrolled treatmentnaive patients of GT-1, except for the one arm of treatment-experienced GT-1 patients in the ELECTRON trial (n = 10).…”

Section: Ns5b-i Ravsmentioning

confidence: 99%

“…In the NIH SPARE trial, Osinusi et al 30 evaluated the role of SOF and RBV in 60 treatment-naive patients with HCV GT-1 with unfavorable characteristics (e.g. African American race and advanced fibrosis).…”

Section: Ns5b-i Ravsmentioning

confidence: 99%

“…31 Genotype 1 with advanced fibrosis and cirrhosis: In the NIH SPARE trial, 7 of the 13 participants (54%) with advanced liver fibrosis treated in this study relapsed including all 4 patients with cirrhosis. 30 SOF used as a single DAA along with RBV has poor results for GT-1 HCV infection. The results of SOF and RBV therapy in prior treatment failures and in cirrhotics are even worse.…”

Section: Ns5b-i Ravsmentioning

confidence: 99%

See 2 more Smart Citations

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects. ( J CLIN EXP HEPATOL 2016;6:119-145) T here have been revolutionary changes in the management of chronic hepatitis C (CH-C) over the last few years. Pegylated interferon alfa (Peg-IFNa) plus ribavirin (RBV) therapy, which till the recent past was the standard of care, has been eclipsed by the arrival of newer directly acting antiviral agents (DAAs). Not only do the DAAs have better efficacy, they are also associated with lower side effects, have better tolerability, a shorter duration of therapy, and have simpler administration.In the recent guidelines issued by the American Association for the study of Liver Diseases (AASLD), in collaboration with the Infectious Diseases Society of America 1 and the European Association for Study of the Liver z (EASL), 2 the role of Peg-IFNa/RBV therapy in the management of HCV has been relegated to second-line, backup status. These newer guidelines, however, cannot be implemented in India as many of the recommended drugs are yet to be marketed in India. Other considerations for the treatment of HCV in India are a predominance of

show abstract

Section: Ns5b-i Ravsmentioning

confidence: 99%

Section: Ns5b-i Ravsmentioning

confidence: 99%

Section: Ns5b-i Ravsmentioning

confidence: 99%

See 1 more Smart Citation

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Puri

Saraswat

Dhiman

et al. 2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

show abstract

“…Boceprevir and telaprevir protease inhibitors have been shown to exhibit significantly higher rates of SVR against HCV genotype 1 (65%-75%) as compared with peginterferon-ribavirin alone [10,11] . More recently, sofosbuvir has also been used for treatment along with ribavirin, with significant increased SVR [61] . However, use of these antiviral agents display higher incidence of adverse events, such as rash, gastrointestinal disorders, and anemia.…”

Section: Therapeutic Approaches and Future Goalsmentioning

confidence: 99%

Hepatitis C virus infection and insulin resistance

Bose¹

2014

WJD

View full text Add to dashboard Cite

Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is the primary cause for liver transplantation in the western world. Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of type Ⅱ diabetes. Insulin resistance plays an important role in the development of various complications associated with HCV infection. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral treatment. Thus, HCV associated insulin resistance is a therapeutic target at any stage of HCV infection. HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway. Various mechanisms have been proposed in regard to HCV mediated insulin resistance, involving up regulation of inflammatory cytokines, like tumor necrosis factor-α, phosphorylation of insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of lipid droplets. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Hepatitis C virus; Insulin resistance; Insulin receptor substrate 1; Protein kinase B; mammalian target of rapamycin/S6K1; Suppressor of cytokine signaling 3; Glucose transporter-4; Lipid metabolism; Antiviral therapy Core tip: Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection and often leads to development of type Ⅱ diabetes. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, hepatocellular carcinoma and resistance to anti-viral treatment. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways.Bose SK, Ray R. Hepatitis C virus infection and insulin resistance. World J Diabetes 2014; 5(1): 52-58 Available from: URL:

show abstract

“…6 The early promise of 2′CMe-7-deaza-adenosine ( Figure 1) and, more recently, the excellent clinical success of sofosbuvir have validated the use of NIs as anti-HCV DAAs. 5,7,8 Structural analogues that have attracted relatively little attention to date for application to HCV are C-nucleosides, 9−14 which comprise a sugar moiety and non-natural heterocylic base connected by a carbon−carbon bond. This strong glycosidic bond makes C-nucleosides more resistant to enzymatic and hydrolytic cleavage than their N-nucleoside counterparts.…”

Section: H Epatitis C Virus (Hcv) Is a Major Cause Of Chronic Viralmentioning

confidence: 99%

Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents

Draffan¹,

Frey²,

Pool³

et al. 2014

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Nucleoside analogues have long been recognized as prospects for the discovery of direct acting antivirals (DAAs) to treat hepatitis C virus because they have generally exhibited crossgenotype activity and a high barrier to resistance. C-Nucleosides have the potential for improved metabolism and pharmacokinetic properties over their N-nucleoside counterparts due to the presence of a strong carbon−carbon glycosidic bond and a non-natural heterocyclic base. Three 2′CMe-C-adenosine analogues and two 2′CMe-guanosine analogues were synthesized and evaluated for their anti-HCV efficacy. The nucleotide triphosphates of four of these analogues were found to inhibit the NS5B polymerase, and adenosine analogue 1 was discovered to have excellent pharmacokinetic properties demonstrating the potential of this drug class.

show abstract

Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics

Cited by 271 publications

References 24 publications

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

Hepatitis C virus infection and insulin resistance

Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents

Contact Info

Product

Resources

About