Document Detail


Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C.
MedLine Citation:
PMID:  23281974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.
METHODS: We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy.
RESULTS: Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia.
CONCLUSIONS: Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number, NCT01260350.).
Authors:
Edward J Gane; Catherine A Stedman; Robert H Hyland; Xiao Ding; Evguenia Svarovskaia; William T Symonds; Robert G Hindes; M Michelle Berrey
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  368     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-01-17     Revised Date:  2014-01-03    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34-44     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT01260350
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antiviral Agents / adverse effects,  therapeutic use*
Drug Therapy, Combination
Female
Genotype
Hemoglobins / metabolism
Hepacivirus / genetics,  isolation & purification
Hepatitis C, Chronic / blood,  drug therapy*
Humans
Interferon-alpha / adverse effects,  therapeutic use
Male
Middle Aged
Polyethylene Glycols / adverse effects,  therapeutic use
RNA, Viral / metabolism
Recombinant Proteins / adverse effects,  therapeutic use
Ribavirin / adverse effects,  therapeutic use*
Uridine Monophosphate / adverse effects,  analogs & derivatives*,  therapeutic use
Viral Load
Viral Nonstructural Proteins / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/2-((5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-ylmethoxy)phenoxyphosphorylamino)propionic acid isopropyl ester; 0/Antiviral Agents; 0/Hemoglobins; 0/Interferon-alpha; 0/NS-5 protein, hepatitis C virus; 0/Polyethylene Glycols; 0/RNA, Viral; 0/Recombinant Proteins; 0/Viral Nonstructural Proteins; 0/peginterferon alfa-2a; 49717AWG6K/Ribavirin; E2OU15WN0N/Uridine Monophosphate
Comments/Corrections
Comment In:
J Hepatol. 2013 Dec;59(6):1342-5   [PMID:  23891655 ]
Gastroenterology. 2013 Jul;145(1):245-7   [PMID:  23721818 ]
N Engl J Med. 2013 May 16;368(20):1931-2   [PMID:  23607592 ]

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