Article

A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients.

National Cheng Kung University Medical College, Tainan, Taiwan.
Gastroenterology (impact factor: 11.68). 11/2005; 129(4):1198-209. DOI:10.1053/j.gastro.2005.06.055 pp.1198-209
Source: PubMed

ABSTRACT Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients.
Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for > or =24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks.
At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%; P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log(10) copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log(10) copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group).
In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.

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    Article: Comparison of the Mechanisms of Drug Resistance among HIV, Hepatitis B, and Hepatitis C.
    Severine Margeridon-Thermet, Robert W Shafer
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    ABSTRACT: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the most prevalent deadly chronic viral diseases. HIV is treated by small molecule inhibitors. HBV is treated by immunomodulation and small molecule inhibitors. HCV is currently treated primarily by immunomodulation but many small molecules are in clinical development. Although HIV is a retrovirus, HBV is a double-stranded DNA virus, and HCV is a single-stranded RNA virus, antiviral drug resistance complicates the development of drugs and the successful treatment of each of these viruses. Although their replication cycles, therapeutic targets, and evolutionary mechanisms are different, the fundamental approaches to identifying and characterizing HIV, HBV, and HCV drug resistance are similar. This review describes the evolution of HIV, HBV, and HCV within individuals and populations and the genetic mechanisms associated with drug resistance to each of the antiviral drug classes used for their treatment.
    Viruses 12/2010; 2(12):2696-739. · 1.50 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

alanine aminotransferase levels
 
branched chain DNA assay
 
documented lamivudine resistance substitutions
 
entecavir
 
entecavir 0.5 mg
 
entecavir 1.0
 
entecavir 1.0 mg
 
HBeAg-negative lamivudine-refractory patients
 
HBV
 
HBV DNA levels
 
Hepatitis B e antigen
 
higher proportions
 
lamivudine treatment
 
lamivudine-refractory patients
 
lamivudine-resistant hepatitis B virus
 
phase 2 study
 
potent
 
significant reductions
 
virologic rebound
 
vitro activity