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Teo C.-G.,Centers for Disease Control and Prevention | Locarnini S.A.,Victorian Infectious Diseases Reference Laboratory
Antiviral Therapy | Year: 2010

Immune pressure exerted on HBV by anti-HBV antibodies and long-term therapy with drugs that mutagenize the viral P gene can select for mutations in its S gene, leading to vaccine escape and evasion from serological detection. Although transmissibility of these mutants is poor and their evolution towards heightened virulence appears slow, the situation could change as vaccination coverage increases, and treatment of patients with chronic hepatitis B and those coinfected by HIV and HBV becomes widespread. Enhanced surveillance programmes to track changes in the genotype and phenotype of the mutants are needed. ©2010 International Medical Press. Source


Gish R.,University of California at San Diego | Jia J.-D.,Capital Medical University | Locarnini S.,Victorian Infectious Diseases Reference Laboratory | Zoulim F.,French Institute of Health and Medical Research | Zoulim F.,Institut Universitaire de France
The Lancet Infectious Diseases | Year: 2012

Antiviral drug resistance is a crucial factor that frequently determines the success of long-term therapy for chronic hepatitis B. The development of resistance to nucleos(t)ide analogues has been associated with exacerbations in liver disease and increased risk of emergence of multidrug resistance. The selection of a potent nucleos(t)ide analogue with a high barrier to resistance as a first-line therapy, such as entecavir or tenofovir, provides the best chance of achieving long-term treatment goals and should be used wherever possible. The barrier to resistance of a given nucleos(t)ide analogue is influenced by genetic barrier, drug potency, patient adherence, pharmacological barrier, viral fitness, mechanism of action, and cross-resistance. In countries with limited health-care resources, the selection of a therapy with a high barrier to resistance is not always possible and alternative strategies for preventing resistance might be needed, although limited data are available to support these strategies. © 2012 Elsevier Ltd. Source


Zoulim F.,French Institute of Health and Medical Research | Zoulim F.,University of Lyon | Zoulim F.,Institut Universitaire de France | Locarnini S.,Victorian Infectious Diseases Reference Laboratory
Journal of Hepatology | Year: 2012

Antiviral therapy of chronic hepatitis B remains a clinical challenge. The primary goal of therapy is to prevent liver disease progression. Because of the mechanism of viral persistence in infected hepatocytes, long-term antiviral therapy is needed in the majority of patients. Incomplete viral suppression and emergence of drug resistance is a major concern. The correct choice of a first-line potent therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance, such as entecavir and tenofovir, have significantly lower rates of resistance when compared with those with a low barrier to resistance such as lamivudine, adefovir, or telbivudine. Management of treatment failure requires a precise clinical and accurate virologic monitoring as well as an early treatment intervention with appropriate complementary drugs with respect to their cross-resistance profile. Long-term surveillance for treatment efficacy and possible emergence of drug resistance is necessary for those patients who have been sequentially treated with multiple antivirals. Finally, the identification of novel treatment targets remains a major research challenge to improve the efficacy of current antiviral therapy. © 2012 European Association for the Study of the Liver. Source


Marshall J.A.,Victorian Infectious Diseases Reference Laboratory
International journal of environmental research and public health | Year: 2011

Noroviruses are a major cause of gastroenteritis outbreaks worldwide. Norovirus outbreaks frequently occur as epidemics which appear to be related to both genetic and environmental factors. This review considers recent progress in understanding these factors. The norovirus genome undergoes continuous change and this appears to be important in the persistence of the virus in the community. Studies on the common GII.4 genotype have shown that some norovirus outbreak epidemics involving this genotype are correlated with specific changes in the genome. In contrast to the growing understanding of the role of genetic factors in norovirus outbreak epidemics, the role of environmental factors is less well understood. Topics reviewed here include long term excretion of norovirus in some individuals, long term survivability of norovirus in the environment, the role of meteorological factors in the control of norovirus outbreaks and the possible zoonotic transmission of the virus. Source


Zoulim F.,University of Lyon | Locarnini S.,Victorian Infectious Diseases Reference Laboratory
Liver International | Year: 2013

The management of treatment failure in patients with chronic hepatitis B, remains a clinical concern. Incomplete viral suppression and the emergence of drug resistance are key determinants of treatment failure. The correct choice of a potent first-line therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross-resistant antivirals. Long-term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. The identification of novel treatment targets remains a major research goal to improve the efficacy of current antiviral therapy through combination therapy regimens. © 2012 John Wiley & Sons A/S. Source

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