Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental models.
Owing to the persistence of hepatitis B virus (HBV) and the selection of drug-resistant mutants, a new concept of antiviral therapy for chronic hepatitis B relies on the combination of nucleoside analogues. In experimental models of HBV infection, several key points concerning these combinations were addressed. (i) Is it possible to achieve a synergic antiviral effect with polymerase inhibitors? (ii) Is it possible to impact on intracellular viral covalently closed circular DNA? (iii) What is the impact of the cross-resistance patterns of the different nucleoside analogues? (iv) What is the effect of viral load suppression on the restoration of specific antiviral cellular responses? The clinical impact of these key issues is discussed in the perspective of new clinical trials.
Zoulim
Fabien
F
INSERM U271, 151 Cours Albert Thomas, 69003 Lyon, France. zoulim@lyon.inserm.fr
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D009705:Nucleosides / Q000737:chemistry* / Q000627:therapeutic use*
D000998:Antiviral Agents; D009705:Nucleosides; D003841:Deoxycytidine; D001086:Arabinofuranosyluracil; D000068679:Emtricitabine; C034935:clevudine