title: [Analogs combination therapy in chronic hepatitis B: when and how?].
abstract: Hepatitis B virus (HBV) genomic variability is responsible for the complexity of the viral quasi-species and its evolution during the course of infection. The persistence of infected cells promotes the selection of drug-resistant strains. The development of nucleoside analogs without cross-resistance has provided a rationale for combination therapy. De novo combination, with low genetic barrier drugs, prevents the emergence of resistance in the short-term for drugs with a low genetic barrier and improves the control of infection. Long-term studies are needed to determine whether de novo combination is beneficial for analogs with a high genetic barrier as well. The add-on strategy is a standard in case of emergence of resistant mutants. This strategy needs to be implemented as early as possible before the virological breakthrough, especially if the viral suppression is sub-optimal. Clinical trials are mandatory in order to assess whether a) de novo combination is better than an early add-on strategy; and b) whether in case of sub-optimal viral suppression, an early add-on strategy is better in the long-term than a switch to a more potent drug with a high genetic barrier.
authors.affiliation: Service d'Hépato-gastroentérologie Hôpital Saint Joseph, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Kahloun
authors.forename: M
authors.initials: M
authors.lastname: Bourlière
authors.forename: F
authors.initials: F
authors.lastname: Zoulim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D009705:Nucleosides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D000077712:Telbivudine; D000068698:Tenofovir; D013936:Thymidine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D011744:Pyrimidinones; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine; C106812:adefovir dipivoxil; D013936:Thymidine