[Resistance in hepatitis B virus].
The development hepatitis B virus (HBV) polymerase inhibitors has revolutionised the treatment of chronic HBV infection. However, the emergence of resistance mutations can compromise their clinical efficacy and it is mandatory to know the mechanisms of these resistances, its clinical implications, strategies for prevention and how to deal with the rescue. Since HBV has a high degree of replication and a high error rate, during their life cycle it will produce a large number of punctual mutations in individuals with active replication. Due to the large size of the HBV genome, all the possible changes may occur daily and should be screened before starting any antiviral therapy. Therefore, in individuals infected with HBV there is a mixture of similar viruses that evolves over time (quasispecies), some of which are carriers of resistance mutations to antivirals, which explains why they can be selected quickly after exposure to drug. Of the five drugs approved in Europe for the treatment of hepatitis B, three of them (lamivudine, adefovir and entecavir) are likely to be affected directly by these mutations, as well as other active drugs, such as telbivudine, tenofovir and the emtricitabine. The characterization of the resistance mutations is helpful for the prevention and the optimization of antiviral therapies.
Sheldon
Julie
J
Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España. julies73@yahoo.co.uk
Sarmento E Castro
Rui
R
Soriano
Vicente
V
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015684:Gene Products, pol / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008958:Models, Molecular; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015684:Gene Products, pol; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine