title: Dynamics of lamivudine-resistant hepatitis B virus during adefovir monotherapy versus lamivudine plus adefovir combination therapy.
abstract: Adefovir dipivoxil has been used alone or together with lamivudine to suppress lamivudine-resistant hepatitis B virus (HBV). However, the dynamics of HBV populations under different selection pressures and their impact on treatment outcome are poorly understood. Pyrosequencing was applied to quantify longitudinally the evolution of wild type and lamivudine/adefovir-resistant HBV. Eight patients, with lamivudine-resistant HBV, were randomized to receive adefovir monotherapy or adefovir/lamivudine combination therapy for a median of 79 and 71 weeks, respectively. Pyrosequencing proved highly sensitive with a lower limit of quantitation of minor HBV populations of 2% irrespective of viraemia levels. Adefovir/lamivudine treatment resulted in greater viraemia reduction than adefovir monotherapy. During combination therapy, lamivudine-resistant HBV populations (codons 180 and 204) remained dominant (>90%) and no adefovir-resistance developed. During adefovir monotherapy, reversion to wild-type HBV was detected in two patients with one patient accumulating rapidly adefovir-resistant HBV along with increased viraemia. In conclusion, the dynamics of drug-resistant HBV strains vary under different selection pressures which have a significant impact on the success of rescue therapy, as well as for the selection of new mutations. The use of techniques such as Pyrosequencing provides an evidence-based approach for successful management of drug-resistant HBV.
authors.affiliation: Virus Reference Department, Centre for Infections, Health Protection Agency, London, United Kingdom. samreen.ijaz@hpa.org.uk
authors.forename: Samreen
authors.initials: S
authors.lastname: Ijaz
authors.forename: Catherine
authors.initials: C
authors.lastname: Arnold
authors.forename: Samir
authors.initials: S
authors.lastname: Dervisevic
authors.forename: Jana
authors.initials: J
authors.lastname: Mechurova
authors.forename: Nick
authors.initials: N
authors.lastname: Tatman
authors.forename: Richard S
authors.initials: RS
authors.lastname: Tedder
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C053001:adefovir; D000225:Adenine