title: Switching patients with lamivudine resistant chronic hepatitis B virus from tenofovir to adefovir results in less potent HBV-DNA suppression.
abstract: The nucleotide analogues, tenofovir disoproxil fumarate and adefovir dipivoxil, inhibit viral replication and are both effective against the hepatitis B virus (HBV). In our department, tenofovir was prescribed in addition to lamivudine for the treatment of lamivudine resistant chronic hepatitis B. After registration of adefovir, 10 patients were switched to adefovir monotherapy. We studied changes in HBV-DNA and alanine aminotransferase (ALT) in these patients. The median treatment duration with tenofovir was 78 weeks resulting in a median viral load reduction of 5.4 (range 6.8-2.3) log(10) copies/mL compared to baseline (P = 0.005). Two patients had an increase >1 log(10) copies/mL during tenofovir treatment. After the switch to adefovir, six out of 10 patients had an HBV-DNA >4 log(10) copies/mL and the median HBV-DNA increased from 2.8 to 4.5 log(10) copies/mL (P = 0.017). The factors associated with relapse were HBV-DNA PCR positivity at the time of switch and genotype B or D. ALT levels at the beginning of tenofovir treatment also might be a factor. Retreatment with tenofovir (n = 3) resulted in a rapid decline in HBV-DNA. Tenofovir is a potent antiviral drug. Switching to adefovir resulted in viral relapse in 60% of patients and retreatment with tenofovir resulted again in viral decline, which suggests that tenofovir is a more potent antiviral agent.
authors.affiliation: Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: W F
authors.initials: WF
authors.lastname: Leemans
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: H G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: R A
authors.initials: RA
authors.lastname: de Man
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D004279:DNA, Viral / Q000187:drug effects; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068698:Tenofovir; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine