Adefovir dipivoxil treatment of lamivudine-resistant chronic hepatitis B.

Abstract

Adefovir dipivoxil (ADV)-resistant mutations have been identified in treating hepatitis B virus (HBV) infection. This study aimed to analyze the response, the incidence of ADV resistance and the virologic characteristics of ADV therapy. A total of 29 CHB patients with confirmed lamivudine (LAM)-resistant HBV were treated with ADV for more than 52 weeks. Serum HBV DNA, HBV genotypes and sequences of HBV polymerase reverse-transcriptase domain were determined. Rates for the biochemical response, HBeAg loss, HBeAg seroconversion and virologic response (< 200 copies/mL of HBV DNA) were 82.8, 23.5, 11.8, and 48.3%, respectively, at week 52 of treatment. Lower pre-treatment mean HBV DNA level was the only significant factor associated with negative HBV DNA after ADV therapy. Six (20.7%) patients had clearance of LAM-resistant YMDD variants with replacement by the wild type HBV at week 52. The rtN236T, rtA181V/T and rtI233V were not identified before ADV therapy and the genotypic mutation of rtN236T was detected in one (3.4%) patient. In conclusion, the 52-week ADV treatment for patients with LAM-resistant HBV variants significantly achieved normalization of ALT levels, reduced serum HBV DNA levels and induced HBeAg loss and seroconversion. The emergence of ADV-resistant mutations seemed rare at weeks 52.

• Authors: Chia-Yen Dai, Wan-Long Chuang, Ming-Yen Hsieh, Li-Po Lee, Jee-Fu Huang, Nai-Jen Hou, Zu-Yau Lin, Shinn-Cherng Chen, Ming-Yuh Hsieh, Liang-Yen Wang, Jun-Fa Tsai, Wen-Yu Chang, Ming-Lung Yu
• Journal: Antiviral research (Antiviral Res) Vol. 75 Issue 2 Pg. 146-51 (Aug 2007) ISSN: 0166-3542 [Print] Netherlands
• PMID: 17400303 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antibodies, Viral
• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Organophosphonates
• Reverse Transcriptase Inhibitors
• Lamivudine
• Creatinine
• Alanine Transaminase
• Adenine
• Bilirubin
• adefovir dipivoxil

Topics

• Adenine (analogs & derivatives, pharmacology, therapeutic use)
• Adult
• Aged
• Alanine Transaminase (blood)
• Antibodies, Viral (blood)
• Antiviral Agents (therapeutic use)
• Bilirubin (blood)
• Creatinine (blood)
• DNA, Viral (blood, genetics)
• Drug Resistance, Viral (genetics)
• Female
• Genotype
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, genetics, immunology)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Humans
• Lamivudine (pharmacology, therapeutic use)
• Male
• Middle Aged
• Mutation
• Organophosphonates (pharmacology, therapeutic use)
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Time Factors
• Treatment Outcome
• Viral Load