Tenofovir rescue regimen following prior suboptimal response to entecavir and adefovir combination therapy in chronic hepatitis B patients exposed to multiple treatment failures.

Abstract

In clinical practice, establishing a subsequent optimum treatment for chronic hepatitis B patients with a history of multiple NAs treatment failures, including a suboptimal response to a final therapy with combined ETV and ADV, is a complicated but crucial challenge. This study investigated the efficacy and safety of a tenofovir rescue regimen in these patients. A total of six eligible patients were enrolled and were switched to a tenofovir rescue regimen. At baseline, the genotypes and genotypic mutations of the reverse transcriptase and surface gene were determined by ultra-deep pyrosequencing, and further clonal analyses of the reverse transcriptase domain were performed to identify multidrug-resistant HBV strains. In addition, HBV DNA levels, serology, and biochemistry parameters were monitored at baseline and every 3 months, and abdominal ultrasonography was performed at baseline and every 6 months. All patients were confirmed to harbor LAM-related resistant HBV strains. After switching to the tenofovir rescue treatment, all patients had an undetectable level of HBV DNA within 6 months and achieved normalization of the ALT level within 9 months. These virological and biochemical responses persisted until the end of the observation period. None of the patients developed clinical deterioration or any adverse events related to the tenofovir therapy during the median 16.5-month follow-up. In conclusion, the tenofovir rescue regimen can be employed confidently as a highly effective and safe treatment choice following a suboptimal response to ETV plus ADV therapy for a subset of chronic hepatitis B patients with a history of multiple unsuccessful antiviral treatments.

• Authors: Qian Zhang, Tao Han, Cai-Yun Nie, Fu-Shuang Ha, Lei Liu, Hua Liu
• Journal: Journal of medical virology (J Med Virol) Vol. 87 Issue 6 Pg. 1013-21 (Jun 2015) ISSN: 1096-9071 [Electronic] United States
• PMID: 25716029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Organophosphonates
• Reverse Transcriptase Inhibitors
• Lamivudine
• entecavir
• Guanine
• adefovir
• Tenofovir
• RNA-Directed DNA Polymerase
• Adenine

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Aged
• Antiviral Agents (therapeutic use)
• DNA, Viral (blood)
• Drug Resistance, Viral (drug effects)
• Drug Therapy, Combination
• Female
• Genotype
• Guanine (analogs & derivatives, therapeutic use)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, genetics)
• Hepatitis B, Chronic (drug therapy, virology)
• High-Throughput Nucleotide Sequencing
• Humans
• Lamivudine (pharmacology, therapeutic use)
• Male
• Middle Aged
• Mutation
• Organophosphonates (therapeutic use)
• RNA-Directed DNA Polymerase (genetics)
• ROC Curve
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Tenofovir (pharmacology, therapeutic use)
• Treatment Failure
• Treatment Outcome