Tenofovir monotherapy effective for adefovir-resistant chronic hepatitis B

Reuters Health Information: Tenofovir monotherapy effective for adefovir-resistant chronic hepatitis B

Tenofovir monotherapy effective for adefovir-resistant chronic hepatitis B

Last Updated: 2015-04-02

By Will Boggs MD

NEW YORK (Reuters Health) - Tenofovir disoproxil fumarate (TDF) monotherapy appears as effective as tenofovir-entecavir combination therapy for treating patients with adefovir-resistant chronic hepatitis B that has failed multiple drug treatments, researchers from Korea report.

"The cure of chronic hepatitis B (HBV) is very rarely achievable, and thus, long-term, almost indefinite nucleoside/nucleotide (NUC) treatment is required for the majority of patients," Dr. Young-Suk Lim, from the University of Ulsan College of Medicine, Seoul, told Reuters Health by email.

"Therefore, tenofovir monotherapy would be a reasonable option for the treatment of any drug-resistant patients, considering a comparable antiviral efficacy, extremely low risk of TDF-resistance, and lower cost compared with the most potent combination therapy (TDF+ entecavir (ETV)," Dr. Lim said.

Although combination therapy with a nucleoside analogue and a nucleotide analogue is recommended for patients with drug-resistant HBV, several recent studies suggested that TDF (Viread, Gilead Sciences) monotherapy is efficacious in many of these patients.

Dr. Lim's team compared efficacy of TDF monotherapy with that of TDF+ETV combination therapy in a randomized trial of 102 patients who had persistent HBV viremia with documented genotypic resistance to adefovir.

Virological responses at week 48 did not differ between the treatment groups, according to the March 23 Gut online report.

At week 48, 62% of TDF patients had HBV DNA levels below 15 IU/mL, compared with 63.5% of TDF+ETV patients. At week 96, 64% of TDF patients and 63.5% of TDF+ETV patients had HBV DNA levels below 15 IU/mL. The differences did not reach statistical significance.

The virological response rate was relatively flat beyond week 24, and prolongation of TDF therapy did not significantly increase the rate.

Higher baseline HBV DNA levels and harboring double adefovir-resistance mutations were associated with lower rates of virological response at 48 weeks.

Safety profiles were similar for the two treatment groups, and there were two cases of virological breakthrough (one in each group), both associated with decreased adherence to study medication.

"Not all of our patients have achieved virologic response during up to 96 weeks of treatment with TDF," Dr. Lim said. "Because the combination of TDF+ETV does not seem to further increase the rate of virologic response, our findings indicate that a more potent antiviral agent may be required for patients with HBV mutants resistant to multiple drugs."

In the meantime, Dr. Lim said, "we believe that tenofovir disoproxil fumarate (TDF) monotherapy is a safe and efficacious treatment for chronic hepatitis B patients regardless of the drug-resistance profile."

Gilead Sciences supported this study and supplied the study drug; the Korean Health Technology R & D Project also supported the study. Dr. Lim reported being an advisory board member for Bayer Healthcare, Bristol-Myers Squibb, and Gilead Sciences and receiving research support from them and Novartis; no other authors reported any disclosures.

SOURCE: http://bmj.co/1DzI4kO

Gut 2015.

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