AASLD: Tenofovir (Viread) Keeps HBV in Check in Nucleoside-Experienced Patients

BOSTON, Nov. 6 -- For nucleoside- experienced hepatitis B patients, tenofovir (Viread), a nucleoside inhibitor, appears to be highly effective as monotherapy, found a multicenter study.Treatment with tenofovir resulted in potent reductions in HBV DNA in patients who had previously been exposed to lamivudine (Epivir) or adefovir (Hepsera), reported Florian van Bömmel, M.D., of Charity Hospital in Berlin, and colleagues.In addition, there were no cases of viral breakthrough in a retrospective follow-up study, suggesting that tenofovir has a favorable resistance profile, said Dr. van Bömmel at the American Association for the Study of Liver Diseases meeting here.
Action Points
Explain to interested patients that the hepatitis B virus may rapidly develop resistance to single-agent therapy with a nucleoside analog, requiring a switch to another agent.
This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
"We conclude that tenofovir is an effective and well-tolerated treatment option for HBV-monoinfected patients with prior treatment experience," he said.
Tenofovir, an acyclic nucleotide reverse transcriptase inhibitor, is approved for the treatment of HIV infections, and in clinical studies has shown activity in patients co-infected with HBV-HIV who harbor both wild-type and lamivudine-resistant virus.
The authors conducted a retrospective cohort analysis of tenofovir monotherapy in patients with HBV monoinfection treated in 15 centers in Germany and the Netherlands. To avoid selection bias, the authors collected data on all patients with HBV treated with tenofovir at the participating centers.
The primary study endpoint was the percentage of patients with HBV DNA levels below the lower limit of detection of the assay used -- fewer than 400 HBV copies/mL. Secondary endpoints were HBe antigen loss, seroconversions, normal ALT and creatinine, HBV resistance mutations, and safety and tolerability.
They included in the cohort only those patients with chronic monoinfection, baseline HBV greater than 105 copies at the start of tenofovir therapy, and follow-up of at least six months.
Out of an initial cohort of 153, they excluded 45 patients because of low HBV DNA levels, short follow-up, poor compliance, or resistance to adefovir, as there is some evidence of cross-resistance with tenofovir, Dr. van Bömmel said.
The final analysis included 108 patients treated with tenofovir for a median of 20 months (range six to 54). The mean patient age was 42, 84 were male, the mean weight was 75 kg, 21 patients had liver cirrhosis, 75 were E-antigen positive, and the mean HBV DNA level was 6.6 log10 copies per mL.
The patients had previously been treated with either lamivudine monotherapy, adefovir monotherapy, sequential lamivudine and adefovir or an add-on combination of the two drugs, entecavir at 1 mg a day for two months (one patient), and sequential lamivudine and entecavir (one patient).
When the authors looked at treatment efficacy as measured by mean HBV DNA levels, they found that the mean level declined by 3.6 log10 at six months, 4 log10 at six months, and 4.1 log10 over baseline at 12 months.
HBV DNA was undetectable (400 copies/ml) in 72% and 91% of the patients at week 24 and week 48. After month 19, all patients still in the study had achieved HBV DNA levels that were less than 400 copies/mL.
Patients who were HBeAg-negative achieved DNA levels below the lower limit significantly faster than HBeAg-positive patients.
The level of HBV at baseline also had an effect on the rapidity of viral response, with patients who had fewer than 107 copies at baseline reaching the primary endpoint significantly more rapidly than patients with a greater number of HBV DNA copies.
At month 12, the presence of cirrhosis had no effect on treatment efficacy, 75% of patients had normal ALT levels, and 80% had HB-antigen seroconversion.
"In the total follow-up of our study, we found that 21% of the patients had HB-antigen seroconversions after a mean period of 12 months, and 2.7% of patients had HB-antigen loss after a mean follow-up period of 17 months," said Dr. van Bömmel.
There were no significant adverse events associated with tenofovir therapy, except for one case of mild creatinine elevation (0.15 mg/mL). There were no cases of viral breakthrough, as defined by an increase of more than 1 log10 HBV DNA copies over nadir.
In a separate poster presentation, Dr. van Bömmel and colleagues looked at a subgroup of patients excluded from the study because of adefovir resistance mutations, whom they had originally thought might be resistant to tenofovir.
They found that "in contrast to our initial impression, with longer follow-up, tenofovir monotherapy shows significant activity against different patterns of adefovir-resistant HBV mutations. In particular, no patient developed a viral breakthrough."
The studies were supported by the German Network for Excellence, European Network Virgil, and Gilead Sciences. Dr. van Bömmel has received scientific funding from Gilead.
Primary source: American Association for the Study of Liver DiseasesSource reference: van Bömmel F, et al "First multicenter evaluation of the efficacy of tenofovir in nucleos(t)ide analog experienced patients with HBV monoinfection" AASLD Meeting 2007; Abstract 83 presented Nov. 5