By Arushi Sinha
SAN FRANCISCO -- November 7, 2008 -- Patients with hepatitis B virus (HBV) appear to have a high prevalence of lamivudine resistance genetic mutations that result in treatment failure, researchers reported here at the Liver Meeting 2008, the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
In these patients, treatment with adefovir or tenofovir proved more effective than treatment with lamivudine, said investigator Scott Fung, MD, Department of Medicine, University of Toronto, Toronto, Ontario.
The aim of this study was to examine the role of a patient's genetic profile in influencing the efficacy of treatment for HBV, he said in a presentation on November 2.
The goal was to document the incidence of antiviral resistance (AVR) mutations among a population of patients diagnosed with chronic HBV who had not received prior treatment. The researchers hypothesised that AVR mutations in a patient may prevent effective treatment with lamivudine and thus reduce clinical outcomes.
"We thought that there might be a low level of natural resistance," explained Dr. Fung.
The study enrolled 209 treatment-naïve patients aged a mean of 38 years with a mean HBV DNA of 5.7 +- 2.3 log10 IU/mL (male, 69%). Incidence of cirrhosis in the cohort was 15%.
The range of HBV genotypes was type A (8%), type B (32%), type C (47%), and type D (10%). Patients' AVR mutations were the following: rtL180M 10%; rtM204V/I, 12%; rtL80V/I, 9%; rtV173L, 3%; rtA181V/T, 0%; rtN236T, 0%.
Of these patients, 6 patients with genetic AVR mutations were treated with nucleoside therapy; 3 patients received lamivudine 100 mg daily for an average of 11 months, while 3 patients were treated with adefovir 10 mg daily or tenofovir 300 mg daily for an average of 7 months.
One of the patients treated with lamivudine exhibited a primary nonresponse, and 2 exhibited breakthrough infection. By contrast, all 3 patients treated with either adefovir or tenofovir demonstrated undetectable HBV DNA levels.
It was also found that those patients who were both male and exhibited a high viral load were at greater risk of having AVR mutations.
Results showed that 21 patients (10%) had lamivudine resistance at baseline.
Mutations resulting in a resistance pathway were fairly common, occurring in about 10% of patients. For those patients who did have the resistant mutation, treatments other than lamivudine, such as adefovir or tenofovir, proved more effective.
Overall, the findings suggested that creating a genetic profile for antiviral resistance is important and can influence therapeutic regimens.
"In this study, we probed over 200 treatment-naïve patients, and to our surprise we found that there is resistance to a commonly-used agent for the treatment of chronic hepatitis B," said Dr. Fung. "We should therefore be using agents that have no known resistance at baseline."
[Presentation title: Lamivudine-Resistant Mutation Among Treatment-Naïve Hepatitis B Patients Is Common and May Be Associated With Treatment Failure. Abstract 888]
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