Failure to treat HBV with adefovir due to early selection of rtA181T mutation
Abstract number: P2013
Rodríguez-Domínguez M., Sanchez-Calvo J.M., Moreira V., Arranz G., Mateos M.L.
Introduction: The main goal of antiviral treatment against HBV is to abolish viral replication. Lamivudine is widely used but a high number of patients have no response to treatment due to the selection of HVB mutants, resistant to lamivudine during treatment. Therefore, adefovir-dipivoxil is the main alternative because it is less frequent to found resistant mutants of HBV. Recently we have had a patient with chronic HBV, HBeAg negative, in which treatment with adefovir get failed due to an early selection of a resistant mutant rt A181T.
Case report: A 47 years old female, asymptomatic, in a routine laboratory test was found to have a light increase in transaminases levels. Serological markers against hepatotropic viruses were studied founding a positive surface antigen for HBV (HBsAg) and a viral load (DNA-HBV) of 25×106 UI/mL, HBeAg was negative and anti-HBe was positive. No antibodies against HCV and HDV were found. Treatment with adefovir was started (10 mg/24 h). During a one year period, viral load decreased but always remaining about 89×104 UI/mL. A year and a half later viral load increased to 7.4×105 UI/mL. Suspecting a failure due to resistant HBV, adefovir was changed to tenofovir (300 mg/24 h). In a retrospective study of resistant mutations against lamivudine, adefovir, tenofovir and entecavir by a reverse-hybridation technique (INNO-Lipa DR v2 and v3, Innogenetics, Belgium) we found that the mutation rtA181T appears two months after the beginning of adefovir treatment. Also, we tested serum samples previous to adefovir treatment, and we did not found any other resistant mutation.
Discussion: rtA181T mutation is mainly associated with lamivudine resistant HBV from which susceptibility is reduced about three times. Against adefovir, this mutation can be considered secondary because it confers a low level of resistance in vitro. In our case, low levels of viral load were maintained during one year but never under 104 UI/mL. The retrospective study of banked serum samples allowed us to confirm that the treatment failure was due to the early selection of rtA181T mutant of HBV.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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