Katyna Borroto-Esoda1, Michael D Miller, Sarah Arterburn. 1. Department of Clinical Virology, Gilead Sciences, Inc., 4 University Place, 4611 University Dr, Durham, NC 27707, USA. Katyna.Borroto-Esoda@gilead.com
Abstract
BACKGROUND/AIMS: The rtA181V and rtN236T mutations have been associated with resistance to adefovir dipivoxil (ADV). Recent reports have proposed other ADV resistance (ADV-R) mutations. The aims of this study were to confirm the role of rtA181V and rtN236T in clinical resistance to ADV and to screen for other potential ADV-R mutations. METHODS: Patients from ADV studies (n=998) were screened for viral breakthrough and/or insufficient HBV DNA suppression after at least 48 weeks of ADV therapy [virologic failure, VF]. McNemar's exact test was used to test for differences in the proportion of patients with switches from consensus amino acid (AA) at baseline to non-consensus AA at VF and vice versa. RESULTS: Data obtained from 172 paired HBV polymerase sequences demonstrated that only positions rt181 and rt236 had significantly more changes among patients with VF after adjusting for multiple comparisons (p<0.0005). When tested separately, the mutations rtA181V and rtN236T were statistically significant (p<0.0005); no other AA position was associated with VF. Patients who had HBV DNA breakthrough were more likely to develop ADV-R mutations than patients with insufficient HBV DNA suppression (36% vs. 5%). CONCLUSIONS: rtA181V and rtN236T were the only HBV polymerase mutations significantly associated with virologic failure to adefovir dipivoxil.
BACKGROUND/AIMS: The rtA181V and rtN236T mutations have been associated with resistance to adefovir dipivoxil (ADV). Recent reports have proposed other ADV resistance (ADV-R) mutations. The aims of this study were to confirm the role of rtA181V and rtN236T in clinical resistance to ADV and to screen for other potential ADV-R mutations. METHODS:Patients from ADV studies (n=998) were screened for viral breakthrough and/or insufficient HBV DNA suppression after at least 48 weeks of ADV therapy [virologic failure, VF]. McNemar's exact test was used to test for differences in the proportion of patients with switches from consensus amino acid (AA) at baseline to non-consensus AA at VF and vice versa. RESULTS: Data obtained from 172 paired HBV polymerase sequences demonstrated that only positions rt181 and rt236 had significantly more changes among patients with VF after adjusting for multiple comparisons (p<0.0005). When tested separately, the mutations rtA181V and rtN236T were statistically significant (p<0.0005); no other AA position was associated with VF. Patients who had HBV DNA breakthrough were more likely to develop ADV-R mutations than patients with insufficient HBV DNA suppression (36% vs. 5%). CONCLUSIONS: rtA181V and rtN236T were the only HBV polymerase mutations significantly associated with virologic failure to adefovir dipivoxil.
Authors: Eleftherios Michailidis; Karen A Kirby; Atsuko Hachiya; Wangdon Yoo; Sun Pyo Hong; Soo-Ok Kim; William R Folk; Stefan G Sarafianos Journal: Int J Biochem Cell Biol Date: 2012-04-16 Impact factor: 5.085