[18] Serial HBV DNA level measurements were systematically performed during therapy, as well as population sequencing of the full-length HBV reverse-transcriptase gene at baseline and, in patients with detectable serum HBV DNA, at weeks 48, 96, 144, 192, and 240. Resistance-associated substitutions were selected

in 29 patients during this website the 240-week study. Their viral dynamics classified them into three groups: responders (HBV DNA level reduction of more than 3 Log10 IU/mL) who experienced secondary treatment failure (reincrease in the HBV DNA level of more than 1 Log10 IU/mL above the nadir); suboptimal responders (HBV DNA level reduction of less than 3 Log10 IU/mL) who developed amino acid substitutions in a context of a slow, gradual reincrease in viral replication; Ferrostatin-1 order and responders who developed the amino acid substitutions without any virological breakthroughs. We selected the first 7 patients displaying these three dynamic patterns to study HBV population dynamics during adefovir exposure. The 7 patients were 5 men

and 2 women (26-59 years of age). Their characteristics, including serial reverse-transcriptase sequence analysis by means of cloning sequencing, have been described elsewhere.[11] Correspondence with the numbering in the previous article is shown in Supporting Table 1. None of them had previously received nucleoside/nucleotide analog treatment, and all received 10 mg/day of adefovir for the full study period. In four cases (patients 1, 2, 5, and 7), lamivudine was added during adefovir therapy because of virological

failure. Serial serum samples taken at baseline and during adefovir therapy were analyzed by UDPS. The data were then analyzed and interpreted with a specific software package. Two independent groups of patients were used as comparators for the frequency of amino acid substitutions associated with adefovir resistance at baseline. The first group included 5 check details treatment-naïve, HBeAg-positive patients (3 men and 2 women, 15-18 years of age) treated with 10 mg/day of adefovir (104 weeks in 3 cases, 196 weeks in 2 cases) who responded to therapy and achieved an HBe seroconversion with sustained undetectable HBV DNA after therapy. These patients were randomly selected from a larger group of patients included in a previously reported study reporting on the safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents with CHB who responded to this therapy.[19] The second group included 11 treatment-naïve patients with CHB (22-60 years of age) consecutively observed for the first time in the Department of Hepatology of the University Hospital of Caen, France, during the 2008-2011 period. Baseline samples were analyzed by UDPS, and the results were interpreted with the same software package.