Bernd Moeller

Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients

BACKGROUND & AIMS Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy. METHODS Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾ 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾ 400 copies/ml (⩾ 69IU/ml) at or after week 24 could switch to open-label emtricitabine/tenofovir. RESULTS Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile. CONCLUSIONS Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.

536 EFFECTIVENESS OF TELBIVUDINE IN FIELD PRACTICE: A MULTICENTER GERMAN REAL-LIFE OBSERVATIONAL STUDY

blood samples revealed that the percentage of viruses with at least one of these stop codons ranged from 3% to 79%. In two cases even additional stop codons in the HBsAg reading frame were detected in clonal experiments. Different stop codons were located either in the same HBV genome or in distinguished virus populations. Of note, the polymerase mutation A181T did not always lead to a stop codon in the HBsAg, which for one case was disclosed by clonal experiments. Furthermore, clonal experiments showed that in the vast majority of HBV clones the polymerase mutations M204V and A181T were not located in the same genome. Conclusions: The overlapping reading frames of viral HBsAg and polymerase lead to the occurrence of mutations with complex mutational patterns. The exact and sensitive detection of truncated HBsAgs in HBV resistant isolates is limited by using population sequencing methods in routine HBV drug resistance assays.

Sa1052 Thyroid Dysfunction Triggered by Peginterferon Alfa-2B / Ribavirin Treatment of Chronic HCV Genotype 1 Infection Favors Sustained Virologic Response (SVR) by Reducing

A S L D A b st ra ct s International, Cambridge, MA). From the focus groups, there were 37 items (scale: 1= not important at all: 5 = extremely important) generated to assess dimensions believed to predict treatment satisfaction (TS). A separate and global measure of TS was developed using a tenpoint scale ranging from not satisfied at all to extremely satisfied. The 37 item instrument was pre-tested in 145 patients with a diagnosis of HCV (n =136 received past treatment; n=4 receiving current treatment for HCV) who were currently under the care of gastroenterologists and primary care physicians through Mayo Clinic, Rochester, MN. Subsequently, data collected through Harris Interactive, a web-based panel, were used to develop the confirmatory factor analysis (CFA) model. Structural equation modeling (SEM) was used to test the hypothesized relationships among three CFA dimensions and the global measure of TS. The panel included 333 patients with an HCV diagnosis (n=213 received past treatment; n=70 receiving current treatment for HCV). Results: Average age in the Harris Interactive panel was 51(SD = 12.1) years. Males comprised 55.0% of the sample and time since HCV diagnosis was approximately 12 (SD = 8.9) years. Principal components exploratory factor analysis (KMO = 0.97) reduced the 37-item domain to 12 items (Cronbach α = 0.95) explaining 75.0% of the variance. Cronbach α for three dimensions including Treatment Experience (TE), Side Effects (SE), and Social Aspects (SA) ranged from 0.70 to 0.90. Goodness of fit measures for the CFA measurement model (AMOS, Version 17) for 9 selected items were Chi squared = 20.9, df = 23, p = 0.59; CFI = 1.00, GFI = 0.99, TFI = 1.00, RMSEA = 0.001. All SEM estimates were significant (p < 0.05) as predictors of TE and TS and supported the relationship between the data and the hypothesized model. SE correlated positively with SA (0.85), SA was strongly and positively associated with TE (0.95). TE was positively associated with TS (0.12). Conclusion: The 10-item HCVTSAT demonstrated valid psychometric properties and was able to assess patient treatment satisfaction with HCV therapies.

309 COMPARISON OF EFFICACY BETWEEN PEGINTERFERON ALFA-2A OR −2B PLUS RIBAVIRINE IN THE TREATMENT OF CHRONIC HEPATITIS C PATIENTS IN DAILY ROUTINE: RESULTS FROM PRACTICE

309 COMPARISON OF EFFICACY BETWEEN PEGINTERFERON ALFA-2A OR −2B PLUS RIBAVIRINE IN THE TREATMENT OF CHRONIC HEPATITIS C PATIENTS IN DAILY ROUTINE: RESULTS FROM PRACTICE T. Witthoeft, S. Mauss, D. Hueppe, C. John, R. Heyne, B. Moeller, R. Link, A. Herrmann, A. Baumgarten, A. Dikopoulos, G. Teuber. Center of Gastroenterology, Stade, Center for HIV and Hepatogastroenterology, Duesseldorf, Center for Gastroenterology, Herne, Center of Gastroenterology, Practice of Internal Medicine, Center of Gastroenterology and Livercenter, Berlin, Internal Medicin, St. Josefs-Krankenhaus, Offenburg, Internal Medicine II, Friedrich-Schiller-Universitaet, Jena, Klinik fuer Innere Medizin I, Universitaetsklinikum Ulm, Ulm, Interdisziplinares Facharztzentrum Sachsenhausen, Frankfurt/Main, Germany E-mail: dr.thomas.witthoeft@t-online.de