Ug-resistant HBV results in breakthrough viremia leading to hepatitis and liver

Ug-resistant HBV results in breakthrough viremia leading to hepatitis and liver disease progression. To ensure good long-term outcomes, the conservation of HBV DNA suppression is essential. Early virologic response, particularly at Week 24, is 22948146 Eledoisin associated with better long-term POR-8 supplier outcomes in chronic HBV, while detectable HBV DNA at Week 24 is associated with a higher incidence of ontherapy drug resistance [14,15]. This predictive association has lead an international group of experts to propose the so-called “Roadmap” concept ?a therapeutic algorithm for the conditional intensification of nucleoside monotherapy based on early virologic response [16]. In the Roadmap, monotherapy is continued if plasma virus is undetectable (HBV DNA ,300 copies/mL) at Week 24; while for those 23977191 with detectable HBV DNA defined options exist for either intensification or continued monotherapy. The Roadmap principle is widely accepted in clinical practice [17], but has yet to be prospectively evaluated. In this study, we sought to confirm prospectively the clinical utility of the Roadmap by investigating whether the conditional intensification of telbivudine monotherapy with tenofovir, when indicated by the algorithm, results in effective virologic suppression in nucleosidenaive, HBeAg-positive patients with chronic hepatitis B. We present 52-week primary efficacy and safety data.Ethics StatementWritten informed consent was obtained and eligibility assessed at a screening visit up to 6 weeks before the first dose of telbivudine. The study was approved by the institutional review boards/independent ethics committees of each study center and was conducted in compliance with the principles of the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines and local regulatory requirements.PatientsThis study (ClinicalTrials.gov ID NCT00651209) had a multinational, single-arm, open-label design. Male and female adults ( 18 years) were recruited between April 2008 and September 2009 from 17 clinical centers in Argentina (n = 3), Brazil (4), China [Hong Kong] (2), Germany (4) and Thailand (4). Major inclusion criteria were: documented chronic hepatitis B with detectable HBsAg at screening and for at least 6 months prior; HBeAg-positive (HBeAg+) and HBeAb-negative at screening; serum HBV DNA 5 log10 copies/mL by COBAS Amplicor HBV MonitorH assay (Roche Molecular Systems Inc., Pleasanton, California); screening alanine aminotransferase (ALT) between 1.36 and 106 the upper limit of normal (ULN) with evidence of chronic liver inflammation ( 2 elevated ALT or aspartate aminotransferase values over at least 6 months). Exclusion criteria included: co-infection with hepatitis C virus, hepatitis D virus or HIV; hepatic decompensation; any prior nucleoside treatment or interferon/immunomodulator treatment in the 6 months before screening, or chronic renal insufficiency or serum creatinine clearance below 50 mL/min.Study DesignPatient disposition is shown in Figure 1 and the study design in Figure 2. Total treatment period is 104 weeks with the primary analysis at 52 weeks. Planned study visits occurred at Weeks 2, 4, 8, 12, 16, 24, 26, 30, 40, 48, and 52. All patients received oral telbivudine (600 mg once daily) for the first 24 weeks. At Week 26, patients with detectable HBV DNA at Week 24 ( 300 copies/mL by COBAS Amplicor) received tenofovir disoproxil fumarate (300 mg once daily) in addition to telbivudine t.Ug-resistant HBV results in breakthrough viremia leading to hepatitis and liver disease progression. To ensure good long-term outcomes, the conservation of HBV DNA suppression is essential. Early virologic response, particularly at Week 24, is 22948146 associated with better long-term outcomes in chronic HBV, while detectable HBV DNA at Week 24 is associated with a higher incidence of ontherapy drug resistance [14,15]. This predictive association has lead an international group of experts to propose the so-called “Roadmap” concept ?a therapeutic algorithm for the conditional intensification of nucleoside monotherapy based on early virologic response [16]. In the Roadmap, monotherapy is continued if plasma virus is undetectable (HBV DNA ,300 copies/mL) at Week 24; while for those 23977191 with detectable HBV DNA defined options exist for either intensification or continued monotherapy. The Roadmap principle is widely accepted in clinical practice [17], but has yet to be prospectively evaluated. In this study, we sought to confirm prospectively the clinical utility of the Roadmap by investigating whether the conditional intensification of telbivudine monotherapy with tenofovir, when indicated by the algorithm, results in effective virologic suppression in nucleosidenaive, HBeAg-positive patients with chronic hepatitis B. We present 52-week primary efficacy and safety data.Ethics StatementWritten informed consent was obtained and eligibility assessed at a screening visit up to 6 weeks before the first dose of telbivudine. The study was approved by the institutional review boards/independent ethics committees of each study center and was conducted in compliance with the principles of the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines and local regulatory requirements.PatientsThis study (ClinicalTrials.gov ID NCT00651209) had a multinational, single-arm, open-label design. Male and female adults ( 18 years) were recruited between April 2008 and September 2009 from 17 clinical centers in Argentina (n = 3), Brazil (4), China [Hong Kong] (2), Germany (4) and Thailand (4). Major inclusion criteria were: documented chronic hepatitis B with detectable HBsAg at screening and for at least 6 months prior; HBeAg-positive (HBeAg+) and HBeAb-negative at screening; serum HBV DNA 5 log10 copies/mL by COBAS Amplicor HBV MonitorH assay (Roche Molecular Systems Inc., Pleasanton, California); screening alanine aminotransferase (ALT) between 1.36 and 106 the upper limit of normal (ULN) with evidence of chronic liver inflammation ( 2 elevated ALT or aspartate aminotransferase values over at least 6 months). Exclusion criteria included: co-infection with hepatitis C virus, hepatitis D virus or HIV; hepatic decompensation; any prior nucleoside treatment or interferon/immunomodulator treatment in the 6 months before screening, or chronic renal insufficiency or serum creatinine clearance below 50 mL/min.Study DesignPatient disposition is shown in Figure 1 and the study design in Figure 2. Total treatment period is 104 weeks with the primary analysis at 52 weeks. Planned study visits occurred at Weeks 2, 4, 8, 12, 16, 24, 26, 30, 40, 48, and 52. All patients received oral telbivudine (600 mg once daily) for the first 24 weeks. At Week 26, patients with detectable HBV DNA at Week 24 ( 300 copies/mL by COBAS Amplicor) received tenofovir disoproxil fumarate (300 mg once daily) in addition to telbivudine t.

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