Week 48 Resistance Surveillance in Two Phase 3 Clinical Studies of Adefovir Dipivoxil for Chronic Hepatitis B

• DOI: 10.1053/jhep.2003.50288
• Publication Date: 2003-06-26T16:37:21Z
• Authors: Christopher E. We...; Huiling Yang; William E. Delaney; Craig S. Gibbs; Michael D. Miller; Michael Wulfsohn; John Fry; Carol L. Brosgart; Shelly Xiong
• Keywords: Adefovir; Hepatitis B

Seven hundred nucleoside treatment–naive patients were enrolled in two phase 3 trials of adefovir dipivoxil (ADV) for the treatment chronic hepatitis B. To monitor emergence potential resistance mutations over first 48 weeks, all intent–to–treat (467 ADV–treated and 228 placebo patients) included a prospectively defined, treatment–blinded, virology substudy. The study protocol mandated genotypic analysis with detectable B virus (HBV) DNA by Roche Amplicor polymerase chain reaction (PCR) at baseline week 48, vitro phenotypic analyses conserved site substitutions HBV or 1.0 log 10 greater increase from nadir. Paired sequences entire reverse transcriptase obtained 271 227 using sequencing method that detects down to 30% minor species present within mixtures. Four (rtS119A, rtH133L, rtV214A, rtH234Q) developed once each sites 4 patients. 6 mutants encoding emerged remained fully susceptible . Furthermore, these had HBV–DNA reductions 3.3 5.9 copies/mL no rebound. All other occurred very low frequencies (<1.6%) polymorphic not associated increases In conclusion, identified large group treated ADV weeks.