| Correlation Between Genotype and Antiviral Response to Emtricitabine 200 mg Once Daily Among HBeAg Negative Chronic HBV Patients
The purpose of this study was to evaluate the interaction of genotypic variations at Baseline (BL) and antiviral response among HBeAg negative (HBeAg -) patients with chronic hepatitis B virus (CHB) receiving emtricitabine (Emtriva, FTC) 200 mg QD.
Patients were enrolled in one of two double-blind, randomized 48-week studies. Serum HBV DNA levels were assessed by Digene Hybrid Capture II; lower limit of detection (LOD) of 4700 copies/mL [cp/mL]. Sequence analysis of the HBV POL and HBsAg reading frames was performed by di-deoxy sequencing.
Results
Two hundred patients were randomized to receive FTC 200 mg QD for 48 weeks [B102; 33 (21 na飗e, 12 experienced from FTCB 101), B301; 167 na飗e]. One hundred ninety one patients were evaluable for virologic and biochemical responses and for the emergence of drug resistance mutations based on BL genotype.
Thirty-six percent (36%, 68/191) were HBeAg- and phylogenetic analysis at BL revealed that 4, 28, 7 and 29 harbored HBV of genotype A, B, C and D, respectively. At 1 year, improvement in liver histology, i.e., reduction of at least 2 points in the Knodell necroinflammatory score and lack of fibrosis progression was observed in 75% (A), 68% (B), 60% (C) and 75% (D) of HBeAg- patients (missing=excluded).
Median log10 decreases in HBV VL at 1 year were -2.79, -2.14, -2.60 and -2.85 cp/mL and proportion of patients with undetectable VL was observed in 50%, 84.6%, 85.7% and 92.9% of patients with genotype A, B, C and D virus, respectively.
Median changes in ALT values were -134, -35, -38 and -53.5 IU/L at 1 year across genotypes A-D, respectively.
Resistance surveillance for patients with detectable viremia at 1 year revealed that 1/4 and 2/26 of the patients with genotype A and B, respectively harbored HBV DNA with mutations associated with resistance (rt204I/V+/-rt180M+/-rt173L).
There were no statistically significant differences between genotypes in any of the markers of response evaluated (p>0.05).
Conclusions
The authors conclude, 揂ntiviral response among HBeAg negative patients with CHB receiving FTC 200 mg QD for 1 year was not significantly different based on HBV genotype at Baseline.?
揙verall, FTC 200 mg QD produced potent viral suppression, demonstrated a low incidence of resistance mutations and ultimately resulted in improvement in liver histology in approximately 71% of these HBeAg- patients.?/span>
11/08/04 Reference
A Snow and others. CORRELATION BETWEEN BASELINE GENOTYPE AND ANTIVIRAL RESPONSE TO EMTRICITABINE 200 MG QD AMONG HBEAG NEGATIVE PATIENTS WITH CHRONIC HEPATITIS B INFECTION. Abstract 1133. 55th AASLD. October 29-November 2, 2004. Boston, MA. | 
发表于 2004-11-9 03:18
