title: Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders.
abstract: OBJECTIVE
  Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.
  
  
  METHODS
  We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).
  
  
  RESULTS
  All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.
  
  
  CONCLUSIONS
  Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.
authors.affiliation: Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA. byip.ucsd@gmail.com
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yip
authors.forename: Kevin
authors.initials: K
authors.lastname: Chaung
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Wong
authors.forename: Huy N
authors.initials: HN
authors.lastname: Trinh
authors.forename: Huy A
authors.initials: HA
authors.lastname: Nguyen
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
authors.forename: Ramsey
authors.initials: R
authors.lastname: Cheung
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine