title: Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients.
abstract: OBJECTIVE
  To assess the efficacy of tenofovir disoproxil fumarate (TDF) in lamivudine (LAM)-resistant patients with a suboptimal response to LAM plus adefovir (ADV).
  
  
  METHODS
  We retrospectively analyzed the efficacy of switching to tenofovir disoproxil fumarate in suboptimal responders to lamivudine plus adefovir. Charts were reviewed for LAM-resistant chronic hepatitis B (CHB) patients who visited the Zhejiang Province People's Hospital and The First Affiliated Hospital, College of Medicine, Zhejiang University, from June 2009 to May 2013. Patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM plus ADV combination therapy were included. Patients with a suboptimal response to LAM plus ADV were randomized to switch to TDF monotherapy (300 mg/d orally; TDF group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally; LAM plus ADV group) and were followed for 48 wk. Serum HBV DNA was determined at baseline and weeks 4, 12, 24, 36, and 48. HBV serological markers and biochemistry were assessed at baseline and weeks 12, 24, and 48. Resistance surveillance and side effects were monitored during therapy.
  
  
  RESULTS
  Fifty-nine patient were randomized to switch to TDF (n = 28) or continuation with LAM plus ADV (n = 31). No significant differences were found between the groups at baseline. Prior to TDF therapy, all patients had been exposed to LAM plus ADV for a median of 11 mo (range: 6-24 mo). No difference was seen in baseline serum HBV DNA between the two groups [5.13 ± 1.08 log10 copies/mL (TDF) vs 5.04 ± 31.16 log10 copies/mL (LAM + ADV), P = 0.639]. There was no significant difference in the rates of achieving complete virological response (CVR) at week 4 between the TDF and LAM + ADV groups (17.86% vs 6.45%, P = 0.24). The rate of achieving CVR in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12, 82.14% vs 22.58% at week 24, 89.29% vs 25.81% at week 36, and 96.43% vs 29.03% at week 48, respectively (P < 0.001). The rate of alanine aminotransferase normalization was significantly higher in the TDF than in the LAM plus ADV group at week 12 (75% vs 17.86%, P < 0.001), but not at week 24 (78.57% vs 54.84%, P = 0.097) or 48 (89.26% vs 67.74%, P = 0.062). Patients were hepatitis B e antigen (HBeAg) positive at baseline. There was no significant difference in HBeAg negativity between the TDF and LAM plus ADV groups at week 48 (4% vs 0%, P = 0.481). There were no drug-related adverse effects at week 48 in either group.
  
  
  CONCLUSIONS
  Switching to TDF monotherapy was superior to continuous add-on therapy in patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Dan-Hong
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Yuan-Jun
authors.initials: YJ
authors.lastname: Xie
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Nian-Feng
authors.initials: NF
authors.lastname: Zhao
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Pan
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Li
authors.affiliation: Dan-Hong Yang, Hong-Ying Pan, Hai-Jun Huang, Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Huang
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D010757:Phosphorous Acids / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D063065:Organophosphonates; D010757:Phosphorous Acids; D019259:Lamivudine; C053001:adefovir; D000225:Adenine
keywords: Adefovir; Hepatitis B virus; Lamivudine; Tenofovir disoproxil fumarate; Viral resistance