title: Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.
abstract: OBJECTIVE
  To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S).
  
  
  METHODS
  Nucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR.
  
  
  RESULTS
  A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg(+) ) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36-0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55-0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments.
  
  
  CONCLUSIONS
  CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.
authors: Department of Gastroenterology, Koç University Hospital, Zeytinburnu, Istanbul, Turkey.
authors: Bulent
authors: B
authors: Baran
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Ozlem Mutluay
authors: OM
authors: Soyer
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Asli Cifcibasi
authors: AC
authors: Ormeci
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Suut
authors: S
authors: Gokturk
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Sami
authors: S
authors: Evirgen
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Filiz
authors: F
authors: Akyuz
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Cetin
authors: C
authors: Karaca
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Kadir
authors: K
authors: Demir
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Fatih
authors: F
authors: Besisik
authors: Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Derya
authors: D
authors: Onel
authors: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Mine
authors: M
authors: Gulluoglu
authors: Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Selim
authors: S
authors: Badur
authors: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
authors: Sabahattin
authors: S
authors: Kaymakoglu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D000068698:Tenofovir / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000068698:Tenofovir; D000410:Alanine Transaminase
keywords: adefovir failure; chronic hepatitis B; genotypic resistance; tenofovir disoproxil fumarate