Document Detail

Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B.
MedLine Citation:
PMID:  21036792     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To determine the efficacy of tenofovir disoproxil fumarate (TDF) in adults with chronic hepatitis B virus (HBV) infection who had previously failed lamivudine (LAM) and had significant viral replication (HBV DNA >10⁵ copies/ml if HBeAg positive, > 10⁴ copies/ml if HBeAg negative) despite at least 24 weeks of treatment with adefovir dipivoxil (ADV).
DESIGN: A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM.
SETTING: Multiple tertiary referral centres.
METHODS: Sixty patients were enrolled. The median age was 48.5 years (range 21e80), 46 (77%) were male and 40 (67%) were HBeAg positive. Thirty-eight patients (63%) were switched from ADV to TDF, the remainder from ADV/LAM to TDF/LAM. At baseline, substitutions conferring resistance to LAM or ADV were present in 20 patients (33%) and 17 patients (28%), respectively. The median baseline viral load was 5.33 log₁₀ IU/ml (range 2.81-8.04). Patients initially treated with TDF monotherapy with persistent viral replication at or after 24 weeks were switched to TDF/LAM. The main outcome measures were change in HBV viral load from baseline and percentage of patients achieving an undetectable viral load (<15 IU/ml).
RESULTS: Results are reported at 96 weeks of treatment. One patient discontinued TDF at 10 days due to rash. The time-weighted change in viral load from baseline to week 12 was -2.19 log10 IU/ml overall. The median change in HBV DNA from baseline to weeks 12, 24, 48 and 96 was -2.86, -3.23, -3.75 and -4.03 log₁₀ IU/ml, respectively. At 48 and 96 weeks, 27/59 (46%) and 38/59 (64%) patients achieved a HBV DNA <15 IU/ml. The response was independent of baseline LAM therapy or mutations conferring ADV resistance.
CONCLUSIONS: In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naïve patients.
S J Patterson; J George; S I Strasser; A U Lee; W Sievert; A J Nicoll; P V Desmond; S K Roberts; S Locarnini; S Bowden; P W Angus
Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2010-10-29
Journal Detail:
Title:  Gut     Volume:  60     ISSN:  1468-3288     ISO Abbreviation:  Gut     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-05     Completed Date:  2011-02-03     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  247-54     Citation Subset:  AIM; IM    
Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia.
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MeSH Terms
Adenine / adverse effects,  analogs & derivatives*,  therapeutic use
Aged, 80 and over
DNA, Viral / blood
Drug Resistance, Viral / genetics
Epidemiologic Methods
Hepatitis B virus / drug effects,  genetics,  isolation & purification
Hepatitis B, Chronic / drug therapy*,  virology
Lamivudine / therapeutic use
Middle Aged
Organophosphonates / adverse effects,  therapeutic use*
Reverse Transcriptase Inhibitors / adverse effects,  therapeutic use*
Salvage Therapy / methods*
Treatment Failure
Treatment Outcome
Viral Load
Young Adult
Reg. No./Substance:
0/DNA, Viral; 0/Organophosphonates; 0/Reverse Transcriptase Inhibitors; 0/tenofovir disoproxil; 134678-17-4/Lamivudine; 6GQP90I798/adefovir; 73-24-5/Adenine
Comment In:
Gut. 2011 Feb;60(2):148-50   [PMID:  21205876 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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