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 21–80), 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.
- antiviral therapy
- hepatitis B
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See Commentary, p 148
Funding Gilead Sciences (East Melbourne Victoria, Australia) donated tenofovir disoproxil fumarate and provided research support for this study.
Competing interests Associate Professor Simone Strasser: participates as Speaker, in Gilead sponsored and Supported clinical trials (tenofovir) and as a member of a Gilead advisory board (tenofovir); Associate Professor Amanda Nicoll: research support from Gilead Sciences in 2004 (not ongoing); Associate Professor Stuart Roberts: member of Gilead advisory board; Professor Stephen Locarnini: research support from Gilead Sciences and Bristol Myers Squibb; Professor Peter Angus: member of Gilead advisory board and research support (see Grant support, below).
Ethics approval This study was conducted with the approval of the Austin Health human research ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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