Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B.

Author(s): Patterson SJ, George J, Strasser SI, Lee AU, Sievert W, Nicoll AJ, Desmond PV, Roberts SK, Locarnini S, Bowden S, Angus PW

Affiliation(s): Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia. scott.patterson@austin.org.au

Publication date & source: 2011-02, Gut., 60(2):247-54. Epub 2010 Oct 29.

Publication type: Clinical Trial; Multicenter Study; Research Support, Non-U.S. Gov't

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 >10 copies/ml if HBeAg positive, > 10 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 log 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 log 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 naive patients.