Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11146
Title: Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B.
Authors: Patterson, S J;George, J;Strasser, S I;Lee, A U;Sievert, W;Nicoll, A J;Desmond, Patricia M;Roberts, S K;Locarnini, S;Bowden, S;Angus, Peter W
Affiliation: Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia. scott.patterson@austin.org.au
Issue Date: 29-Oct-2010
Citation: Gut 2010; 60(2): 247-54
Abstract: 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).A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM.Multiple tertiary referral centres.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 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.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.
Internal ID Number: 21036792
URI: http://ahro.austin.org.au/austinjspui/handle/1/11146
DOI: 10.1136/gut.2010.223206
URL: http://www.ncbi.nlm.nih.gov/pubmed/21036792
Type: Journal Article
Subjects: Adenine.adverse effects.analogs & derivatives.therapeutic use
Adult
Aged
Aged, 80 and over
DNA, Viral.blood
Drug Resistance, Viral.genetics
Epidemiologic Methods
Female
Hepatitis B virus.drug effects.genetics.isolation & purification
Hepatitis B, Chronic.drug therapy.virology
Humans
Lamivudine.therapeutic use
Male
Middle Aged
Mutation
Organophosphonates.adverse effects.therapeutic use
Reverse Transcriptase Inhibitors.adverse effects.therapeutic use
Salvage Therapy.methods
Treatment Failure
Treatment Outcome
Viral Load
Young Adult
Appears in Collections:Journal articles

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