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Gastroenterology. 2014 Apr;146(4):980-8. doi: 10.1053/j.gastro.2013.12.028. Epub 2013 Dec 22.

Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B.

Author information

1
Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Scott.fung@uhn.on.ca.
2
University of British Columbia, Vancouver, British Columbia, Canada.
3
Clinic for Infectious Diseases, Medical University of Novi Sad, Serbia.
4
Medical University of Warsaw, Warsaw, Poland.
5
Clinic for Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade Medical Faculty, Belgrade, Serbia.
6
Thomas Jefferson University, Philadelphia, Pennsylvania.
7
Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey.
8
National Institute for Infectious Diseases, "Prof Dr Matei Bals," Bucharest, Romania.
9
Gilead Sciences, Inc, Foster City, California.
10
University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic.
11
Auckland City Hospital, Auckland, New Zealand.

Abstract

BACKGROUND & AIMS:

Tenofovir disoproxil fumarate (TDF) is active against lamivudine-resistant hepatitis B virus (HBV) infection, but data to support its clinical efficacy in this setting are limited.

METHODS:

In a prospective, double-blind, 96-week trial, patients were randomly assigned (1:1) to groups given TDF (300 mg, n = 141) or a combination of emtricitabine (FTC, 200 mg; n = 139) and TDF (300 mg, FTC/TDF). Patients were hepatitis B e antigen (HBeAg)-positive or HBeAg-negative, with levels of HBV DNA ≥3 log10 IU/mL and lamivudine resistance mutations (HBV polymerase or reverse transcriptase amino acid substitutions rtM204I/V ± rtL180M by INNO-LiPA Multi-DR v3; Innogenetics, Inc, Alpharetta, GA). The primary end point was proportion with HBV DNA <69 IU/mL (Roche COBAS Taqman assay; Roche Molecular Systems, Inc, Pleasanton, CA).

RESULTS:

Patient groups were well matched for demographic and disease characteristics, including region (60% from Europe), HBV genotype (45% genotype D), HBeAg status (47% HBeAg-positive), and duration of lamivudine treatment (mean, 3.8 years). At week 96 of treatment, 89.4% of patients in the TDF group and 86.3% in the FTC/TDF group had levels of HBV DNA <69 IU/mL (P = .43). HBeAg loss and seroconversion did not differ between groups; only 1 patient (0.7%) in the FTC/TDF group lost hepatitis B surface antigen. Treatment was well tolerated; confirmed renal events (creatinine increase of ≥0.5 mg/dL [>44 umol/L], creatinine clearance <50 mL/min, or level of PO4 <2 mg/dL [<0.65 mmol/L]) were generally mild and infrequent (<1%). Small reductions (<2%) in mean bone mineral density of hip and spine were detected by dual-energy x-ray absorptiometry in both groups. No TDF resistance developed through 96 weeks of treatment.

CONCLUSIONS:

TDF alone is safe and effective for treatment of patients with lamivudine-resistant, chronic HBV infection. Clinical Trials.gov No, NCT00737568.

KEYWORDS:

HBV DNA; Hepatitis B e Antigen; Renal Function; Viral Suppression

PMID:
24368224
DOI:
10.1053/j.gastro.2013.12.028
[Indexed for MEDLINE]

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