Scott Fung1, Peter Kwan2, Milotka Fabri3, Andrzej Horban4, Mijomir Pelemis5, Hie-Won Hann6, Selim Gurel7, Florin A Caruntu8, John F Flaherty9, Benedetta Massetto9, Phillip Dinh9, Amoreena Corsa9, G Mani Subramanian9, John G McHutchison9, Petr Husa10, Edward Gane11. 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). HBeAgloss 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.
RCT Entities:
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.
Authors: Andrea L Cathcart; Henry Lik-Yuen Chan; Neeru Bhardwaj; Yang Liu; Patrick Marcellin; Calvin Q Pan; Maria Buti; Stephanie Cox; Bandita Parhy; Eric Zhou; Ross Martin; Silvia Chang; Lanjia Lin; John F Flaherty; Kathryn M Kitrinos; Anuj Gaggar; Namiki Izumi; Young-Suk Lim Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Vincent Soriano; Pablo Labarga; Carmen de Mendoza; José M Peña; José V Fernández-Montero; Laura Benítez; Isabella Esposito; Pablo Barreiro Journal: Curr HIV/AIDS Rep Date: 2015-09 Impact factor: 5.071