Original articlePancreas, biliary tract, and liverNo Resistance to Tenofovir Disoproxil Fumarate Through 96 Weeks of Treatment in Patients With Lamivudine-Resistant Chronic Hepatitis B
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Patient Population and Study Design
The study design was previously described.23 Patients were randomized 1:1 to receive TDF or FTC/TDF for up to 240 weeks; results through week 96 are reported here. Serum and plasma samples were collected for genotypic, phenotypic, and plasma tenofovir level analyses. All authors had access to the study data and reviewed and approved the final manuscript. The study was conducted in compliance with all regulatory obligations and the institutional review board and informed consent regulations at
Pretreatment Resistance Analysis
Two hundred eighty patients were enrolled in the study, 141 in the TDF arm and 139 in the FTC/TDF arm. Patient characteristics were similar between arms except for the distribution of patients with previous ADV exposure. Of the 22% of patients previously treated with ADV, a significantly higher percentage were randomized to the FTC/TDF arm (28% vs 16% in the TDF arm, P = .012). All patients were assessed at screening for LAM-R by INNO-LiPA Multi-DR v3. Ninety-nine percent of patients (278 of
Discussion
The CHB patient population harboring resistance mutations to 1 or more nucleos(t)ide analogs, especially LAM, continues to increase and remains a major clinical challenge.2, 26 In this randomized, controlled study, TDF was shown to be effective in LAM-R patients for up to 96 weeks without evidence of TDF resistance. No additional benefit was observed with the addition of FTC vs TDF monotherapy. In the present analyses, virologic breakthrough was rare and associated with nonadherence to study
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2022, Journal of Clinical VirologyCitation Excerpt :He had previously achieved complete viral suppression on TDF. Pre-existing resistance to lamivudine is known to be associated with resistance to entecavir but not to tenofovir [8,17], yet the entecavir treatment seemed to allow for putative resistance development by releasing suppression of viral replication enough for new mutations to arise. Entecavir dosing was reduced, because of progressive kidney disease, subsequently viremia spiked, and new mutations developed.
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2017, Antiviral ResearchCitation Excerpt :One reason for this difference in response may be that all NRTIs target the YMDD active site of the pol/RT region, which is conserved across all genotypes (Bartholomeusz et al., 2004). Our data have demonstrated that all LAM-R and ETV-R isolates are sensitive to TAF, which is similar to what has been observed for TDF in vivo (Corsa et al., 2014) and TFV in vitro (Yang et al., 2005). These results are expected as TAF/TDF are acyclic phosphonates, while LAM and ETV are L-nucleosides and D-cyclopentanes, respectively, which have different paths to resistance development (Tenney, 2010).
Conflicts of interest The authors declare the following: Scott K. Fung and Edward Gane have received speaker honorariums and research grants from Gilead Sciences, Inc. Amoreena C. Corsa, Yang Liu, Ben Mitchell, Michael D. Miller, John F. Flaherty, and Kathryn M. Kitrinos were employed and own stock in Gilead Sciences, Inc.
Funding Supported financially by Gilead Sciences, Inc.