No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection

Abstract

Tenofovir alafenamide (TAF) has shown equivalent efficacy and improved safety profiles for patients with chronic hepatitis B (CHB) compared to tenofovir disoproxil fumarate (TDF). However, limited data are available for its resistance profiles. In two clinical trials, 1,298 hepatitis E antigen-positive and -negative patients with CHB were randomized 2:1 and treated with TAF ( = 866) or TDF ( = 432). Baseline nucleos(t)ide analog resistance substitutions in HBV polymerase/reverse transcriptase (Pol/RT) were assessed using INNO-LiPA Multi-DR v2/v3. Resistance surveillance was conducted for patients with viremia (HBV DNA ≥ 69IU/ml) by HBV Pol/RT sequencing at week 96 or at discontinuation. phenotypic analysis was performed for patients with conserved site substitutions or virologic breakthrough while adherent to the study drug. At baseline, the majority of patients harbored virus with wild-type Pol/RT (89.2%), with 10.8% harboring resistance associated mutations. A similar percentage of patients in the TAF or TDF groups qualified for sequence analysis through week 96 (TAF, 11.1%; TDF, 10.9%). Of these, a small percentage of patients experienced virologic breakthrough (TAF, 2.8%; TDF, 3.2%) that was often associated with drug nonadherence (TAF, 30%; TDF, 50%). Across treatment groups, 132 patients qualified for sequence analysis through week 96, with nearly half having no sequence changes from baseline (43.2%). Most sequence changes occurred at polymorphic positions, and no isolates showed a reduction in susceptibility After 96 weeks, the proportion of patients achieving virus suppression (HBV DNA < 69 IU/ml) was similar across treatment groups, and no substitutions associated with resistance to TAF or TDF were detected. (These studies have been registered at ClinicalTrials.gov under identifiers NCT01940471 and NCT01940341.).

An Aging Population of Chronic Hepatitis B With Increasing Comorbidities: A Territory‐Wide Study From 2000 to 2017

“…(24) So far, no drug resistance has been identified in up to 96 weeks of TAF treatment. (25) Because of these new data, patients on TDF at risk of development and/or with underlying renal disease should be considered for a switch to entecavir or TAF, depending on previous lamivudine exposure. (8) Bone safety is also another concern in CHB, given that vitamin D deficiency is highly prevalent in Chinese CHB patients.…”

“…Fewer TAF recipients experienced a decline in estimated glomerular filtration rate (eGFR) >25% had a confirmed eGFR of <50 mL/min . So far, no drug resistance has been identified in up to 96 weeks of TAF treatment . Because of these new data, patients on TDF at risk of development and/or with underlying renal disease should be considered for a switch to entecavir or TAF, depending on previous lamivudine exposure…”

Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis

“…TAF, the more recently approved formulation of tenofovir, also appears to show a high barrier to the development of viral resistance. A recent randomized trial comparing TAF vs. TDF in 1298 CHB carriers demonstrated comparable rates of virological breakthrough with no identified HBV mutations associated with treatment resistance after 96 weeks of treatment [ 65 ]. However, two recent reports have identified TDF resistance mutations within the HBV genome.…”

The Strategy and Efficacy of Prophylaxis Against Hepatitis B Virus Recurrence After Liver Transplantation in the Era of High Potent Nucleos(t)ide Analogues: A Meta-Analysis

“…HP NAs (i.e. ETV, TDF, TAF) was an optimal choice for HBV prophylaxis due to superiority at e cacy and genetic barrier (65)(66)(67)(68). Currently there were only two studies adopting HP NAs monoprophylaxis to over 10 patients 47,53 .…”