SAN FRANCISCO, CA—Monotherapy with tenofovir disoproxil fumarate (TDF) was equally effective as combination therapy with emtricitabine/TDF (FTC/TDF) in patients with chronic hepatitis B virus (HBV) infection harboring lamivudine resistance mutations, a study presented at The Liver Meeting® 2015 has found.

Thomas Berg, MD, from University Hospital Leipzig, Leipzig, Germany, and colleagues also found no evidence of emergent TDF resistance, and the presence of entecavir resistance or prior exposure to adefovir or entecavir “had no impact on HBV DNA levels,” he noted.

Treatment of chronic HBV infection with lamivudine, a nucleoside analog, is associated with development of resistance in up to 70% of patients after 5 years, Dr. Berg noted. He and his team set out to compare amino acid changes within the HBV polymerase/reverse transcriptase (pol/RT) following up to 5 years (240 weeks) of treatment with TDF or the combination of FTC/TDF.

The prospective Phase 3b study enrolled 280 patients who were randomized 1:1 to receive TDF 300mg (n=141) or FTC/TDF (n=139) for up to 240 weeks.

“In addition to all patients having lamivudine exposure, 61 (22%) had prior or current adefovir exposure and 13 (5%) had entecavir exposure,” they reported.

Population sequencing at baseline identified pre-treatment drug resistance mutations that included lamivudine (n=253; 90%), adefovir (n=5; 2%), and entecavir (n=25; 9%).

Virologic breakthrough was defined as confirmed HBV DNA ≥69 IU/mL or ≥1-log10 increase from nadir. Baseline and annual population sequencing of HBV pol/RT were attempted for all patients, as well as at study discontinuation if HBV DNA ≥69 IU/mL.

Through Year 5, in both TDF and FTC/TDF treatment groups, 83% (n=117/141 and n=115/139, respectively) of patients had HBV DNA <69 IU/mL.

The TDF arm comprised 4 (3%) viremic patients at Year 5, with 1 patient experiencing virologic breakthrough, who discontinued at Week 24. Unique polymorphic changes were found in the virologic breakthrough patient; the remaining patients had no change or were unable to genotype. The FTC/TDF arm included 7 (5%) viremic patients at Year 5, with no patients experiencing virologic breakthrough. Among these, 3 had conserved site changes (2 were non-adherent to study medication); 1, a polymorphic site change; and 3, no change. 

Of the 11 patients who qualified for testing, 7 (64%) were non-adherent to study medication at the time of qualification, the study authors pointed out. Of the 7 patients, 4 with detectable tenofovir in plasma had low-level HBV DNA (<2.6-log10 IU/mL) at the time of testing.