Reuters Health Information: Tenofovir monotherapy effective for entecavir-resistant HBV
Tenofovir monotherapy effective for entecavir-resistant HBV
Last Updated: 2015-05-13
By Lorraine L Janeczko
NEW YORK (Reuters Health) - For entecavir-resistant
hepatitis B virus (HBV) infection, tenofovir alone appears to be
as effective as a tenofovir/entecavir combination, new research
from Korea suggests.
"Our data suggest that TDF (tenofovir disoproxil fumarate)
monotherapy can be a safe and efficacious option for the
treatment of hepatitis B patients regardless of previous
exposure to other drugs or pre-existing resistance profile,"
wrote lead author Dr. Young-Suk Lim of the University of Ulsan
College of Medicine in Seoul, in an email to Reuters Health.
The 48-week randomized trial involved 90 HBV patients with
entecavir (ETV) resistance-associated mutations and serum HBV
DNA concentrations >60 IU/mL.
As reported online April 30 in Gut, everyone received 300
mg/day of TDF (Viread, Gilead Sciences, Inc.) and 45 also
received 1 mg/day of ETV (Baraclude, Bristol-Myers Squibb).
At week 48, the proportion of patients who reached the
primary efficacy endpoint of HBV DNA <15 IU/mL was similar with
TDF vs TDF+ETV (71% vs 73%). The mean change in HBV DNA levels
from baseline was also similar (3.66 vs 3.74 log10 IU/mL).
One patient on monotherapy had virological breakthrough,
which the authors attributed to poor drug adherence.
At week 48, six and three patients in the TDF and TDF+ETV
groups, respectively, maintained their baseline resistance
mutations (p>0.99) and none developed additional resistance
Safety profiles were similar in both groups, according to
"Even if HBV replication is completely suppressed, very few
patients achieve HBsAg (hepatitis B surface antigen)
seroclearance, which is the closest to a hepatitis B cure," Dr.
Lim wrote in an email. "So to prevent liver disease progression,
most patients require long-term nucleoside/nucleotide (NUC)."
Long-term combination therapy may also carry a higher risk
of adverse events and drug-drug interaction as well as higher
inconvenience and cost than monotherapy, he added.
"Many patients worldwide have developed drug resistance from
the widespread use of less potent NUCs, such as lamivudine (LAM)
or adefovir dipivoxil (ADV), which have a low genetic barrier to
resistance," he wrote.
"Most current practice guidelines recommend combination
therapy for patients with drug-resistant HBV. However, the
evidence level has been low," Dr. Lim wrote. "We think that our
study results provide a high level of evidence to change the
guidelines. In fact, World Health Organization and Asia-Pacific
guidelines are being revised to recommend TDF monotherapy for
patients with drug-resistant HBV."
Dr. Anna Lok of the University of Michigan Health System in
Ann Arbor, who was not involved in the study, wrote in an email,
"It was important to do this study because, if one drug is as
effective as two drugs, we can have major cost savings. Other
patients with entecavir-resistant HBV can be treated with
tenofovir monotherapy, greatly reducing cost."
The study will continue, Dr. Lim wrote. "The proportion of
patients with virologic response of TDF monotherapy and TDF+ETV
combination therapy was not satisfactory, about 65% after up to
96 weeks. Although none of the patients acquired emergence of
additional resistance HBV mutants, the results suggest that
long-term close observation is needed. Thus, the research will
be extended up to 240 weeks."
Gilead Sciences, Inc., which supplied the study drug, and
the Korean Health Technology Research and Development Project of
the Ministry of Health and Welfare supported the study.
Dr. Lim and one coauthor have financial relationships with
both Bristol-Myers Squibb and Gilead Sciences, as does Dr. Lok.