Tenofovir (Viread), one of the leading
antiviral drugs for
hepatitis B treatment, produced no drug resistance in 585 patients
after six
years of treatment.
The report, published in the August issue of
Hepatology,
followed 347 hepatitis B "e" antigen-negative patients and 238
"e" antigen-positive patients who had been treated with the daily
antiviral pill for six years.
They examined the molecular make-up of the
hepatitis B virus
of 52 patients who still had detectable HBV DNA after nearly six
years of treatment to see if any of them had
developed viral mutations that could "resist" tenofovir's ability
to
block viral replication.
The researchers reported that failure to take
the antiviral
as prescribed and natural viral mutations were behind the
persistance of detectable viral
load in these patients. Those patients were either switched to a
combination of
tenofovir and emtricitabine
or began
taking tenofovir as prescribed. To date, all patients have
achieved
undetecatable viral load.
Abstract:No
detectable
resistance to tenofovir disoproxil fumarate after 6 years of
therapy in
patients with chronic hepatitis B.
Kitrinos
KM, Corsa
A, Liu
Y, Flaherty
J, Snow-Lampart
A, Marcellin
P, Borroto-Esoda
K, Miller
MD. Gilead Sciences, Inc., Foster City, CA, USA.
One
major challenge
in the treatment of chronic hepatitis B
is to
maintain long-term viral suppression without promoting the
selection of
drug-resistant mutations.
We analyzed data from 347 hepatitis
B e antigen-negative and 238 hepatitis
B e
antigen-positive patients receiving tenofovir disoproxil
fumarate (TDF) in an
open-label, long-term extension of two phase 3 studies. To date,
resistance
analyses have been completed for patients receiving up to 288
weeks (6 years)
of TDF.
Population sequencing of hepatitis
B virus
(HBV) polymerase/reverse transcriptase (pol/RT) was attempted
for all patients
at baseline, and any patient who remained viremic (HBV DNA ≥400
copies/mL [≥69
IU/mL]) at week 288 or at the end of treatment with TDF (n = 52)
or
emtricitabine (FTC)/TDF (n = 7). Phenotypic analyses were
performed in HepG2
cells using recombinant HBV containing patient pol/RT sequences.
Approximately
half of the patients on open-label treatment who qualified for
genotyping had
pol/RT sequence changes compared to baseline (23/52 [44%] on
TDF, 4/7 [57%] on
FTC/TDF). Most changes were at polymorphic sites and none were
associated with
TDF resistance. Virologic breakthrough occurred infrequently and
was associated
with nonadherence to study medication in the majority of cases
(12/16, 75%).
Per protocol, 57 patients (10%) were eligible to switch to
FTC/TDF; the
majority had HBV DNA <400 copies/mL at their last study visit
regardless of
whether they switched to FTC/TDF (n = 34) or maintained TDF
monotherapy (n =
17). No patient exhibited persistent viremia (HBV DNA never
<400 copies/mL)
after week 240.
Conclusion: TDF monotherapy maintains effective
suppression of
HBV DNA through 288 weeks of treatment with no evidence of TDF
resistance.
(Hepatology 2013;).