—Christine. M. Kukka, Project Manager, HBV Advocate
Jie Ma, Yingchun Zhang, Xinyue Chen, Yi Jin, Dexi Chen, Yun Wu, Jing Cui, Haitao Wang, Jia Liu, Ning Li, and Feng Gao,
John E. Tavis, Editor.
global team of
researchers suggest lamivudine (Epivir-HBV) never be used to
treat hepatitis B
patients because it almost always induces drug resistance, and
sets the stage
for resistance to other antivirals, such as entecavir
first antiviral approved for hepatitis B treatment, has fallen
out of favor in
North America and Europe because of its high drug resistance
rate. But because
of its low cost, it is still used here and as the primary
treatment in Asia and
other regions where the majority of hepatitis B patients live.
published in the July 30 isuse of PLoS One,
examined the molecular make-up of the hepatitis B virus (HBV)
in many patients
who had been treated with lamivudine as well as patients who
had never been
treated. They found the many patients who generally fail to
treatment carry the mutation that allows the virus to quickly
resistance to lamivudine.
strongly suggest that the use of lamivudine will not benefit
...patients," they wrote. "Firstly, the preexisting (lamivudine)
mutations can quickly lead to treatment failure due to drug
Secondly, the development of lamivudine mutations in all
patients who fail to
respond to treatment even if lamivudine is not used, ..."will
compromise the efficacy of lamivudine when used as a second-line
patients can quickly develop drug resistance to entecavir in the
of lamivudine mutations, the lamivudine mutations can
the efficacy of entecavir," they concluded.
that doctor screen patients for these mutations before
prescribing or changing treatment
"... to most effectively treat chronic hepatitis B patients by
only sensitive drugs."
Preexisting Drug-Resistance Mutations and Treatment Failure in
preexisting minority drug-resistance mutations in treatment
failure has not
been fully understood in chronic hepatitis B patients. To
of drug resistance, we analyzed drug-resistance mutations in 46
treatment-failure patients and in 29 treatment-naïve patients
linkage patterns of the drug-resistance mutations in individual
using a highly sensitive parallel allele-specific sequencing
Lamivudine resistance (LAMr) mutations were predominant in
patients, irrespective of the inclusion of LAM in the regimen.
The primary LAMr
mutations M204V and M204I were detected in 100% and 30% of the
treatment-failure patients, respectively. Two secondary LAMr
mutations (L180M and
V173L) were also found in most treatment-failure patients (87%
respectively). The linkages containing these three mutations
resistant viruses. Importantly, minority LAMr mutations present
in <2% of
the viral population were detected in 83% of the treatment-naïve
Moreover, the low-frequency same linked LAMr mutations
detected in 24% of the treatment-naïve patients.
the selection of preexisting minority linked LAMr mutations may
be an important
mechanism for the rapid development of LAM resistance, caution
use of LAM to treat drug-experienced and -naïve hepatitis B
underline the importance of the detection of minority single and
drug-resistance mutations before initiating antiviral therapy.
Labels: lamivudine (Epivir-HBV) drug resistance, lamivudine resistance, mutations