Entecavir (Baraclude) and Tenofovir (Viread) Be First-line Treatment for Chronic
the annual Digestive Disease Week (DDW 2009) meeting
this week in Chicago, a panel of experts discussed the prevention and management
of antiviral drug resistance in patients receiving long-term treatment for chronic
hepatitis B virus (HBV) infection, according to DDW Daily News, the official
Lok, MD, MSc, MPH
clinical symposium entitled "Avoiding HBV Drug Resistance: How Many Drugs?"
featured a panel consisting of moderator George Lau, MD, from the University of
Hong Kong; Anna Lok, MD, MSc, MPH, from the University of Michigan Health System
in Ann Arbor; Daryl Lau, MD, from Beth Israel Deaconess Medical Center and Harvard
Medical School in Boston; and Marc Ghany, MD, from the Liver Diseases Branch of
the National Institute of Diabetes and Digestive and Kidney Diseases, part of
the National Institutes of Health.
more potent nucleoside analogs have demonstrated much lower rates of antiviral
resistance than older agents such as lamivudine
(Epivir-HBV), according to the panel members. Speaking during the discussion,
Dr. Ghany said, "The panel consensus is entecavir
(Baraclude) and tenofovir (Viread)
should be first-line [treatment]."
incidence of viral resistance to lamivudine -- the former standard of care --
rises from 24% after 1 year of treatment to 67% in year 4, reported Dr. Daryl
Lau. "It is no longer best for long-term therapy of chronic HBV," he
factors contribute to development of resistance, said Dr. Lok. These include viral
factors, such as the rate of HBV replication and the number of pre-existing viral
mutations; the drug's potency and genetic barriers to resistance; and factors
relating to the host, such as prior treatment, adherence, pharmacogenetics, and
body size. Adverse consequences of drug resistance include hepatitis flares and
hepatic decompensation due to ongoing viral replication.
frequency of viral resistance depends on the patient population, definitions of
drug resistance, and measurement techniques. Dr. Lok defined viral resistance
-- characterized by virological breakthrough -- as an increase in serum HBV DNA
of greater than or equal to 1 log above the nadir (lowest-ever) level or reappearance
of detectable HBV DNA.
of Viral Resistance
GLOBE Trial showed that a high HBV DNA level at week 24 of treatment predicts
viral resistance, Dr. Ghany said, "The take-home message is: if your patient
has a high viral load at week 24, you better do something, because these patients
have a high risk of developing resistance."
Ghany recommended changing therapy if treatment response is suboptimal, and listed
other ways to prevent viral resistance include avoiding inappropriate antiviral
treatment, using a potent agent that has a high genetic barrier to resistance,
reinforcing patient adherence, and starting treatment with a combination regimen.
prevent multidrug resistance, he suggested avoiding sequential monotherapy --
adding a single new drug after the previous one fails -- and choosing agents that
do not share a cross-resistance profile. For instance, a patient with viral resistant
to lamivudine is less likely to respond to telbivudine
Still Out on Combination Therapy for Hepatitis B
George Lau also spoke about combination therapy for chronic hepatitis B. The rationale
for combination therapy, he noted, is to enhance viral potency and increase the
genetic barrier to resistance.
are conflicting results in the medical literature on differences in HBV DNA suppression
between monotherapy and combination therapy. Some randomized clinical trials found
that antiviral efficacy is enhanced with the use of combination regimens.
first virologic breakthrough should be managed with combination therapy, not by
switching to another [single-agent] treatment," he said.
exception, he added, is lamivudine
plus adefovir (Hepsera), since
a study last year showed no greater antiviral effect with the combination versus
considering combination therapy, a clinician must weigh the potential benefits
against the drawbacks, including potentially higher treatment costs, more difficult
adherence, and additive side effects that include an increased risk of peripheral
neuropathy with telbivudine
and pegylated interferon (Pegasys).
that may especially benefit from combination therapy, he concluded, include those
with liver cirrhosis, HIV-HBV coinfection, suboptimal response to an initial drug,
and established resistance to antiviral medications.
Lok and Daryl Lau remarked that because extensive data are only available for
the older nucleoside analogs, more research using the newer drugs is needed to
determine the benefits of combination therapy.
B antiviral drug resistance common but avoidable. DDW Daily News. Digestive
Disease Week (DDW 2009). June 2, 2009.