Page 74 - The Flying Publisher Guide to Hepatitis C Treatment

74 | Hepatitis C Treatment

The majority of DAAs have a low genetic barrier to resistance,
with the possible exception of nucleoside analogs inhibitors of
HCV polymerase.
There is broad cross resistance between drugs in the same
class, as has been shown for the two approved PIs, telaprevir and
boceprevir. Possible exceptions are the non-nucleoside
inhibitors of HCV polymerase that might be administered in
additive or synergistic combinations. The majority of patients
with virologic breakthrough during triple therapy with PIs
presented high-level resistant variants, these emerged more
frequently in the HCV genotype 1a patients (Kuntzen 2008);
predominant mutations were V36M and R155K compared to
A156T in genotype 1b. There is no information regarding the
possible archiving of drug resistant mutants in cellular
sanctuaries, as is the case for HIV. Emergence of resistance may
be limited by optimized pharmacokinetics of the DAAs and by
their use in combinations.

What does the future hold?

In the near future, trials of SoC plus STAT-C will be initiated in
difficult-to-treat populations (patients with advanced liver
disease, cirrhosis, recipients of liver transplantation or patients
with major comorbidities such as HIV coinfection). It remains to
be seen if there are safer regimens with less drug interactions,
especially with antiretroviral drugs (Seden 2010). As shown in
chapter 1, race is an important determinant of the therapy
response; as a consequence new HCV therapies should be also
studied in Asian, Afro-american and Latino populations in order
to fully characterize their efficacy and safety.
The predictive value of on-treatment viral kinetics will require
re-evaluation for the DAAs and their combinations. Although
evaluation of SVR at 6 months after treatment completion will
remain the gold standard for treatment success, there is growing
evidence indicating that SVR at 12 weeks after treatment
completion may be enough to predict long-term viral clearance.