Page 76 - The Flying Publisher Guide to Hepatitis C Treatment

76 | Hepatitis C Treatment

Resistance testing is likely to become a part of the treatment
algorithm with the introduction of DAAs. Extensive knowledge of
the impact of these mutations on the phenotypic characteristics
and on the replicative fitness of the viral population will be
important (Kuntzen 2008) in order to tailor therapeutic decisions
for the management of the HCV infected patient.
It is expected that the HIV model of development of highly
active combined therapies, consisting of at least 3 drugs with
different mechanisms of action will be reproduced for HCV, in an
attempt to obtain effective interferon-free regimens. With such
combinations, HCV may become the first chronic viral infection
to be cured. While sufficient suppression of HIV RNA and HBV
DNA can only be achieved by long-term administration of potent
antiviral drugs, HCV RNA may be completely eradicated from the
infected individual after a limited duration of treatment. This is
foreseeable due to the fact that, unlike HIV (that replicates
through a proviral DNA subsequently integrated into the
lymphocytes nucleus), or HBV (that replicates through a cccDNA
that may integrate into the hepatocyte nucleus), HCV replication
is entirely intra-cytoplasmic and is not accompanied by the
establishment of extrahepatic reservoirs. In a viral kinetic model
for the pharmacokinetics of telaprevir, a rapid decrease in the
second slope of viral decline was found, four fold higher than
with standard interferon therapy. According to these data, a
combination triple therapy administered for 7-10 weeks might
be sufficient to eradicate the virus in fully compliant patients
(Guejd 2011). Patients who ultimately fail to clear the virus with
combination STAT-C regimens may still have improvements in
liver histology that can be further sustained by introduction of a
separate group of anti-fibrotic agents.

Outlook
The SoC for first-line treatment of HCV genotype 1 will most
likely soon become a triple combination of a PI, either
boceprevir or telaprevir, with PegIFN/RBV. Individualized
treatment must take into account baseline viral, host and disease