Sonal Kumar, MD, MPH
Assistant Professor of Medicine Weill Medical College of Cornell University New York, New York
Ira M. Jacobson, MD
Chief of the Division of Gastroenterology and Hepatology
Vincent Astor Distinguished Professor of Medicine
Weill Medical College of Cornell University
New York, New York
With the global burden
of HCV, the need for effective, well-tolerated treatment regimens is
great. Elucidation of the HCV life cycle has allowed for newer drugs to
be developed, overcoming some of the major disadvantages of prior
standard of care with IFN-based therapy. The DAAs are anticipated to
completely replace IFN as the foundation of HCV treatment.
Among the major advantages of these oral regimens, beyond their
increased efficacy, has been their relatively clean safety profile.
Although AEs are common, they generally are mild, including headache,
fatigue, and insomnia, and trivial relative to those of telaprevir and
boceprevir.46
The low rate of discontinuation in all the trials further attests to
the tolerability of the regimens, even in those containing RBV. In
addition, the once-daily dosing and limited drug–drug interactions have
minimized the AEs of treatment for most patients. As newer medications
and regimens are approved, the next dilemma will be to determine the
ideal combination of medications and treatment duration for each
patient. Ideally, predictors of response to treatment would aid in the
decision making, but none has consistently been identified. Although one
study has suggested that early viral kinetics may identify those with a
higher risk for relapse,21 such predictive value has not been gleaned from the Phase III databases.
Importantly, these new regimens also have been able to overcome
baseline factors previously associated with poorer outcomes, including
G1a subtype, race, non-CC IL28B allele, and prior treatment
history. Although rates of treatment failure now appear to be minimal
and routes to treatment failure have all but eliminated nonresponse and
viral breakthrough, some patients will relapse. SOF has been associated
in vitro with a S282T signature mutation, but it is
replicatively unfit54 and rarely found in samples from SOF-treated
relapsers, providing a foundation for retreatment with a SOF-containing
regimen in these failures. Now that the fundamental paradigm shift
toward IFN-free regimens is imminent, further research will be needed to
identify effective salvage therapies for patients who have failed both
nucleotide-containing and nucleotide-free combination regimens.
Read moreLabels: interferon-free, new treatments, treatments, which treatment to use