Outcome of New Direct Acting Agents For Hepatitis C A Community Based Experience
Status:
Unknown status
Trial end date:
2016-11-01
Target enrollment:
Participant gender:
Summary
Chronic Hepatitis C virus (HCV) infection is the leading cause of advanced liver disease
worldwide. The virus successfully evades host immune detection and has highly restricted
requirements for growth in vitro that for many years hampered efforts to find a safe,
uncomplicated, and reliable oral antiviral therapy. Ten years after discovery, pegylated
interferon-alpha and ribavirin (PR) treatment for 24-48 weeks became the standard of care
(1-5). PR therapy offered limited performance and availability across the diverse spectrum of
HCV disease and was fraught with excessive and often limiting side effects. The first direct
acting agents (DAAs) were protease inhibitors (PIs) that were introduced in 2011 and could
only be used only in combination with PR because of concerns for rapid PI viral resistance.
Although the first generation PIs added increased efficacy to the PR regimen, they also added
new side effects and untoward drug interactions (6-8). Sofosbuvir (SOF) is a potent
nucleoside inhibitor (NI) that has recently been approved for treatment of HCV. The drug has
low toxicity, high resistance barrier, and minimal drug interactions with other HCV DAAs such
as PIs and anti-NS5A agents. SOF is safe and effective across different viral genotypes,
disease stages, and special patient groups such as those co-infected with HIV. When used in
combination with ribavirin or another DAA, SOF has revolutionized the HCV treatment spectrum
and set the stage for nearly universal HCV antiviral therapy. Sustained virologic response
(SVR12) for SOF plus ribavirin and pegylated interferon (PR) is 90% for genotype 1 and 85-94%
for genotypes 2 and 3 (9-16). SOF plus simeprevir (protease inhibitor) showed a 94% SVR12 for
genotype 1 (9-16). More so than any other anti-HCV drug developed to date, SOF offers the
widest applicability for all infected patients yet can be given in a personalized regimen to
maximize performance