For HCV genotype 1 – the most common
type in the US and Europe – there are two main strategies using direct-acting
antivirals: use the HCV NB5S polymerase inhibitor sofosbuvir (Sovaldi) with whatever you have at hand,
or combine a potent HCV protease inhibitor with one or two other drugs,
according to Prof. Foster.
Gilead Sciences' sofosbuvir/ledipasvir
(Harvoni) has the advantage of being
a once-daily single-tablet regimen. It cures HCV in more than 95% of people with genotype 1 who do not have cirrhosis in 8 weeks with virtually no side-effects, and a similar
proportion of people with cirrhosis in 12 weeks in combination with
HCV protease inhibitor regimens
include AbbVie's paritaprevir-based '3D' regimen (sold as Viekirax/Exviera, Viekira Pak or Viekira XR) and Merck's
grazoprevir/elbasvir coformulation (Zepatier).
An investigational AbbVie regimen containing the protease inhibitor ABT493 plus
ABT530 looks promising so far and could bring more competition – and lower
prices – to the market.
Both approved protease inhibitor
regimens have sustained virological response rates similar to those of the
sofosbuvir combination. The AbbVie regimen used to be more complex, requiring
multiple pills and twice-daily dosing, but the US Food and Drug Administration (FDA)
recently approved a once-daily extended release version.
The caveat with the AbbVie regimen –
and probably all protease inhibitors, Prof. Foster suggested – is that if a
person has or has ever had decompensated cirrhosis, these drugs can lead to
worse liver disease and potentially death.
"It's really almost too good to
be true," Prof. Foster said. "You apply these drugs, your patients get
cured." He acknowledged, however, that things aren't always that simple,
as there are some issues of drug interactions and resistance that must be
HCV genotype 3 is a
"pussycat" and easy to treat in people without cirrhosis, but becomes
harder to treat in people with cirrhosis, he noted. The recently approved
sofosbuvir/velpatasvir coformulation (Epclusa)
is effective against genotype 3 – and all other HCV genotypes – and does not require
"We're not quite there yet"
with genotype 3, Prof. Foster concluded, and it is important to treat these
patients early, while they still have milder liver disease, "so you won't
end up with harder-to-treat cirrhotics."
Treatment failure with the new
direct-acting antivirals in people with HCV genotype 1 "is so rare that unless
you look for it, you won't see it," Prof. Foster said. In the old days of
interferon-based therapy, 90% efficacy for genotype 3 "would have looked
pretty good, but today it's not good enough."
In daily clinical practice, a
provider likely won't see the difference between 95% and 98% efficacy. However,
Prof. Foster stressed, "if we're going to eliminate hepatitis C, we need
98% – 90% efficacy will blow chances of elimination. To hit the 98% SVR rates
we dream of, we need to make sure the right drugs are given to the right people
in the right way."