Harvoni is a
new medication used to treat hepatitis C. It is a combination pill containing sofosbuvir (sold
separately as Sovaldi) plus
ledipasvir. It was approved in Europe in November 2014 for treatment of adults with
genotype 1 or 4 chronic hepatitis C, and for some people with genotype 3.
For many people with these genotypes, Harvoni is an interferon-free and
ribavirin-free hepatitis C treatment option. Some people with harder-to-treat
disease may do better if they add ribavirin. Successful treatment reduces the
risk of long-term complications of hepatitis C such as liver cancer or needing
a liver transplant.
contains two direct-acting antiviral drugs that target different steps of the
hepatitis C virus (HCV) lifecycle. Sofosbuvir is a nucleotide analogue HCV polymerase
inhibitor, meaning it blocks the polymerase enzyme which the virus must use to
reproduce. Ledipasvir is an HCV NS5A replication complex inhibitor that
interferes with another protein HCV uses to reproduce.
indicated for use by adults with chronic hepatitis C, meaning infection lasting
more than six months. It is approved for people with HCV genotypes 1 or 4, and
for some people with genotype 3. Genotype 1 is the most common type in Europe.
Harvoni can be
used by people being treated for hepatitis C for the first time (known as ‘treatment-naive’)
and for retreatment of people who were not cured with previous interferon-based
therapy (known as ‘treatment-experienced’).
Harvoni has also
been tested in people with HIV and HCV co-infection. Response rates and
side-effects are similar to those of HIV-negative people, and Harvoni can be used with most HIV
medications. People with HIV and HCV co-infection who want to take Harvoni should do so under the care of a
doctor who has experience treating both infections.
Harvoni can be
used by people with all stages of liver disease, including compensated cirrhosis,
decompensated cirrhosis (laboratory abnormalities or symptoms of poor
liver function) and people who are awaiting or have received a liver
How is Harvoni taken?
Harvoni is taken
as a single pill once-daily with or without food. The length of treatment, and
whether Harvoni should be taken with
ribavirin, depends on HCV genotype, amount of liver damage and prior treatment
Most people with HCV genotype 1 or 4 without liver
cirrhosis should take Harvoni without
ribavirin for 12 weeks. Previously untreated people with genotype 1 and no
cirrhosis can consider shortening treatment to 8 weeks. Some people who were
previously unsuccessfully treated may benefit from lengthening treatment to 24
People with HCV genotype 1 or 4 who have compensated
cirrhosis should take Harvoni without
ribavirin for 24 weeks. People with decompensated cirrhosis and those who are
awaiting or have received a liver transplant should take Harvoni with twice-daily ribavirin pills for 24 weeks.
People with HCV genotype 3 who have compensated cirrhosis
or prior treatment failure can take Harvoni
with ribavirin for 24 weeks (although this genotype does not have as much data
from clinical studies).
Harvoni is not
approved for people with HCV genotypes 2, 5 or 6. People with genotype 2 should
use sofosbuvir (Sovaldi) plus
ribavirin, not the Harvoni
Recommended uses for people with HIV and HCV co-infection
are the same as for HIV-negative people.
effective is Harvoni?
better for some people than for others. Several factors predict how well
someone will respond, including HCV genotype, extent of liver damage and
previous treatment history.
People with advanced liver disease may not respond as
well as those with mild or moderate liver fibrosis. People who are new to
treatment might have a better chance of being cured than those who did not
respond to prior treatment. These factors may be overcome by longer treatment
or by adding ribavirin, which helps prevent relapse.
Other factors that traditionally predict poor response
to interferon-based therapy do not make as much difference with interferon-free
People with sustained virological response, who still
have undetectable HCV viral load 12 weeks after finishing treatment (known as
‘SVR12’), are considered cured.
The phase 3 ION studies showed that the drugs in Harvoni, sofosbuvir plus ledipasvir, cured
94% to 100% of previously untreated and treatment-experienced people with HCV
ION-1 showed that previously untreated people with or
without liver cirrhosis had high cure rates with 12 weeks of treatment. ION-2,
a study of previously treated people, found that 24 weeks worked better than 12
weeks for those with cirrhosis. ION-3 showed that 94% of previously untreated
people without cirrhosis were cured in just 8 weeks. In all of these studies,
adding ribavirin did not improve cure rates.
ERADICATE trial found that Harvoni
without ribavirin for 12 weeks cured HCV in 98% of previously untreated people
with HIV and HCV co-infection who had HCV genotype 1 and no cirrhosis.
In the SYNERGY study, 95% of participants with HCV
genotype 4 - which included previously untreated
and treatment-experienced people with and without cirrhosis - were cured using Harvoni without ribavirin for 12 weeks.
SOLAR-1 trial showed that Harvoni
plus ribavirin taken for 12 or 24 weeks cured 87% to 89% of people with HCV genotype
1 or 4 and decompensated cirrhosis. The same regimen led to early sustained response (‘SVR4’)
for more than 95% of liver transplant recipients with advanced fibrosis or
compensated cirrhosis, although response rates were lower for people with
decompensated liver disease.
Preliminary findings from the ELECTRON-2 study
showed that Harvoni plus ribavirin for
12 weeks cured 100% of previously untreated people with HCV genotype 3, but the
cure rate fell to 64% without ribavirin.
effectiveness in ‘real world’ use may be somewhat lower than cure rates seen in
clinical trials, in part because patients may be sicker or have other
conditions that make treatment more complicated.
the side-effects of Harvoni?
generally well tolerated. The most common side-effects seen in clinical trials
were fatigue and
headache. The drugs in Harvoni have
not been tested in pregnant or breastfeeding women. Ribavirin
can cause side-effects including anaemia. It can also cause birth defects, so
it should not be used by pregnant women, women planning to conceive, or their
Does Harvoni interact with other drugs?
The drugs in Harvoni
can interact with certain drugs processed by a protein known as ‘P-gp’, including
some tuberculosis (TB) medications, psychiatric drugs and cholesterol-lowering
drugs. Harvoni should not be taken
with rosuvastatin (Crestor) or herbal
products containing St. John's wort.
raise levels of the HIV drug tenofovir (Viread,
also in several antiretroviral coformulations), so people taking these drugs
together should have their kidney function checked regularly. Information about
other specific drug interactions is available online at www.hep-druginteractions.org.
I get Harvoni?
available by prescription in several European Union countries to treat people
with hepatitis C genotypes 1 or 4, and in some cases genotype 3. When to start
treatment will depend on a number of factors, including severity of liver
damage (as determined by FibroScan or
a liver biopsy). Ask your GP or liver specialist if Harvoni may be a good option for you, and if it is available in