Hepatitis C treatment factsheet: Harvoni (sofosbuvir + ledipasvir)

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.

How does Harvoni work?

Harvoni 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.

Who can use Harvoni?

Harvoni is 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 transplant.

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 history.




Genotype 1, 4, 5, 6


8 weeks (no cirrhosis, no previous treatment

12 weeks (no cirrhosis, previously treated)

24 weeks (no cirrhosis, previous treatment, lack of future options)

24 weeks (cirrhosis or post-transplant with cirrhosis)

Genotype 1,4,5,6

With ribavirin

12 weeks (no cirrhosis, previous treatment or post- transplant)

12 weeks (cirrhosis, including decompensated cirrhosis)

Genotype 3

With ribavirin

24 weeks (cirrhosis and/or previous treatment)

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 combination pill.

Recommended uses for people with HIV and HCV co-infection are the same as for HIV-negative people.

How effective is Harvoni?

Harvoni works 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 treatment.

Harvoni treatment response

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 genotype 1.

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.

The 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.

The 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.

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.

Harvoni’s 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.

What are the side-effects of Harvoni?

Harvoni is 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 male partners.

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.

Harvoni can 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.

How can I get Harvoni?

Harvoni is 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 your country.