Antiviral treatment for chronic HCV – Then and Now

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Hepatitis C (HCV) treatment has improved dramatically in recent years, both in terms of efficacy and tolerability, and continues to evolve, with promising breakthroughs on the horizon. Achieving a cure is now possible for many people with HCV.

Treatment goals

The goal of HCV treatment is to achieve a sustained virologic response (SVR). SVR is the medical term for eliminating HCV, sometimes called a virologic cure. It is the most important result in HCV treatment. SVR12 means that HCV is not detectable in the blood 12 weeks after treatment. SVR24 means that HCV is not detectable in the blood 24 weeks after treatment is completed. If you achieve SVR24 following HCV treatment, you are considered cured. Although SVR24 is the key goal, most people with SVR12 will also achieve SVR24.1,2

Achieving SVR is associated with a very high likelihood (almost 100%) of being free of HCV. SVR is also associated with increased likelihood of survival and decreased risk for liver transplantation, hepatocellular carcinoma (liver cancer), and other types of liver complications. Achieving SVR not only lowers your risk of death from liver disease, it also appears to lower your risk of death from other causes, including cardiovascular disease and cancer. This is important, because people with HCV are at increased risk of early death from a range of diseases, including liver and cardiovascular disease.3

If you have HCV and cirrhosis, having HCV treatment and achieving SVR can provide important benefits. However, if you have cirrhosis, achieving SVR does not mean that you are cured of liver disease. You may be virologically cured, and still have cirrhosis.

What drugs are used to treat HCV?

There are three types of medications used to treat HCV. They include:

  • Direct-acting antiviral medications (polymerase inhibitors and protease inhibitors)
  • Peginterferon
  • Ribavirin

Antiviral drug therapy for HCV

Interferon alfa
  • Peginterferon alfa-2a (Pegasys)
  • Peginterferon alfa-2b (Pegintron)
Ribavirin
  • Copegus
  • Rebetol
  • Ribasphere (generic)
  • Moderiba (generic)
Direct-acting antiviral medications
Protease inhibitors
  • boceprevir (Victrelis)
  • telaprevir (Incivek*)
  • simeprevir (Olysio)
Polymerase inhibitor
  • sofosbuvir (Sovaldi)
Multi-class combination
  • ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak)
  • ledipasvir and sofosbuvir (Harvoni)

*No longer marketed.

Peginterferon. Interferons are proteins that are naturally produced by the body and play an important role in the immune system. They are made by our cells in response to the entry of viruses, bacteria, and other harmful invaders. Interferons trigger an immune response and rally the cells to fight back. Interferons “interfere” with the virus’s ability to reproduce. There are three types of interferons. Interferon alfa (sometimes also spelled “alpha”) is the one used to treat HCV. Interferons do not remain active in the body for very long, so scientists modified them to increase the amount of time they stay in the body and remain active. Polyethylene glycol or PEG, for short, was added to interferon alfa to increase its activity, making it pegylated interferon alfa (or just peg interferon).4,5

Peginterferon has been an important part of treatment for HCV for many years. However, there are now several effective non-interferon treatments available and others in development. In the future, interferon-based treatment will probably play a diminishing role in HCV treatment.

Peginterferon is self-administered weekly by injection. There are two different peginterferon drugs used to treat HCV infection, peginterferon alfa-2a (Pegasys) and peginterferon alfa-2b (Pegintron). These two agents have comparable efficacy and safety. The side effects of peginterferon are much like having the flu. However, eventually peginterferon may cause other side effects, such as depression, fatigue, blood count irregularities, dry skin, and body aches. If you are being treated with interferon-based therapy for HCV infection, your doctor will be able to make many useful suggestions for managing the most common side effects associated with this type of treatment.4,5

Learn more about managing the side effects of interferon treatment.

Ribavirin. Ribavirin is a type of drug called a nucleoside analog. We don’t know exactly how ribavirin works, but when it is used with interferon, ribavirin interferes with the ability of HCV to reproduce or replicate. Ribavirin is used in combination with peginterferon and/or direct-acting antiviral agents to treat HCV infection. Two ribavirin brands are available, Copegus and Rebetol. There are also generic versions, such as Ribasphere and Moderiba, with efficacy and safety comparable to non-generic forms.6

Ribavirin is a pill or capsule, taken twice daily. The major side effect associated with ribavirin is anemia, which can be managed by lowering the dose. Other common side effects include rash, headache, cough and sinus problems, fatigue, insomnia, irritability, anxiety, dizziness, weakness, appetite loss, and nausea and vomiting.6

Direct-acting antiviral agents. Direct-acting antiviral agents (DAAs) are the newest medications used to treat HCV. Although there are many different types of DAAs, the ones currently available by prescription include protease inhibitors and polymerase inhibitors. In October 2014, Harvoni,  a combination pill of  ledipasvir and sovaldi, was approved for genotype 1 patients and is taken once daily for 8-24 weeks depending on degree of fibrosis and whether a patient is treatment naïve or a previous relapser or non-responder. Eight weeks can be considered in treatment-naïve patients without cirrhosis who have pretreatment HCV RNA <6 million IU/mL.  In December 2014, Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets)  was approved to treat patients with chronic hepatitis C virus genotype 1 infection, including those with advanced liver disease called cirrhosis. Patients with genotype 1a with cirrhosis must add ribavirin to Viekira Pak and treat for 24 weeks. Viekira Pak administered with ribavirin for 12 weeks may be considered for some patients based on prior treatment history. Both of these new treatments  have an SVR rate over 90%.

HCV protease inhibitors. Protease inhibitors target an important enzyme (the protease enzyme) that the Hepatitis C virus uses to form new copies of itself. HCV needs the protease enzyme in order to replicate or reproduce itself and to survive. Protease inhibitors block the ability of HCV to do this.7-9

Protease inhibitors are taken orally and used in combination with other drugs, such as peginterferon, ribavirin, or other DAAs to treat people with HCV genotype 1 infection. Three HCV protease inhibitors are currently available: simeprevir (Olysio), boceprevir (Victrelis), and telaprevir (Incivek). Olysio, which was recently approved by the US FDA, is a capsule taken daily along with peginterferon and ribavirin. The treatment lengths are 24 or 48 weeks. Because it is more convenient to take and is associated with fewer side effects, Olysio is generally preferred over Victrelis and Incivek.7-9 The most common side effects in studies in which Olysio was given in combination with peginterferon and ribavirin included skin rash, itching, and nausea. Olysio combined with peginterferon and ribavirin can cause reactions to sunlight.

Some physicians are using Olysio with the polymerase inhibitor, sofosbuvir (Sovaldi). This 12-week treatment regimen is used for HCV patients with advanced liver disease who may have difficulty tolerating peginterferon and ribavirin. Since this treatment regimen is not formally approved by the FDA, it is known as an off-label use.

Victrelis and Incivek are used in combination with peginterferon and ribavirin. However, with newer drugs on the market, Victrelis and Incivek are rarely used in the US. Both are taken multiple times daily with treatment durations ranging from 12 to 48 weeks. The most common side effects in studies in which Victrelis was given in combination with interferon included tiredness, nausea, headache, and change in taste. The most common side effects in studies in which Incivek was given in combination with interferon included itching, nausea, diarrhea, vomiting, anal or rectal problems, and change of taste. Less common serious side effects associated with Victrelis and Incivek included allergic reactions and blood problems (low red and white blood cell counts).7-9

HCV polymerase inhibitors. The recent approval of Sovaldi marked the introduction of yet another class of DAAs to treat HCV infection. Sovaldi is a polymerase inhibitor. It works against HCV by mimicking a molecular compound that inserts itself into a strand of RNA. This interferes with copying viral genetic material, blocking its ability to replicate or reproduce itself.10,11

Sovaldi is taken orally once daily in combination with peginterferon and/or ribavirin (depending on HCV genotype and other considerations). Treatment typically lasts from 12 to 24 weeks. The most common side effects in clinical trials testing Sovaldi as combination therapy included headache, fatigue, nausea, insomnia, and anemia.10,11 Some physicians are using Sovaldi with the protease inhibitor Olysio. This 12-week treatment regimen is used for HCV patients with advanced liver disease who may have difficulty tolerating peginterferon and ribavirin. Since this treatment regimen is not formally approved by the FDA, it is known as an off-label use.

Recommendations for treatment of HCV infection

The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) issued updated recommendations for the testing, management, and treatment of HCV infection. These recommendations spell out drug treatment regimens based on HCV genotype and other considerations, including whether prior antiviral treatment has been attempted without sufficient response, whether a person is co-infected with HIV and HCV, the extent of liver disease, and other special conditions.

AASLD/IDSA treatment recommendations2

Click to learn more about recommended treatments…
If you are starting treatment and…
  • Were not treated before
  • Relapsed after achieving SVR with prior treatment
If you did not respond to prior treatment…
  • If you were a nonresponder or a partial responder
If you have a special medical condition…
  • Co-infection with HIV/HCV
If you have a special medical condition…
  • Cirrhosis, liver transplant, impaired kidney function

AASLD=American Association for the Study of Liver Diseases; IDSA=Infectious Diseases Society of America; HCV=hepatitis C virus.

view references
  1. Chopra S. Overview of the management of chronic HCV infection. Di Disceglie AM, Bloom A, eds. Accessed at: www.uptodate.com. 2014.
  2. American Association for the Study of Liver Disease, Infectious Diseases Society of America. Recommendations for testing, managing, and treating HCV. Available at: http://www.hcvguidelines.org. Accessed April 24, 2014.
  3. Backus LI, Boothroyd DB, Phillips BR, Belperio P, Halloran J, Mole LA. A sustained virologic response reduces risk of all-cause mortality in patients with HCV. Clin Gastroenterol Hepatol 2011;9:509-16 e1.
  4. Pegylated interferon (peginterferon) alfa-2b: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  5. Di Bisceglie AM. Mechanism of action and efficacy of peginterferon for the treatment of chronic HCV infection. Chopra S, Bloom A, eds. Accessed at: www.uptodate.com. 2014.
  6. Ribavirin: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  7. Boceprevir: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  8. Simeprevir: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  9. Telaprevir: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  10. Sofosbuvir: Patient drug information. Uptodate. Accessed at: www.uptodate.com. 2014.
  11. Sovaldi (sofosbuvir) Prescribing Information. Janssen Therapeutics, Division of Janssen Products, LP. Titusville, NJ. 2013.
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