Direct-acting antivirals (DAAs), also known as “specifically targeted antiviral therapy for hepatitis C” (STAT-C), are the most important new therapeutical options for hepatitis C.
Direct-acting antivirals (DAAs) are a collection of medications that directly attack the ability of a virus, such as hepatitis C, to make copies of itself (replicate). There are different kinds of DAAs that interfere at different stages of the replication cycle. Telaprevir (Incivek) and boceprevir (Victrelis)—the first DAAs available for hepatitis C—are both called protease inhibitors (PIs).
Telaprevir and boceprevir are new medications that can be added to a peg-interferon/ribavirin regimen for people with genotype 1 hepatitis C mono-infection. This is called “triple therapy”—since it is a combination of three medications: peg-interferon, ribavirin and either telaprevir or boceprevir. Telaprevir and boceprevir are not prescribed on their own (without peg-interferon and ribavirin) and they are not prescribed together.
Drug Resistance
What is drug resistance and why is adherence important?
Drug resistance occurs when a virus is able to make more copies of itself (replicate) despite proper doses of a medication—because the virus can resist the medication. Resistance does not happen with peg-interferon and ribavirin but it can happen with direct-acting antivirals such as telaprevir and boceprevir.
Medication schedules and correct doses are designed to keep enough drugs in the bloodstream to stop the virus from replicating. Missing doses means that drug levels in the body may, at least temporarily, drop too low to keep the virus under control. If the virus keeps making copies of itself while exposed to those low drug levels, it can quickly figure out how to make copies of itself even at the proper doses.
Research suggests that the amount of resistant virus declines over time after stopping to take the protease inhibitor. However, it is not clear if there are any long-term consequences if resistance develops.
Adherence—taking all the medications at the right times, every time, as prescribed by a healthcare provider—is one way to prevent resistance from developing. This helps maximize a person’s chance of clearing the virus.
What are some considerations for starting triple therapy?
Adding a protease inhibitor to a peg-interferon and ribavirin regimen has some benefits. It can:
- increase the chances of clearing the virus for people with genotype 1 hepatitis C mono-infection
- shorten the length of treatment for some people with genotype 1 hepatitis C mono-infection
- improve treatment response for people with genotype 1 hepatitis C mono-infection who tried treatment before and treatment was not successful for them
Still, triple therapy is not the right option for everyone. There are important potential challenges to consider, such as:
- Adding a PI makes the regimen more complicated, which might make adherence more difficult for some people. Both PIs increase the number of pills a person has to take and how many times a day treatment is taken. Adding a PI can also cause or increase certain side effects. How well a person adheres to a treatment regimen impacts treatment success.
- PIs may not be an acceptable treatment option for some women. Ribavirin can cause birth defects so if pregnancy is possible, both partners must use two forms of birth control during treatment and for six months after. However, protease inhibitors decrease the effectiveness of hormonal forms of birth control (such as birth control pills, injections, implants and skin patches). Intra-uterine devices, diaphragms with spermicide and barrier methods such as condoms are not affected by protease inhibitors.
- PIs and other medicines can affect each other and can also cause serious side effects. There are certain medicines that people cannot take with triple therapy that includes a PI. It is important for people to talk to their healthcare providers about any prescription and non-prescription drugs, vitamins and herbal supplements they take.
About Telaprevir
Telaprevir (Incivo in Europe and Incivek in the USA) is for patients with Genotype 1. It is a protease inhibitor that helps target the virus and is added to the current treatment of Interferon and Ribavirin. It will mean the patient will be taking a combination of 3 drugs.
Telaprevir can boost the success rate of clearing the virus from 50% to 80% and in some cases will shorten the time that a patient needs to be on treatment.
Telaprevir is taken orally three times a day (every 8 hours) in a pill form. It is taken during or right after a meal. Choosing foods with some fat content, such as cheese or toast with butter or peanut butter, will help the medication get into the bloodstream.
Foods for Incivek:
(should have more than 20g of fat with each dose)
- Nuts, cashews / pecans / almonds (1/3 cup)
- Avocado (1 whole)
- Olive oil (2 tablespoons)
- Peanut butter (3 tablespoons)
- Ice cream (1 cup)
- American or cheddar cheese (2 oz)
- Trail mix (1/2 cup)
- Potato chips (2 oz)
- Bagel with cream cheese (1)
- Potato Salad (1 cup)
- Muffins (1 muffin)
Telaprevir is made by Vertex.
Length of treatment
For people who have never received HCV treatment before, treatment with telaprevir, peg-interferon and ribavirin lasts for 12 weeks. Then, peg-interferon and ribavirin are continued for at least another 12 weeks. During those 24 weeks, a healthcare provider will monitor how treatment is working. Depending on how the virus is responding to treatment:
- treatment might be stopped (if the virus is not responding)
- a 24-week regimen might be enough to clear the virus
- treatment with peg-interferon and ribavirin (and not telaprevir) might continue for another 24 weeks
A similar approach is used for people who previously cleared their HCV virus while on peg-interferon and ribavirin but then had it return after the completion of treatment (this is called a relapse).
For people who previously started peg-interferon and ribavirin but stopped because treatment was not working, triple therapy lasts for 12 weeks and then peg-interferon and ribavirin are continued for another 36 weeks.
In clinical trials, about 70% of people who never received hepatitis C treatment before cleared the virus when the regimen included peg-interferon, ribavirin and telaprevir.
About Boceprevir
Victrelis is for patients with Genotype 1. It is a protease inhibitor that helps target the virus and is added to the current treatment of Interferon and Ribavirin. It will mean the patient will be taking a combination of 3 drugs. It can boost the success rate of clearing the virus from 50% to 80% and in some cases will shorten the time that a patient needs to be on treatment.
Boceprevir is taken orally three times a day (every 7-9 hours) in a pill form. It is taken during or right after a meal.
Foods for Victrelis:
(does not have a fat content requirement)
- Sweet potatoes
- Eggs
- Beans
- Crackers
- Fruits
- Dry nuts
- Vegetables / Salad
- Breads / Cereal / Rice / Pasta
- Beef / Chicken / Pork / Tofu
- Fish
- Milk / Yogurt / Cheese
Boceprevir is made by Merck
Length of treatment
People start off with four weeks of peg-interferon and ribavirin before adding boceprevir to their regimen on week 5. A healthcare provider will monitor how treatment is working. Depending on how the virus is responding to treatment:
- treatment might be stopped (if the virus is not responding)
- a person with a very good virological response to treatment might be able to stop treatment:
- at week 28 if the person has never tried hepatitis C treatment before; or
- at week 36 if the person tried treatment with interferon and ribavirin before but did not clear the infection
- the healthcare provider might recommend continuing treatment with peg-interferon and ribavirin (with or without boceprevir) for a total of 48 weeks of treatment
In clinical trials, about two-thirds of the people who never received hepatitis C treatment before cleared the virus when the regimen included peg-interferon, ribavirin and boceprevir.
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New Hep C Treatment Guidelines Spell Out Incivek and Victrelis Use
Revised treatment guidelines from the American Association for the Study of Liver Diseases (AASLD) outline a significant change in the standard of care for people with genotype 1 chronic hepatitis C virus (HCV) infection. Instead of 48 weeks of pegylated interferon and ribavirin, treatment should also include one of the two new protease inhibitors (PIs)—either Incivek (telaprevir) or Victrelis (boceprevir)—with the length of therapy based on the results of viral load testing at different time points, depending on which PI is used.
Generally, people can discontinue therapy after 24 weeks, provided that their HCV viral load is undetectable after four weeks of therapy with a PI-inclusive regimen and that the virus remains undetectable for the remaining 20 weeks. Forty-eight weeks of treatment is still recommended for people who have cirrhosis, and for certain repeat treatment-takers (called null responders).
The updated AASLD guidelines, published in October in Hepatology, were issued for health care providers treating people with either Incivek or Victrelis, both of which were approved in May 2011 for use in combination with pegylated interferon and ribavirin. Incivek and Victrelis have dramatically increased cure rates for both first-time and repeat treatment-takers with chronic HCV genotype 1 infection. However, adding a third drug also makes HCV treatment more complicated for patients and their doctors.
Because of these complications, which include side effects and the development of HCV drug resistance to the protease inhibitors, AASLD recommends curtailing HCV treatment when it is very unlikely to work. Since these “stopping rules” differ for each drug, clear guidance is provided for when to stop therapy with both drugs.
The updated AASLD guidelines refer clinicians to the drugs’ labeling, or detailed package insert, for information on managing side effects, although the guidelines authors do provide their own guidance on managing anemia. Anemia is a common side effect from ribavirin and the HCV protease inhibitors. During hepatitis C treatment, if anemia develops, people are either treated with a red blood cell growth factor, such as Procrit (erythropoietin), or given a lower dose of ribavirin. The authors noted that cure rates were similar no matter which strategy was used to manage anemia. Since growth factors are costly and add side effects, AASLD recommends reducing the ribavirin dose to manage anemia while maintaining full-dose Incivek or Victrelis.
The guidelines also stress that clinicians and their patients can use IL-28B genotype testing—a blood test that can predict responses to HCV treatment with pegylated interferon, ribavirin and either Incivek or Victrelis—to gain more information on the likelihood of treatment effectiveness and the length of treatment. The authors caution, however, that IL-28B testing should not be used to withhold PIs from patients who have more favorable IL-28B results (for example, a “CC” genotype) and may be more likely to be cured with pegylated interferon and ribavirin alone, given that adding a PI significantly boosts cure rates in people with all IL-28B variations, including the harder-to-treat “CT” and “TT” genoytpes.
In the United States, an estimated 70 percent of people with hepatitis C have genotype 1. Before Incivek and Victrelis were approved, genotype 1 was difficult to treat; cure rates were less than 50 percent. Now, adding a protease inhibitor to pegylated interferon and ribavirin means that first-time treatment-takers are much more likely to be cured and they may be able to shorten treatment from 12 to six months. Hepatitis C protease inhibitors will also help people who were unsuccessfully treated in the past.
Marc G. Ghany, from the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, coauthored the updated recommendations with four colleagues. Ghany and his peers note that the update is “intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case.”
Ghany and his coauthors based their recommendations on their years of experience treating hepatitis C, and on published results from clinical trials. Their recommendations were based on the strength of available scientific evidence, as well as their potential risks and benefits. As such, these guidelines offer a thorough overview of the results from clinical trials, followed by specific recommendations for treating different groups of patients with each drug (since they are used differently).
Guidance on HCV treatment for special populations is limited because of a lack of data in people coinfected with HIV and hepatitis C, transplant recipients and people with decompensated cirrhosis, but the updated guidelines do address some key aspects of HCV treatment, such as how to determine the proper duration of treatment and the best time to stop it, as well as how to manage common side effects from the new drugs.
The guidelines also underscore the risk of combining Incivek or Victrelis with certain drugs that are commonly used by people with hepatitis C, and the guides provide additional resources for medical providers to help avoid drug interactions that can prevent drugs from working or increase their side effects.
Unfortunately, the updated guidelines do not offer guidance on adherence, although it is crucial for successful HCV treatment. Incivek and Victrelis must be taken every eight hours, along with weekly injections and twice-daily ribavirin, often by people who already use additional medications.
Now that a cure is more likely for people with HCV genotype 1, the demand for treatment is sure to increase, and more non-specialist providers may be called upon to care for HCV patients. The revised guidelines are an important resource, since they incorporate the latest research results into clear and handy recommendations for busy clinicians.
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