HCV Treatments by Genotype

HCV treatment can vary based on the genotype of the virus, as well as other treatments attempted or failed. Ultimately, your provider will help you determine the best treatment regimen for your specific situation, but there are many guidelines that exist that provide typical treatment recommendations for each genotype. Your provider will consider guidelines like these as well as other factors including efficacy, adverse effects, drug interactions, past medical history (including kidney or liver problems, as well as HIV and other medical concerns), duration, stage of fibrosis, and insurance coverage. Most treatment regimens range from 12 to 24 weeks; however, some can reach up to 48 weeks. It is important to note that treatment guidelines are continually changing, which is why it is important to always consult your physician for the most recent information. Currently, the three main classes of medications for HCV are interferon, ribavirin, and direct-acting antivirals (DAA’s).

Interferon

Interferon treatments, like pegylated interferon (peginterferon) mimic proteins in our body that are designed to fight off infections.1 As your body is fighting off infections it produces interferons. These proteins are largely responsible for the fatigue, nausea, and other symptoms we commonly associate with the flu. Interferons are given via an injection, and used to be the main form of treatment for all individuals with HCV. Interferon can be administered with or without ribavirin. Interferon treatment is slowly being replaced by direct-acting antivirals which have higher rates of sustained virologic response, and a better rate of treatment completion due to their fewer, and more tolerable, side effects. Interferon can be used for many different genotypes, however, it has the lowest success rate for genotype 1. Common side effects of interferon include, but are not limited to:

  • Flu-like symptoms (chills, fever, headaches, generalized aches and pains, and poor appetite)
  • Fatigue
  • Drowsiness
  • Nausea
  • Vomiting
  • Ribavirin

    Ribavirin is not a stand-alone treatment, and is used across genotypes depending on what it is used in conjunction with. Ribavirin can be used alongside both DAA’s and interferon. The decision to add ribavirin to your treatment will be made by your provider, and can be influenced by the main medication your treatment will include, as well as the presence and severity of cirrhosis. The side effects that accompany ribavirin are often the product of other medications taken with it. For example, ribavirin taken with peginterferon still produces flu-like symptoms.

    Direct-Acting Antivirals

    Direct-acting antivirals (DAA’s) are a relatively newer class of medication that acts to target specific steps in the HCV viral life cycle.2 The goals of DAA’s are to shorten the length of therapy, minimize side effects, target the virus itself, and improve sustained virologic response rate. HCV is an RNA molecule that makes its own structural and non-structural proteins that help it replicate and assemble new virions. Due to their high rates of sustained virologic response and minimal side effects, DAA’s are slowly replacing interferon treatment. Genotype 1 has the most DAA treatment options, however, all other genotypes have at least one DAA option. Deciding which DAA to use depends on the genotype, as well as if the patient is treatment-naïve (meaning never experiencing HCV treatment) or treatment-experienced (meaning tried and failed other treatment options).

    Treatment options for HCV Genotype 1

    Genotype 1 HCV was previously the hardest to treat, as its response to interferon was the least impressive. Now, there are six DAA-driven treatment options for both genotypes 1a and 1b, with 1b typically having the higher success rate of the two. For individuals with genotype 1 HCV without cirrhosis or with compensated cirrhosis, who are either treatment-naïve or have failed treatment with peginterferon and ribavirin, the treatment options are as follows:

    • Harvoni (Ledipasvir-sofosbuvir)
    • Epclusa (Sofosbuvir-velpatasvir)
    • Zepatier (Elbasvir-grazoprevir)
    • Technivie (Ombitasvir-paritaprevir-ritonavir) plus Exviera (dasabuvir), with or without ribavirin
    • Viekira Pak (ombitasvir-paritaprevir-ritonavir tablet with accompanying dasabuvir tablet)
    • Viekira XR (dasabuvir-ombitasvir-paritaprevir-ritonavir)
    • Olysio (simeprevir) plus Sovaldi (sofosbuvir) or peginterferon and ribavirin
    • Daklinza (daclatasvir) plus Sovaldi (sofosbuvir)
    • Mavyret (glecaprevir-pibrentasvir)

    For individuals with prior protease inhibitor exposure, including telaprevir, simeprevir or boceprevir, this list is the same, with the exception of Technivie and Simeprevir with Sovaldi. With previous exposure to Sovaldi (sofosbuvir), this list shrinks even further to include only Harvoni and Epclusa. For individuals with decompensated cirrhosis, the use of DAA’s is not recommended unless under direct supervision. Potential DAA’s to be used under supervision for genotype 1 with decompensated cirrhosis are Harvoni, Epclusa, and Daklinza with Sovaldi.3,4

    Treatment options for HCV Genotypes 2 and 3

    Genotype 2 HCV shows strong success rates with peginterferon and ribavirin alone. However, there are a few DAA’s indicated for use by those with genotype 2 HCV without cirrhosis or with compensated cirrhosis, regardless of treatment history. These include:

    • Epclusa (Sofosbuvir-velpatasvir)
    • Daklinza (daclatasvir) plus Sovaldi (sofosbuvir)
    • Sovaldi (sofosbuvir) plus ribavirin (with or without peginterferon)
    • Mavyret (glecaprevir-pibrentasvir)

    With Epclusa being the first choice therapy when other treatment options have failed.

    Genotype 3 HCV is similar in treatment options to genotype 2 HCV, with one additional DAA option. Regardless of treatment history, there are several DAA’s indicated for use by those with genotype 3 HCV without cirrhosis or with compensated cirrhosis. These include:

    • Epclusa (Sofosbuvir-velpatasvir)
    • Daklinza (daclatasvir) plus Sovaldi (sofosbuvir)
    • Zepatier (Elbasvir-grazoprevir)
    • Sovaldi (sofosbuvir) plus ribavirin (with or without peginterferon)
    • Mavyret (glecaprevir-pibrentasvir)

    With Epclusa being the first choice therapy when other treatment options have failed.5

    For individuals with decompensated cirrhosis, the use of DAA’s is not recommended unless under direct supervision. Potential DAA’s to be used under supervision for genotype 2 or 3 HCV with decompensated cirrhosis are Epclusa plus ribavirin as well as Daklinza plus Sovaldi.

    Treatment options for HCV Genotype 4

    Genotype 4 HCV has several interferon-free treatment options that have high efficacy rates in comparison to their interferon-only containing counterparts. Genotype 4 treatments for individuals without cirrhosis or with compensated cirrhosis, regardless of treatment history are:

    • Harvoni (Ledipasvir-sofosbuvir)
    • Epclusa (Sofosbuvir-velpatasvir)
    • Zepatier (Elbasvir-grazoprevir)
    • Technivie (Ombitasvir-paritaprevir-ritonavir) plus ribavirin
    • Sovaldi (sofosbuvir) plus ribavirin
    • Olysio (simeprevir) plus peginterferon and ribavirin
    • Mavyret (glecaprevir-pibrentasvir)

    Ribavirin may be added in conjunction with several of the above DAA’s if patients are treatment-experienced.6

    For individuals with decompensated cirrhosis, the use of DAA’s is not recommended unless under direct supervision. Potential DAA’s to be used under supervision for genotype 4 HCV with decompensated cirrhosis are Harvoni and Epclusa, both in addition to ribavirin.

    Treatment options for HCV Genotype 5 and 6

    Genotype 5 and 6 currently have the same treatment options available. Genotype 5 and 6 treatments for individuals without cirrhosis or with compensated cirrhosis, regardless of treatment history are:

    • Harvoni (Ledipasvir-sofosbuvir)
    • Epclusa (Sofosbuvir-velpatasvir)
    • Sovaldi (sofosbuvir) plus ribavirin
    • Mavyret (glecaprevir-pibrentasvir)

    Like other genotypes, treatment with peginterferon and ribavirin is also a possibility if DAA treatments aren’t effective, however, the efficacy rate of this alternative treatment is substantially lower than the DAA treatment options.6

    For individuals with decompensated cirrhosis, the use of DAA’s is not recommended unless under direct supervision. Potential DAA’s to be used under supervision for genotype 5 and 6 HCV with decompensated cirrhosis are Harvoni and Epclusa in addition to ribavirin, the same as genotype 4 HCV.

    Written by: Casey Hribar | Last reviewed: August 2017.
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