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Antiviral Treatment for Chronic HCV – Then and Now

Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and can cause serious complications and even death. Treatment is necessary to prevent HCV from progressing, and because the infection may not cause symptoms in its earliest stages, many people are diagnosed when the condition has advanced.1

Until the early 1990’s, there were no treatments available for HCV. Then two medications became available:

  • Interferon and later peginterferon, which mimics the body’s interferon (protein) in order to help fight viruses
  • Ribavirin, which is a nucleoside analogue that interferes with the virus’ ability to replicate1,2

While these two medications had low cure rates and several unpleasant side effects, they were the only options for many years.1

Evolution of HCV Treatment

  • Interferon
  • Ribavirin
  • Victrelis (boceprevir)
  • Incivek (telaprevir)
  • Olysio (simeprevir)
  • Sovaldi (sofosbuvir)
  • Harvoni (ledipasvir/sofosbuvir)
  • Viekira Pak (ombitasvir/paritaprevir/ritonavir and dasabuvir)
  • Technivie (ombitasvir/paritaprevir/ritonavir)
  • Daklinza (daclatasvir)
  • Zepatier (elbasvir/grazoprevir)
  • Epclusa (sofosbuvir/velpatasvir)
  • Viekira SR (ombitasvir/paritaprevir/ritonavir and dasabuvir)
  • Mavyret (glecaprevir/pibrentasvir)
  • Vosevi (sofosbuvir/velpatasvir/voxilaprevir)

The first direct-acting antivirals

The first direct-acting antivirals (DAAs) were approved by the U.S. Food and Drug Administration (FDA) in 2011: Victrelis™ (boceprevir) and Incivek® (telaprevir).1,2 (Note: Incivek is no longer marketed.3) These were protease inhibitors, which work by directly attacking the virus by targeting the NS3/4A protease enzyme. This action stops the virus from replicating. Protease inhibitors were used in combination with peginterferon and ribavirin, and they were specific for people with genotype 1 HCV, the most common strain of the virus. The protease inhibitors provided a vast improvement in treating HCV, improving sustained virological response (SVR) rates from 40% with interferon-based therapy to 64%-75%. (SVR is the goal of HCV treatment and means that the virus is undetectable in the blood.) However, the protease inhibitors only worked on genotype 1, and many people could not tolerate the medicines due to side effects like anemia (low red blood cell counts), fatigue, and rash, and complex dosing regimens.1

More treatment becomes available

Between 2013 and 2017, several new medications have become available that have changed the treatment protocols and greatly improved the cure rates for people with all genotypes of HCV. 1,4

Newer NS3/4A protease inhibitors

Newer NS3/4A protease inhibitors, which target the same enzyme as earlier medications, include:

  • Olysio® (simeprevir)
  • Grazoprevir
  • Paritaprevir
  • Voxileprevir
  • Glecaprevir1

NS5A inhibitors

NS5A is another protein that plays a critical role in how HCV spreads and multiplies in the body, and NS5A inhibitors block this protein, causing the virus to die out. NS5A inhibitors used to treat HCV include:

  • Daklinza™ (daclatasvir)
  • Ledipasvir
  • Elbasvir
  • Ombitasvir
  • Pibrentasvir
  • Velpatasvir1

NS5B inhibitors

NS5B is an enzyme that is essential for the virus to replicate. NS5B inhibitors block this enzyme and stop the virus from replicating. NS5B inhibitors used to treat HCV include:

Combination medications

Combination medications provide multiple medications in fewer pills, which makes them easier to take. In addition, the combination medications use drugs that have different mechanisms of action to attack the virus in multiple ways, which can lead to higher cure rates and less failure due to drug resistance.5

Combinaton medications used to treat chronic HCV infection include:

  • Harvoni® (ledipasvir/sofosbuvir)
  • Viekira Pak™ (ombitasvir/paritaprevir/ritonavir and dasabuvir)
  • Technivie™ (ombitasvir/paritaprevir/ritonavir)
  • Zepatier® (elbasvir/grazoprevir)
  • Epclusa® (sofosbuvir/velpatasvir)
  • Mavyret™ (glecaprevir/pibrentasvir)
  • Vosevi® (sofosbuvir/velpatasvir/voxilaprevir)1,4

Higher cure rates

With the addition of DAAs to treatment regimens, the percentage of people with HCV achieving a cure is nearing 100%. In addition, the newer regimens provide a shorter treatment time, with some achieving SVR in just 12 weeks.1

Challenges of new treatments

Cost of therapy can be a barrier, as the newer DAAs are expensive. As more time passes, generics will likely become available and provide a more inexpensive option.1

The ability of the virus to replicate and change also remains a challenge. HCV can become resistant to some drugs, requiring additional treatments in some cases. The treatment guidelines continue to evolve as new therapies become available, and researchers are learning more about drug resistance in HCV and how to overcome it.5

Written by: Emily Downward | Last reviewed: June 2019
  1. Burstow NJ, Mohamed Z, Gomaa AI, et al. Hepatitis C treatment: where are we now? International Journal of General Medicine. 2017;10:39-52. doi:10.2147/IJGM.S127689.
  2. Advances in medications to treat hepatitis C. HEP C 123, American Liver Foundation. Available at Accessed 3/2/18.
  3. Helfand C. Sovaldi forces Incivek off the hep C market as Vertex calls it quits. FiercePharma. Available at Accessed 3/2/18.
  4. Hepatitis C drug news for 2018 – no pipeline. Hepatitis Central. Available at Accessed 3/2/18.
  5. HCV Resistance Primer. American Association for the Study of Liver Diseases. Available at Accessed 2/28/18.