Antiviral Treatment for Chronic HCV - Then and Now

Reviewed by: HU Medical Review Board | Last reviewed: May 2023

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

Until the early 1990s, there were no treatments available for hep C. Then 2 medicines became available:1,2

  • Interferon and later peginterferon. This mimics the body’s interferon (protein) to help fight viruses.
  • Ribavirin, which is a nucleoside analogue. It interferes with the virus’ ability to grow.

While these 2 drugs had low cure rates and several unpleasant side effects, they were the only options for many years.1

The first direct-acting antivirals: A history

The first direct-acting antivirals (DAAs) were approved by the U.S. Food and Drug Administration (FDA) in 2011. They were Victrelis™ (boceprevir) and Incivek® (telaprevir). These drugs were protease inhibitors. Protease inhibitors stop certain chemical reactions in the cells. This keeps the HCV virus from growing (replicating). Victrelis and Incivek attacked the NS3/4A enzyme.

These first DAAs only worked for people with genotype 1 HCV, the most common strain of the virus. However, neither of these drugs are recommended or available in the United States as of March 2020.1,3,5

The DAAs vastly improved HCV treatment. Between 64 and 75 percent of people reached undetectable levels of virus in the blood compared to 40 percent with interferon-based therapy. However, the protease inhibitors only worked on genotype 1. Plus, many people could not tolerate the drugs due to side effects like anemia (low red blood cell counts), fatigue, and rash. They also had complex dosing regimens.1

More treatments arrive

Between 2013 and 2019, several new drugs came on the market. They changed treatment plans and greatly improved the cure rates for people with all genotypes of HCV.1,4,5

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

  • Grazoprevir
  • Paritaprevir
  • Voxileprevir
  • Glecaprevir1

NS5A inhibitors

NS5A is another protein that helps HCV spread and grow in the body. A group of drugs called NS5A inhibitors blocks this protein, causing the virus to die out. These drugs include:1

  • Ledipasvir
  • Elbasvir
  • Ombitasvir
  • Pibrentasvir
  • Velpatasvir

NS5B inhibitors

Then, NS5B inhibitors came on the market. NS5B inhibitors block the NS5B enzyme and stop HCV from growing. These drugs include:1

  • Sovaldi (sofosbuvir)
  • Dasabuvir
  • Combination medications

Combination drugs arrive

Combination drugs provide multiple medicines in fewer pills. This makes them easier to take. Plus, the combination medicines use drugs that attack the virus in multiple ways. This can lead to higher cure rates and less failure due to drug resistance.6

Combination drugs used to treat chronic HCV infection include:1,4

  • Harvoni® (ledipasvir/sofosbuvir)
  • Zepatier® (elbasvir/grazoprevir)
  • Epclusa® (sofosbuvir/velpatasvir)
  • Mavyret™ (glecaprevir/pibrentasvir)
  • Vosevi® (sofosbuvir/velpatasvir/voxilaprevir)

Between 2011 and early 2020, several HCV drugs were taken off the market. Drugs are usually discontinued because newer medicines are more effective with fewer side effects. Discontinued HCV drugs include:5

  • Daklinza
  • Incivek
  • Olysio
  • Technivie
  • Victrelis
  • Viekira XR and Viekira Pak (Viekira Pak is still used outside the United States)

Higher cure rates

With the addition of DAAs to treatment regimens, the percentage of people with HCV achieving a cure is nearing 100 percent. Plus, the newer regimens provide a shorter treatment time. Some people now achieve undetectable virus levels in just 12 weeks.1

Challenges of new treatments

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

The ability of the virus to grow 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. Researchers are still learning more about drug resistance in HCV and how to overcome it.6

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