Direct-acting antiviral (DAA) agents are medications that doctors use to treat hepatitis C. DAA agents contain a combination of drugs to destroy the hepatitis C virus (HCV).

Direct-acting antiviral agents (DAA) drugs for hepatitis C.Share on Pinterest
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There are different classes of DAA agents that combine to target specific parts of the virus in order to destroy it.

In this article, we look at the currently available DAA agents for treating HCV, treatment times, side effects, and effectiveness of a DAA regimen.

The following chart shows a list of recommended first-line DAA treatments.

Brand nameGeneric nameType or classDAA per tabletIs ribavirin (RBV) needed?
Harvoni• ledipasvir
• sofosbuvir
• NS5A polymerase inhibitor
• NS5B nucleotide polymerase inhibitor
2sometimes
Zepatier• elbasvir
• grazoprevir
• NS5A polymerase inhibitor
• NS3/4A protease inhibitor
2sometimes
Epclusa• sofosbuvir
• velpatasvir
• NS5B nucleotide polymerase inhibitor
• NS5A polymerase inhibitor
2sometimes
Vosevi• sofosbuvir
• velpatasvir
• voxilaprevir
• NS5B nucleotide polymerase inhibitor
• NS5A polymerase inhibitor
• NS3/4A protease inhibitor

3no
Mavyret• glecaprevir
• pibrentasvir
• NS3/4A protease inhibitor
• NS5A polymerase inhibitor
2no
SovaldisofosbuvirNS5B polymerase inhibitor1yes
DaklinzadaclatasvirNS5A polymerase inhibitor1sometimes
OlysiosimeprevirNS3/4A protease inhibitor1sometimes
Viekira Pak• ombitasvir
• paritaprevir
• ritonavir
• dasabuvir
• NS5A polymerase inhibitor
• NS3/4A protease inhibitor
• CYP3A inhibitor
• NS5B palm polymerase inhibitor
4yes

DAA agents are a type of medication that treats hepatitis C by destroying HCV. DAA agents target different stages of the HCV life cycle.

Each DAA tablet contains a combination of drugs to fight the virus more effectively.

There are three different classes of DAA agents:

  • NS3/4A protease inhibitors
  • NS5A polymerase inhibitors
  • NS5B polymerase inhibitors

Each class attacks the virus in a different way. The class of DAA people require can depend on any previous treatment they have had for HCV.

HCV has different genotypes, and a regimen of DAA agents can target all HCV genotypes. The HCV genotypes are 1a, 1b, 2, 3, 4, 5, and 6.

According to the American Liver Foundation (ALF), in the United States, around 75% of people with HCV have genotype 1a or 1b. Around 10–20% of individuals with HCV have genotype 2 or 3.

The currently available DAA agents include the following combination drug brands:

  • Harvoni: This is a combination of ledipasvir and sofosbuvir. Harvoni is an NS5B nucleotide polymerase inhibitor and NS5A polymerase inhibitor.
  • Zepatier: This combines elbasvir and grazoprevir. Zepatier is an NS3/4A protease inhibitor and NS5A polymerase inhibitor.
  • Epclusa: This is a combination of sofosbuvir and velpatasvir. Epclusa is an NS5B nucleotide polymerase inhibitor and NS5A polymerase inhibitor.
  • Vosevi: This combines sofosbuvir, velpatasvir, and voxilaprevir. Vosevi is an NS3/4A protease inhibitor, NS5B nucleotide polymerase inhibitor, and NS5A polymerase inhibitor.
  • Mavyret: This is a combination of glecaprevir and pibrentasvir. Mavyret is an NS3/4A protease inhibitor and NS5A polymerase inhibitor.

The Food and Drug Administration (FDA) also approved Sovaldi in 2013, which is still available. Sovaldi is the brand name for sofosbuvir.

Sovaldi is an NS5B polymerase inhibitor, suitable for people with the 1, 2, 3, or 4 HCV genotype without cirrhosis. It can also treat HCV in those under the age of 3 years with genotypes 2 or 3 without cirrhosis.

Healthcare professionals will prescribe Sovaldi alongside antiviral agents, such as RBV. RBV is an antiviral prescription drug to treat HCV.

Other DAA agents include:

  • Daklinza: This is the brand name for daclatasvir, which is an NS5A inhibitor.
  • Olysio: This is the brand name for simeprevir, which is an NS3/4A protease inhibitor. A healthcare professional may prescribe this in combination with other DAA agents.
  • Viekira Pak: This is a combination of:
    • ombitasvir, an NS5A inhibitor
    • paritaprevir, an HCV NS3/4A protease inhibitor
    • ritonavir, a CYP3A inhibitor
    • dasabuvir, an HCV non-nucleoside NS5B palm polymerase inhibitor

According to a 2020 cohort study, DAA agents are highly effective and are able to cure HCV in 90% of cases.

The study followed 51,478 people with HCV who were receiving Medicare. DAA treatment led to a significant decrease in mortality rates in people with and without cirrhosis.

The study concludes that treatment with DAA agents could improve HCV outcomes regardless of the stage of the condition.

The regimen and dose will depend on the HCV genotype a person has.

According to a 2018 study, research does not advise the use of RBV with all DAA regimens, due to negative side effects.

The research states that people may need to take RBV alongside DAA medication if previous treatments have not been effective at curing HCV or if a person has advanced cirrhosis.

According to the ALF, the regimen and doses for DAA agents are as follows:

All HCV genotypes

A healthcare professional may prescribe the following:

DrugIngredientsNumber of tablets per dayDurationWith RBV?
Epclusa• 400 milligrams (mg) sofosbuvir
• 100 mg velpatasvir
1 tablet with or without food12 weekssometimes, if a person has advanced cirrhosis
Mavyret• 100 mg glecaprevir
• 40 mg pibrentasvir
3 tablets once per day with or without food8, 12, or 16 weeksno
Vosevi• 400mg sofosbuvir
• 100mg velpatasvir
• 100mg voxilaprevir
1 tablet with food12 weeksno

HCV genotype 1

A healthcare professional may prescribe the following:

DrugIngredientsNumber of tablets per dayDurationWith RBV?
Daklinza with Sovaldi• 60 mg daclatasvir
• 400 mg sofosbuvir
• 1 tablet of Daklinza
• 1 tablet of Sovaldi
12 weekssometimes
Harvoni• 90 mg ledipasvir
• 400 mg sofosbuvir
1 tablet with or without food8, 12, or 24 weekssometimes
Olysio with Sovaldi• 150 mg simeprevir
• 400 mg sofosbuvir
• 1 capsule of Olysio with or without food
• 1 tablet of Sovaldi with or without food
12 or 24 weekssometimes
Viekira Pak• 12.5 mg ombitasvir
• 75 mg paritaprevir
• 50 mg ritonavir
• 250 mg dasabuvir
• 2 tablets containing ombitasvir, paritaprevir, and ritonavir twice per day
• 1 tablet of dasabuvir twice per day
12 or 24 weekssometimes
Zepatier• 50 mg elbasvir
• 100 mg grazoprevir
1 tablet with or without food12 or 16 weekssometimes

HCV genotype 2

A medical professional will prescribe Sovaldi.

A person will take 1 tablet of 400 mg sofosbuvir once per day with or without food. A person can take it in combination with RBV alongside food.

HCV genotype 3

A doctor will prescribe the following:

DrugIngredientsNumber of tablets per dayDurationWith RBV?
Daklinza with Sovaldi• 60 mg daclatasvir
• 400 mg sofosbuvir
• 1 tablet of Daklinza
• 1 tablet of Sovaldi
12 weeksno
Sovaldi with RBV• 400 mg sofosbuvir
• RBV
• 1 tablet of Sovaldi
• 1 tablet of RBV
24 weeksyes

HCV genotype 4

A doctor will prescribe the following:

DrugIngredientsNumber of tablets per dayDurationWith RBV?
Harvoni• 90 mg ledipasvir
• 400 mg sofosbuvir
1 tablet with or without food12 weekssometimes
Sovaldi400 mg sofosbuvir1 tablet with or without food24 weeksyes
Zepatier• 50 mg elbasvir
• 100 mg grazoprevir
1 tablet with or without food12 or 16 weekssometimes

HCV genotypes 5 and 6

A doctor will prescribe Harvoni, consisting of 90 mg of ledipasvir and 400 mg of sofosbuvir, with or without food for 12 weeks.

The ALF states that the time it takes for DAA agents to treat HCV depends on the type of DAA an individual is taking.

DrugTime it takes to work
Epclusa12 weeks
Mavyret8, 12, or 16 weeks, depending on:
• the HCV genotype
• previous HCV treatment
• whether a person has asymptomatic cirrhosis, meaning without symptoms
Vosevi12 weeks for those without cirrhosis and those with asymptomatic cirrhosis
Harvoni8, 12, or 24 weeks
Zepatierin most cases, 12 weeks; sometimes, 16 weeks
Sovaldi12 or 16 weeks
Daklinza with Sovaldi12 weeks
Olysio with Sovaldi12 or 24 weeks
Viekira Pak12 or 24 weeks

Each DAA drug may cause side effects, which can include the following:

DrugSide effects
Harvonifatigue
headache

In combination with RBV, Harvoni may cause:
weakness
• headache
cough
Zepatier• fatigue
• headache
nausea

In combination with RBV, Zepatier may cause:
anemia
• headache
• fatigue
shortness of breath
rash
itching
Epclusa• headache
• fatigue

In combination with RBV, Epclusa may also cause:
• nausea
diarrhea
insomnia
• anemia
Vosevi• headache
tiredness
• nausea
• diarrhea
Mavyret• headache
• fatigue
Sovaldi• headache
• fatigue
Daklinza• headache
• fatigue
OlysioAfter 12 weeks of treatment, a person may experience:
• fatigue
• headache
• rash
• itching
• sensitivity to light

After 24 weeks of treatment, diarrhea and dizziness may also occur.
Viekira PakSide effects without RBV include:
sleep problems
• itching
• nausea

In combination with RBV, Viekira Pak may cause:
• tiredness
• nausea
• itching
• weakness
• skin reactions, such as a rash

DAA agents are medications that are highly effective at treating HCV. People may need to take a course of tablets for 8–24 weeks or longer, depending on each individual case.

DAA agents may cause some side effects, such as headache and fatigue. In some cases, people will need to take DAA medication alongside RBV.