What Are Direct-Acting Antivirals for HCV Treatment?
Direct-acting antivirals (DAAs) are a newer class of drugs used to treat hepatitis C. DAAs target specific steps in the hepatitis C virus (HCV) life cycle. DAAs have shorter treatment times, fewer side effects, and higher SVR rates than older drugs. SVR means the hep C virus is not detectable in the blood, or “cured”. DAAs work by targeting the virus directly, making them more effective than older treatments.
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HCV is an virus that makes its own proteins to help it grow (replicate). Some of these proteins, or enzymes, are called:1-6
- NS3/4A protease
- NS5B RNA-dependent RNA polymerase
- NS5A protein
DAAs stop these proteins from working so that the virus cannot finish its life cycle and grow.
What are DAAs?
DAAs fall into 4 main types. Each type targets 1 or more of these proteins in order to stop the hep C virus life cycle and lower the body’s viral load. Most DAAs are taken in combination with other DAAs to improve how well they work. Ribavirin and peginterferon also are sometimes added to a DAA to improve how it attacks the virus.1,6
Typically, most patients can take DAAs without experiencing major side effects or complications (they are normally well-tolerated). However, because these drugs stimulate an immune reaction, they can also increase the risk of hepatitis B virus (HBV) reactivating. Before starting a DAA, as well as during treatment, your doctor should monitor you for HBV and for signs of liver problems.2
NS3/4A protease inhibitors for HCV treatment
NS3/4A protease inhibitors target the NS3/4A protease enzyme, which is needed for the virus to grow and thrive. These drugs may also weaken the virus in other ways. These drugs are mainly used to treat HCV genotype 1. Or, they may be used in combination with other HCV drugs to attack the virus from multiple angles.1,3
NS3/4A protease inhibitors currently approved to treat HCV include Grazoprevir, Paritaprevir, Voxileprevir, and Glecaprevir.
Compared to newer HCV medicines, NS3/4As are more complicated to take, have more side effects, and more drug interactions. It is also easier for HCV to develop resistance to the NS3/4As than some of the newer drugs.3
NS5B is an enzyme that is essential for the virus to replicate. NS5B inhibitors block this enzyme and stop the virus from replicating. These drugs are generally well tolerated and are less likely to develop resistance to the virus. NS5Bs also tend to work equally well across many genotypes. NS5B inhibitors used to treat HCV include Sovaldi (sofosbuvir) and Dasabuvir.1
NS5A protein inhibitors
These drugs target the NS5A protein, a protein that helps HCV grow. NS5A inhibitors work on all HCV genotypes. However, NS5A inhibitors have different levels of toxicity and HCV may more easily develop resistance to this class of drug. In general, these drugs work better when combined with peginterferon and ribavirin. For genotype 1, NS5As work better when used with other DAAs and ribavirin.3
Generic names of NS5A protein inhibitors currently sold are:
Many DAAs are not designed to be taken alone, but work better when used in combination with one another. Currently available combination DAAs include:2,6
- Epclusa (sofosbuvir and velpatasvir)
- Harvoni (ledipasvir and sofosbuvir)
- Zepatier (elbasvir and grazoprevir)
- Mavyret™ (glecaprevir and pibrentasvir)
- Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir)
Potential side effects of DAAs
While DAAs are a huge improvement over the first drugs available for HCV, they do come with potential side effects. The side effects depend on which drug you take but the most common include:4
- Diarrhea and abdominal pain
- Nasal drip or sore throat
Please note: The side effects listed above do not include all possible side effects. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment.
Things to know about DAAs
The safety of ribavirin-free DAAs has not been tested in women who are pregnant or breastfeeding. Women should not become pregnant while taking a DAA that contains ribavirin. Male partners who are taking a DAA with ribavirin should take appropriate measures to prevent pregnancy during treatment and for 6 months following treatment.5
Everyone should be tested for liver function, HIV, and HBV before taking DAAs. Anyone taking a DAA should be monitored regularly for signs of liver cancer.5
DAAs react poorly with many other types of prescription and over-the-counter drugs. It is important to talk with your doctor and pharmacist about any other medicine or supplements you are taking before starting a DAA.5