Drug Resistance

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

Drug resistance occurs when viruses or bacteria become resistant to the drugs that are typically effective against them. Hepatitis C (HCV) drug resistance occurs when HCV becomes resistant to 1 or more direct-acting antiviral agents (DAA). DAAs are powerful tools in the fight against HCV. They have greatly improved the chances of a successful cure for most people with HCV. However, drug resistance is one of the important challenges of HCV treatment.1

HCV and genetic mutations

HCV grows very quickly in the body, producing billions of viruses daily. Each time the virus grows, a copy of the virus’s genetic material is made. This copying process is not precise. Small errors can occur. This creates genetic mutations (changes) to the genetic code.1

Some genetic mutations have no effect on the virus. Some mutations may even create a virus that no longer grows. However, certain genetic mutations can create a virus that is no longer susceptible to certain antiviral drugs. These kinds of mutations mean the drug is no longer able to stop the virus from growing.1

Because HCV is able to quickly mutate, the immune system is always trying to catch up with the virus as it makes lightly different versions of itself. Once the body has successfully eliminated 1 version of HCV, another modified version takes its place. Experts believe this process is why so many people with HCV develop chronic disease and why infection has been so hard to cure. These many genetic changes also interfere with HCV vaccine development.2

HCV drug resistance and DAAs

When a person with HCV receives a DAA, the drug may successfully kill most of the virus. The number of viral copies may even fall below detectable levels. This may suggest that a cure has been achieved. However, if some of the virus had a genetic mutation and survived attack by the DAA, this new version will continue to reproduce. Over time, it will re-establish the viral infection. This is what happens when a person achieves an initial response to treatment followed by a viral breakthrough.3

Drug-resistant HCV is more likely to occur when the levels of medicine in the body are lower than recommended. This may occur if a person does not take the recommended dose at the proper time. Drug resistance is also more common in people for whom a certain treatment fails to work.1

Certain genetic mutations can result in drug resistance to all medicines that work in a similar way. For example, if someone with HCV has been treated with a NS5A inhibitor (for example, Harvoni®) and the virus undergoes a change, the virus may become resistant to other NS5A inhibitors.4

Ways to overcome HCV drug resistance

Some tests can detect if HCV has specific mutations that make it resistant to certain drugs. Testing may be used in people with HCV who have had prior treatment. Testing may also be used in people who have not yet had treatment for HCV. The test results can help doctors choose which drugs are more likely to be effective for each person.1

Another way to overcome HCV drug resistance is to combine several drugs that work against HCV in different ways. This allows them to attack the virus in several ways. Increasing the length of treatment in cases where HCV is resistant to certain drugs may also help.1

It is important to stick to the treatment plan created by your doctor. This will help you avoid missing any doses, which decreases the chances of drug resistance.

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