Protease inhibitors treat certain viral infections by preventing the virus from making more copies of itself. They’re a critical part of HIV treatment. There are also protease inhibitors that help treat hepatitis C and COVID-19. Common side effects include nausea, vomiting and rash.
Protease inhibitors (PIs) are medications that treat viral infections. They work by preventing a virus from making more copies of itself. They’re most commonly used as an antiretroviral to manage HIV/AIDS. They can also be used to treat hepatitis C and COVID-19.
Some protease (pronounced “PRO-tee-ayz”) inhibitors can be taken on their own (monotherapy), but many are used in combination with other antiviral medications. When they’re used to help another medication be more effective, they’re called a “booster.”
Protease inhibitors are only approved to treat specific viral infections. Protease inhibitors can be used as part of treatments for:
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Proteases break long chains of proteins into smaller ones. This activates the smaller proteins to perform certain functions.
In viruses, the smaller proteins go on to create more copies of the virus. Protease inhibitors block protease so it can’t cut proteins into their active pieces. This prevents viruses from making more copies of themselves that infect your cells.
Since each virus has its own protease, different types of PIs are used to treat HIV, hepatitis C and COVID-19. You can recognize protease inhibitors by how their names end: drugs ending in “-navir” treat HIV and those ending in “-previr” treat hepatitis C.
These are examples of antiretroviral protease inhibitors for HIV treatment. These PIs block HIV-PR, the protease HIV uses to make more copies of itself:
These are examples of antiviral protease inhibitors for hepatitis C treatment. These PIs block NS3/4A serine protease (this is what the hepatitis C virus uses to make more copies of itself):
Paxlovid® is a combination of protease inhibitors (nirmatrelvir and ritonavir) that treats COVID-19. Nirmatrelvir is a 3C-like (3CL) protease inhibitor. 3CL is the protease that SARS-CoV-2, the virus that causes COVID-19, uses to make more copies of itself.
Your provider will select protease inhibitors based on:
Make sure to tell your provider about any other medications you’re taking and any other conditions you have. This can reduce your risk of serious interactions or complications.
Benefits of protease inhibitors include:
Protease inhibitor side effects and complications vary depending on which one you’re taking, what other medications you’re taking and your overall health.
Not all types have the same risk of complications. Talk to your healthcare provider about the risks and side effects of taking protease inhibitors so you know what to expect.
How long you need to be on a protease inhibitor depends on what kind of viral infection you’re treating:
Ask your provider about reducing your risk of complications or side effects. You may be able to avoid some side effects by:
Eating a meal with fat increases your body’s absorption of some protease inhibitors. This allows them to work better. Ask your provider if you should take your PI with food and what kind of food to take it with.
Call your healthcare provider if you have unexpected side effects or concerns about your treatment. Seek medical attention immediately if you have signs of severe side effects, including:
A note from Cleveland Clinic
Protease inhibitors are an important part of treatment plans for chronic viral illnesses. They can keep HIV undetectable and help cure hepatitis C. Talk to your provider about any concerns you have about treatment with protease inhibitors. Together, you can work on a treatment plan that works best for you.
Last reviewed by a Cleveland Clinic medical professional on 03/24/2023.
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