Protease inhibitors are medications that help slow the progression of HIV by blocking the enzyme “protease,” which HIV cells need to develop and mature. Blocking this enzyme prevents the virus from making copies of itself.

Protease inhibitors are a type of antiretroviral therapy (ART) medication. These medications reduce the amount of HIV in a person’s blood. This helps control the virus and maintain a person’s overall health.

This article describes how protease inhibitors work and outlines some of the side effects and possible drug interactions associated with these medications. We also provide information on how doctors measure HIV treatment success.

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HIV is a virus that attacks cells of the immune system. Specifically, HIV damages white blood cells called CD4 T lymphocytes or “CD4.” Without sufficient numbers of these cells, a person becomes more susceptible to infections and disease.

Protease inhibitors are drugs that can help slow the progression of HIV. They work by blocking the enzyme “protease.”

HIV cells need protease in order to develop and mature. Without protease, HIV cells are unable to self-replicate, and this results in a low viral load.

The term “viral load” refers to the amount of virus in a person’s blood. A low viral load ensures that CD4 levels remain high enough to fight off infections and disease.

Protease inhibitors are one of seven types, or “classes,” of antiretroviral therapy (ART) drugs. These drugs all aim to reduce a person’s viral load.

Medical professionals categorize ART drugs into the different classes according to their mechanism of action. An ART regimen typically consists of three drugs from at least two classes.

Although ART does not cure HIV, it helps people with the virus live longer and decreases transmission of the virus.

The protease inhibitors approved by the Food and Drug Administration (FDA) include:

  • atazanavir sulfate (Reyataz)
  • darunavir ethanolate (Prezista)
  • fosamprenavir calcium (Lexiva)
  • ritonavir (Norvir)
  • saquinavir mesylate (Invirase)
  • tipranavir (Aptivus)
  • indinavir sulfate (Crixivan)
  • nelfinavir mesylate (Viracept)

Combination drugs combine two or more ART drugs from different classes into a single pill. FDA-approved combination protease inhibitors include:

  • lopinavir/ritonavir (Kaletra)
  • cobicistat/darunavir ethanolate (Prezcobix)
  • atazanavir sulfate/cobicistat (Evotaz)

Protease inhibitors can cause side effects. Some examples are outlined below.

Common side effects

The most common side effects of protease inhibitors include:

  • Dyslipidemia: Unhealthy levels of fats or “lipids” in the blood, such as cholesterol and triglycerides.
  • Lipodystrophy: A condition in which some parts of the body lose fat while others gain fat.
  • Lipoatrophy: The widespread loss of subcutaneous fat, which is fat that lies just beneath the skin.
  • Insulin resistance: A condition in which the body’s cells become less able to absorb and use glucose from the blood.
  • Cardiovascular disease: Conditions affecting the heart and blood vessels.
  • Cerebrovascular disease: Conditions affecting blood vessels in the brain.

The FDA notes that protease inhibitors can also cause serious liver problems and increase bleeding in individuals with hemophilia, a condition in which the blood does not clot as it should.

When to see a doctor

The FDA recommends people see a doctor if they experience any of the following side effects while taking protease inhibitors:

Protease inhibitors can interact negatively with a range of medications, including but not limited to:

The FDA warns that some protease inhibitor drug interactions may cause serious side effects or even death.

A person should let their doctor know about all prescription and over-the-counter medications, as well as any dietary or herbal supplements, they are taking.

A 2021 study reports the following as key indicators of HIV treatment success:

Viral load

Viral load is a measure of the amount of HIV copies in the blood. A low count indicates suppression of the virus, which is the primary treatment goal. Viral suppression means someone has less than 200 copies of HIV per milliliter of blood.

CD4 cell counts

Doctors often report viral load together with the CD4 level. Because CD4 is an essential part of the immune system, it indicates a person’s risk of contracting opportunistic infections. These are infections that occur more frequently or are more severe in people with impaired immunity.

The normal CD4 level ranges from 500–1,500 cells per cubic millimeter.

Quality of life

While doctors currently measure HIV treatment success according to viral load and CD4 levels, the authors of the 2021 study propose adding a third measurement: quality of life. This would include factors such as:

  • physical, psychological, and mental symptoms
  • financial difficulties
  • legal issues

Protease inhibitors are a class of antiretroviral therapy (ART) medications used for the treatment of HIV. They work by blocking the enzyme “protease,” which HIV cells need in order to develop, mature, and self-replicate.

Taking protease inhibitors in combination with other ART medications can help keep the viral load low and CD4 levels high. This can help a person stay healthy while also preventing HIV transmission.

While protease inhibitors are important in HIV management, they can cause potentially serious side effects. A person should notify their doctor if they experience concerning symptoms, such as:

  • breathing difficulties
  • severe skin rash
  • unusual muscle pain

People should also be aware that protease inhibitors can interact dangerously with other medications and supplements. Anyone taking protease inhibitors should let their doctor know if they are taking any other prescription or nonprescription drugs, as well as any herbal supplements or vitamins.

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