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Protease Inhibitors

Protease inhibitors

Protease inhibitors (pronounced PRO-tee-ace in-HIH-bi-ters) are a new type of drugs that slow down the spread of HIV (human immunodeficiency virus) inside a person's body. HIV is the virus that causes the disease AIDS (acquired immunodeficiency syndrome). The drugs work by interrupting the way the AIDS virus uses a healthy cell to make copies of itself. Although not a cure for this disease, protease inhibitors have proven to be a powerful anti-HIV drug, especially when taken in combination with certain other drugs.

AIDS

AIDS is a contagious disease caused by a virus that disables the immune system, which is the body's natural defense against diseasecausing organisms. HIV enters the body through the bloodstream, duplicates itself rapidly, and eventually destroys the body's immune system. This leaves the victim susceptible to other infectious diseases that usually prove fatal.

AIDS cannot be spread by the type of casual contact that usually occurs between family and friends. HIV must somehow enter the bloodstream to infect a person, and the most common way for this to happen is through some form of sexual contact that allows bodily fluids from one person to enter that of another. This is what occurs during any type of sexual intercourse or sexual penetration of a person's body. Another way is for an infected intravenous drug user to share a needle with another person. HIV has also been transmitted to an unborn child by its infected mother, and until programs for blood screening were created, HIV had also been transmitted by blood transfusions.

Words to Know

AIDS (acquired immunodeficiency syndrome): A disease of the immune system believed to be caused by the human immunodeficiency virus (HIV). It is characterized by the destruction of a particular type of white blood cell and susceptibility to infection and other diseases.

Immune system: The body's natural defense system that guards against foreign invaders and that includes lymphocytes and antibodies.

Virus: A package of chemicals that are far smaller than the living cells they infect. Viruses are not classified as living organisms, since they cannot grow and reproduce on their own, but rely on a host cell to make copies of themselves.

How a virus works

Although there is no cure as yet for AIDS, scientists have discovered drugs that can slow down the spread of HIV once it gets into a person's body. They were able to do this by understanding how viruses work in the body. Like any other virus, HIV depends on the cell it first infects to make new copies of itself. Viruses cannot grow or reproduce on their own. Because of this, viruses are not even considered to be living organisms. However, when a virus infects a cell, it takes over the cell's metabolism, or the chemical reactions that go on inside, and basically gives a new set of instructions to the cell's command center. Once the cell obeys, and it must obey, the new virus copies then break out of the cell and go on to infect other cells, doing the same thing to them.

In people infected with HIV, there are over ten billion new copies of the virus made every day. So if the virus-copying is not stopped quickly, HIV spreads rapidly throughout the body. The AIDS virus has a favorite cell that it first attacks. This is known as the "T helper cell" or the "CD4 cell." These helper cells are important since they tell other infectionfighting cells to get working. Since HIV infects the helper cells first and destroys them, the body's natural immune system is eventually worn down and weakened. The victim eventually becomes susceptible to other infections that he or she would normally have no trouble resisting, and often, AIDS patients die from a variety of fungal, parasitic, or viral infections. It is when a person's helper cells drop below a certain level that an HIV infection becomes a case of AIDS.

How protease inhibitors work

Protease inhibitors are antiviral drugs that interrupt how HIV uses a healthy cell to make copies of itself. Studies of how HIV works have shown

that the virus produces an enzyme or protein called protease that it must have to reproduce itself. Without protease, which cuts long chains of proteins and enzymes into shorter chains (which it needs to start the process), HIV cannot make copies of itself. The new class of drugs are called protease inhibitors because they "inhibit" or discourage something from happening. What they do specifically is to "gum up" the protease "scissors" so that they cannot do their cutting job. Protease inhibitors not only greatly reduce the number of new HIV copies that are made, they also make those that do manage to get produced defective in some way, so that they cannot go on and infect new cells. Although protease inhibitors are not a cure in that they cannot get rid of the HIV in an infected person' body, they can reduce the amount of virus in the blood by 99 percent.

Protease inhibitors were first developed by drug researchers in 1994, and a year later the U.S. Food and Drug Administration (FDA) approved the first version to be used in combination with other types of drugs that also worked at suppressing the spread of HIV in the cells. Since then, several types of protease inhibitors have been introduced and more are being studied. So far, protease inhibitors are the most powerful anti-HIV drugs available, allowing many people infected with the virus at least to try to live a somewhat normal life.

Although they do have some serious side effects and must be taken properly, the biggest problem with protease inhibitors may be the ability of HIV to learn how to resist them. Like any virus, HIV has the ability to change its chemical or genetic makeup and develop "resistance" to something that formerly used to defeat it. Researchers have found that once infected people stop their drug therapy, the virus rebounds in the body. So far, this means that people must continue the therapy throughout their lives. At present, researchers are not sure how long protease inhibitors will work in a person infected with HIV, but they are hopeful.

[See also AIDS (acquired immunodeficiency syndrome) ]

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Protease Inhibitors

Protease Inhibitors

Definition

A protease inhibitor is a type of drug that cripples the enzyme protease. An enzyme is a substance that triggers chemical reactions in the body. The human immunodeficiency virus (HIV) uses protease in the final stages of its reproduction (replication) process.

Purpose

The drug is used to treat selected patients with HIV infection. Blocking protease interferes with HIV reproduction, causing it to make copies of itself that cannot infect new cells. The drug may improve symptoms and suppress the infection but does not cure it.

Precautions

Patients should not discontinue this drug even if symptoms improve without consulting a doctor.

These drugs do not necessarily reduce the risk of transmitting HIV to others through sexual contact, so patients should avoid sexual activities or use condoms.

Description

Protease inhibitors are considered one of the most potent medications for HIV developed so far.

This class of drugs includes indinavir (Crixivan), ritonavir (Norvir), nelfinavir (Viracept), amprenavir (Agenerase), lopinavir plus ritonavir (Kaletra), saquinavir (Fortovase), and a new drug called atazanavir (Reyataz). Reyataz received approval from the U.S. Food and Drug Administration (FDA) in mid-2003 and was the first protease inhibitor approved for once-daily dosing. Several weeks or months of drug therapy may be required before the full benefits are apparent.

The drug should be taken at the same time each day. Some types should be taken with a meal to help the body absorb them. Each of the types of protease inhibitor may have to be taken in a different way. In most cases, protease inhibitors are part of a combination therapy, used in conjunction with other classes of HIV drugs.

Risks

Common side effects include diarrhea, stomach discomfort, nausea, and mouth sores. Less often, patients may experience rash, muscle pain, headache, or weakness. Rarely, there may be confusion, severe skin reaction, or seizures. Some of these drugs can have interactions with other medication, and indinavir can be associated with kidney stones. Diabetes or high blood pressure may become worse when these drugs are taken. Reyatraz has been shown to have fewer side effects than some protease inhibitors, though it can interact with other medications, including certain heart medications and antidepressants.

Experts do not know whether the drugs pass into breast milk, so breastfeeding mothers should avoid them or should stop nursing until the treatment is completed.

Resources

PERIODICALS

"HIV Drugs Approved as of August 2003." AIDS Treatment News July 25, 2003: 4.

LoBuono, Charlotte. "FDA Gives Bod to First Once-daily Protease Inhibitor." Drug Topics July 21, 2003: 16.

Wilson, Billie Ann. "Understanding Strategies for Treating HIV." Medical Surgical Nursing 6 (April 1, 1997): 109-111.

ORGANIZATIONS

National AIDS Treatment Advocacy Project. 580 Broadway, Ste. 403, New York, NY 10012. (888) 266-2827. http://www.natap.org.

KEY TERMS

Human immunodeficiency virus (HIV) The virus that causes AIDS.

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protease inhibitor

protease inhibitor (prō´tē-ās´), any of a class of drugs that interfere with replication of the AIDS virus (HIV), by blocking an enzyme (protease) necessary in the late stages of its reproduction. Clinical trials of the protease inhibitor indinavir have shown it to be especially beneficial in combination with the anti-HIV drugs AZT and 3TC, which act by blocking a different enzyme, reverse transcriptase. Saquinavir, the first member of the class to be marketed, was approved for use in 1995 by the Food and Drug Administration.

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protease inhibitor

protease inhibitor n. one of a class of antiretroviral drugs used in the treatment of HIV infection and AIDS. They inhibit the action of protease produced by HIV, required by viral growth and replication. Protease inhibitors include atazanavir (Reyataz), indinavir (Crixivan), lopinavir (Kaletra), and tipranavir (Aptivus).

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