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.

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

A computer graphic of the solids molecular model of a protease inhibitor. (Reproduced by permission of

Photo Researchers, Inc.

)

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) ]