How Do Protease Inhibitors Treat HIV?

Protease inhibitors are pharmaceutical drugs that are prescribed for the treatment of Hepatitis C and Human Immunodeficiency Virus (HIV) infections. Once HIV has entered the body, it enters a variety of immune system cells. The virus then uses these immune cells as a factory to produce copies of itself. In the early stages of infection, the HIV virus proliferates as the number of important immune cells, called CD4 T cells, sharply declines. The goal of drug treatments for HIV is to reduce or eliminate the number of copies of HIV in the body (also called the "viral load"). Protease inhibitors, first approved for HIV treatment in the United States in 1995, have the ability to both reduce viral load and increase CD4 T cell count. Protease inhibitors are frequently taken in combination with other drugs, and have been credited with reducing HIV deaths by as much as 70 percent.

HIV is a virus that depends on self-replication for its continued survival. The HIV virus makes billions of copies of itself, killing the host cells it uses for replication. Once HIV infection has occurred and HIV has entered CD4 T cells, it releases its genetic information and a variety of enzymes into the host cell's nucleus. The virus then uses the host cells material to begin the process of replicating its own genetic material. Once this material is replicated, it exits the host nucleus and is processed further to manufacture new HIV. This final step of replication depends on an enzyme, called protease, to complete the replication process successfully. The main function of protease inhibitors is to disable the activity of the protease enzyme. By rendering protease unable to function HIV can not complete its replication process, reducing and sometimes eliminating the HIV viral load.

Although protease inhibitors are an amazing and important treatment for HIV infection, they are by no means a cure. Protease inhibitors may lose their effectiveness to prevent HIV replication. This loss of effectiveness is called "drug resistance" and is more likely to occur over a long period of time. Drug resistance takes place when the HIV virus is continually exposed to a particular protease inhibitor. Because the HIV virus is attempting replication at a fast pace, the chance of mutations occurring in the genetic material is high. If a mutation takes place that enables to virus to complete its replication successfully, this mutated virus may then pass on that ability to other viruses, rendering the protease inhibitor's actions ineffective. For this reason, it is important to keep the virus level as low as possible--the fewer viruses present, the less likely it is that one will develop a mutation. Because of the possibility of drug resistance, HIV treatment is monitored continuously for effectiveness, and multiple medications are often used to reduce the viral load as much as possible.

Resources

• Facts about protease inhibitors from the AIDS Treatment Data Network.