HIV is a virus that goes through many steps during its' life cycle. Once HIV infects a human cell, the virus uses

proteins and chemicals inside that cell to make more copies of itself. Protease is a chemical, known as an enzyme, that HIV needs in order to make new viruses. Protease inhibitors (PIs) block the protease enzyme. When protease is blocked, HIV makes copies of itself that can't infect new cells. Studies have shown that protease inhibitors can reduce the amount of virus in the blood and increase CD4 cell counts. In some cases these drugs have improved CD4 cell counts, even when they were very low or zero.

The biggest news and the greatest benefits to people with HIV came when protease inhibitors (PIs) were discovered and made into anti-HIV treatments. When people started taking them in combination with other drugs, the number of people who became ill from opportunistic infections, or died from AIDS, dropped by about 70%.

However, studies have also shown that these effects can wear off over time. This happens because HIV makes more of itself all the time. Each new HIV virus that gets made may be slightly different than the one it made before. The new protease that the virus has made may resist the drugs that worked for viruses with the older type of protease. This is what scientists call Drug Resistance. When this happens, other protease inhibitors usually become less effective as well.

The best way to avoid drug resistance is to stop or reduce HIV production in the body. The less HIV made in the body, the less chance of a virus created that's resistant to anti-HIV drugs. To keep HIV levels as low as possible, it's recommended that protease inhibitors be taken in combination with at least two other anti-HIV drugs. This is called Highly Active Anti-Retroviral Therapy or HAART. Studies have shown that when certain protease inhibitors are combined, the anti-HIV effect is increased, which can help prevent or overcome resistance. This is called Protease Boosting. Some doctors will order a drug resistance test to determine a patient's resistance profile, in order to decide the best drug combination to use.

There are eight FDA approved protease inhibitors so far, they are: amprenavir (Agenerase), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), ritonavir (Norvir), saquinavir (Fortovase), and nelfinavir (Viracept). .

Protease Inhibitors are pills that need to be taken at least twice a day. It's very important to stick to the exact dose and schedule for taking a protease inhibitor. That way, you keep enough protease inhibitor in your body to block HIV. Make sure to find out how the protease inhibitor should be taken, for example, on an empty or full stomach. For anyone with HIV, a thorough medical check-up is a good idea before starting protease inhibitor treatment.

Five years of HAART did not produce the hoped for cure, but these drugs have helped many people to greatly improve their helath. Unfortunately, long-term side effects have become an especially difficult problem. Every PI has a common menu of possible side effects that you may experience. Some people experience none of them. Others have a very hard time tolerating the drugs.

Diabetes - There is a government warning about protease inhibitors causing high blood sugar and diabetes. Symptoms to watch out for include increased thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin. These symptoms usually show up 10-11 weeks after starting the protease inhibitor.

Lipodystrophy - Another side effect being reported with HAART combinations are problems with how your body absorbs fats and other nutrients. The symptoms can include high levels of a type of fat called cholesterol, and other fats known as triglycerides. High blood fat levels can make you feel very tired, and generally ill. Other symptoms are a swollen belly, big breasts, loss of weight in the face so you look very thin, and loss of muscle in the arms and legs. These side effects have been given the name lipodystrophy. One of the most serious lipodystrophy-related problems is high level of fats (cholesterol and triglycerides) in the blood. High levels of fats in the blood can increase the risk of heart attacks and pancreatitis. Due to these risks, it's important to have your cholesterol and triglyceride levels checked regularly if you're taking Protease Inhibitors.

Many doctors now recommend you be given another test that measures how much fat is in your blood. The test should be done before starting HIV treatment, and at least every three months afterwards. The test is called a fasting lipid test. The fasting part means you don't eat about 12 hours before you take the test. You should keep to a low fat diet if the results of the test are high. A nutritionist can help make sure there's very little fat in your diet. If you're at serious risk for heart disease because of things like smoking or existing heart problems, you may have to stop taking the HIV drugs you're on. After a while of not taking any anti-HIV drugs, your doctor may want you to try a different combination.

Liver Toxicity - Other less common side effects caused by protease inhibitors include increases in liver function tests, which can indicate toxicity to the liver. Anyone taking a protease inhibitor should have his or her liver function closely monitored. Blood tests can be done that check the health of the liver and other organs. These tests look for problems, such as hepatitis infections, that could effect how the protease inhibitors work, or increase the chance of side effects. Protease inhibitors can make hepatitis worse, so it's important to know if you have hepatitis B and/or C before starting a protease inhibitor.

Keep in mind that in order for protease inhibitors to be effective, they need to be taken on time, and at the right dose. It is important to tell your doctor if you are having trouble sticking to schedule because of side effects. There are ways to manage these side effects. Your doctor may reduce the dose, or switch you to another drug.

Protease inhibitors can affect the absorption of other drugs by the body. These are called drug interactions. Your health care provider should go over any potential drug interactions with you when starting a protease inhibitor. It may be necessary to change or alter the dose of certain medications to make sure that the protease inhibitor can work properly. Some herbs and supplements, such as St. John's Wort and garlic supplements, can affect the level of protease inhibitors in your blood. You should always tell your health care provider if you are taking herbs and supplements.