Studies have also shown that these effects can wear off over time. This happens because HlV makes more of itself all the time, and 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 not react at all to a drug that worked for the older type of protease. This is what scientists call resistance. When the virus becomes resistant to one protease inhibitor, it is usually less affected by other protease inhibitors, too.

The best way to avoid drug resistance is to prevent as much HIV production in the body as possible. If anti-HIV treatment is needed, the goal of treatment should be to reduce HIV levels as much as possible. The less HIV being made in the body, the less chance of a virus being made that's resistant to the 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 now called Highly Active AntiRetroviral Therapy or HAART, and has been shown to help people live longer and prevent opportunistic infections. For more information, see the Network's Simple Fact Sheet on combination therapy.

It's very important to stick to the correct 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, e.g., on an empty or full stomach. Also find out about side effects, and whether there are things you can do to help manage them. The Network has separate Simple Fact Sheets on each of the approved protease inhibitors: amprenavir (Agenerase), saquinavir (trade name Fortovase), ritonavir (Norvir), indinavir (Crixivan) and nelfinavir (Viracept).

Cautions: People with low T4 cell counts should be closely monitored when starting protease inhibitors. Possible infections such as MAC and CMV should be checked for using blood tests and eye exams. A group of French researchers recommend that anyone at risk for CMV gets an eye exam before starting a protease inhibitor. Repeat eye exams 15 days and one month after starting protease inhibitor treatment are then recommended.

There has also been 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. There have been 83 cases of this problem reported so far, usually 10-11 weeks after starting the protease inhibitor, although in one case symptoms started just four days afterwards.

Metabolic side effects. The latest side effects 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. 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. In a few cases, high levels of fats in the blood have caused heart problems because of fat in the coronary arteries. Coronary arteries carry blood to the heart, and blocked coronary arteries can cause heart attacks.

Many doctors now recommend you be given a 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 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 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.

For any person with HIV, a thorough medical check-up is a good idea before starting protease inhibitor treatment. 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.

Protease inhibitors can effect 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.

Newer protease inhibitors are being studied. VX-478/141W94 is a new protease inhibitor that is in clinical trials. For information on where clinical trials of experimental protease inhibitors are enrolling call The Network, (800) 734-7104.

For nutritional considerations see the APLA facts sheets. For a chart comparing protease inhibitors see Protease at a Glance - 1990 from the PWA Health Group.