Protease inhibitors (PIs) for HIV

Examples

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Brand Name	Chemical Name
Reyataz	atazanavir

Brand Name	Chemical Name
Prezista	darunavir

Brand Name	Chemical Name
Lexiva	fosamprenavir

Brand Name	Chemical Name
Crixivan	indinavir

Brand Name	Chemical Name
Kaletra	lopinavir and ritonavir

Brand Name	Chemical Name
Viracept	nelfinavir

Brand Name	Chemical Name
Norvir	ritonavir

Brand Name	Chemical Name
Invirase	saquinavir

Brand Name	Chemical Name
Aptivus	tipranavir

Tipranavir (Aptivus) and darunavir (Prezista) must be used with ritonavir. They are only approved for people who have tried other antiretroviral medicines but did not improve.

How It Works

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Protease inhibitors (PIs) are antiretroviral medicines. They prevent HIV from multiplying, reducing the amount of virus in your body. When the amount of virus in the blood is kept at a minimum, the immune system has a chance to recover and grow stronger.

Why It Is Used

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The use of three or more antiretroviral medicines (highly active antiretroviral therapy, or HAART) is the usual treatment for HIV infection.

The preferred combination is two nucleoside reverse transcriptase inhibitors with one protease inhibitor (PI) or efavirenz (a nonnucleoside reverse transcriptase inhibitor, or NNRTI). Two-PI combinations are also used.

Treatment guidelines suggest the following for people with HIV:¹

• When considering treatment, experts currently consider your CD4+ cell count and the presence or absence of symptoms much more important than your viral load.
• If your CD4+ cell count is between 200 and 350 cells per microliter (µL), you should be discussing treatment with your doctor to avoid letting your CD4+ cell count drop below 200.
• If your CD4+ cell count is more than 350 cells per microliter, treatment may be offered if you have mild (non-AIDS) symptoms of HIV infection, such as weight loss, fevers, or frequent yeast infections.
• If treatment is not started, your condition will be monitored with frequent CD4+ cell counts.
• If you have symptoms of HIV or AIDS, you should consider starting treatment, whatever your CD4+ cell count is.

Should I start antiretroviral medicines for HIV infection even though I have no symptoms?

Taking antiretroviral medicines for HIV infection

After HIV has progressed to AIDS, treatment is recommended.¹

How Well It Works

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Combination therapy:

• Reduces viral loads, which can lead to stable or increased CD4+ cell counts, a sign that the immune system is still able to fight off opportunistic infections.
• Decreases the number and severity of opportunistic infections.
• Reduces or prevents the occurrence of resistance to the medicines.
• Prolongs life.

Antiretroviral therapy can also decrease symptoms of HIV infection, such as fever and weakness, and help the person gain weight.

The rate at which antiretrovirals decrease viral loads is affected by:¹

• CD4+ cell counts at the beginning of treatment.
• Viral load at the beginning of treatment.
• The dosage of the medicines.
• Whether the medicines are taken exactly as prescribed.
• Whether antiretroviral medicines have been taken before.
• Whether any opportunistic infections are present.

Side Effects

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To prevent serious medication interactions or a decrease in medicine effectiveness, it is important to learn which medicine should not be taken with PIs and other antiretroviral medicines.

PIs may cause:

• An increase in blood sugar.
• Redistribution of body fat.
• An increase in cholesterol and triglycerides.

In addition, each medicine may be associated with its own unique side effects.

Atazanavir (Reyataz)

Side effects of atazanavir include:

• Increased levels of bilirubin that can make the skin, nails, and whites of the eyes appear yellow.
• Abnormal heartbeat.
• Headaches.
• Pain or numbness in the arms and legs.
• Nausea, diarrhea, abdominal cramps.
• Rash.

Darunavir (Prezista)

Side effects of darunavir include:

• Diarrhea and nausea.
• Headaches.
• Rash.

Fosamprenavir (Lexiva)

Side effects of fosamprenavir include:

• Appetite loss.
• Headache.
• Diarrhea, nausea, and vomiting.
• Abnormal fat distribution on the body.

Indinavir (Crixivan)

Indinavir is relatively safe and has few side effects, which may include:

• Kidney stones, reported in 5% of people who use this medicine. The risk of kidney stones can be reduced by drinking at least of fluid each day.
• Mild stomach problems.
• Dry skin and lips.
• Loss of body hair.

Lopinavir and ritonavir (Kaletra)

Side effects of lopinavir and ritonavir include:

• Diarrhea.
• Fatigue.
• Headache.
• Nausea.
• Increased cholesterol and triglyceride levels, which may require treatment.
• Pancreatitis (rare).

Nelfinavir (Viracept)

Nelfinavir's most common side effect is diarrhea, which may be severe. Diarrhea can usually be controlled with nonprescription medicine such as loperamide (for example, Imodium AD or Kaopectate) or calcium supplements, such as Tums.

Ritonavir (Norvir)

Ritonavir has the most severe side effects, although these can be reduced if the first doses are small and increased gradually. Side effects may include:

• Diarrhea.
• Nausea or vomiting.
• Loss of appetite.
• Headache.
• Fatigue or weakness.
• Tingling around the mouth.
• Changes in the way foods taste.

Saquinavir (Invirase)

Saquinavir has few side effects, which may include:

• Diarrhea.
• Nausea.
• Abdominal pain.
• Rash.

Tipranavir (Aptivus)

Side effects of tipranavir include:

• Diarrhea, nausea, and vomiting.
• Belly pain.
• Headaches.
• Tiredness.
• Liver problems, especially if you have liver disease.

Report all side effects to your health professional at your next visit. He or she can adjust your dose or give you other medicines to reduce side effects. Some mild side effects, such as nausea, improve as your body adjusts to the medicine.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

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Because all protease inhibitors (PIs) were approved under the U.S. Food and Drug Administration's (FDA) accelerated approval process, the long-term safety of these medicines is not known.

Many people think antiretroviral medicines always have severe side effects. In fact, only a few people experience severe or dangerous side effects.

Food increases the absorption of atazanavir (Reyataz), nelfinavir (Viracept), and darunavir (Prezista). ² Certain acid-reducing medicines, such as Prilosec or Pepcid, should not be taken at the same time as Reyataz. Be sure to tell your doctor about any other medicines you are taking before taking protease inhibitors.

Resistance to PIs develops more frequently if these medicines are used alone or are not taken exactly as prescribed.

Ritonavir has negative interactions with many other medicines. Provide your health professional with a complete list of prescription and nonprescription medicines you are taking before you start taking ritonavir.

Lopinavir is combined with a low dose of ritonavir to inhibit the breakdown of lopinavir in the body. This delayed breakdown of lopinavir increases its effectiveness.

Lopinavir and ritonavir (Kaletra) and most other PIs can cause a rise in cholesterol and triglyceride levels, increasing the risk of pancreatitis.

PIs are expensive. They can cost up to 2 times more than nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs).

Factors to consider when choosing a combination of medicines include:

• The ability of the medicines to reduce your viral load.
• The likelihood the virus will develop resistance to a certain class of medicine. If you have already been treated with a certain antiretroviral medicine, you may already know whether you are resistant to medicines in that class.
• Side effects and your willingness to tolerate them.
• The cost of treatment.

Do not use the nonprescription herbal supplement St. John's wort while you are taking a protease inhibitor because St. John's wort can interfere with the effectiveness of these medicines.

Talk to your doctor about whether you can eat grapefruit or drink grapefruit juice while you are taking protease inhibitors. It may increase the side effects of some of these medicines.³

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.

References

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Citations

1. U.S. Department of Health and Human Services (2006). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Adult and Adolescent Guidelines. Available online: http://www.aidsinfo.nih.gov/guidelines.

2. Atazanavir (Reyataz) and emtricitabine (Emtriva) for HIV infection (2003). Medical Letter on Drugs and Therapeutics, 45(1169): 90-92.

3. Tatro DS (2004, January). Keeping up: Interactions of herbal supplements and grapefruit juice with medications used to treat HIV infection. Drug Facts and Comparisons News: 3–5.

Credits

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Author	Maria G. Essig, MS, ELS
Editor	Susan Van Houten, RN, BSN, MBA
Associate Editor	Pat Truman
Primary Medical Reviewer	Adam Husney, MD - Family Medicine
Specialist Medical Reviewer	Peter Shalit, MD, PhD - Internal Medicine
Last Updated	June 6, 2007