Protease Inhibitors (PIs) for HIV

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Protease Inhibitors (PIs) for HIV


Generic NameBrand Name

Combination medicines

Generic NameBrand Name
lopinavir and ritonavirKaletra

Some of these medicines must be used with ritonavir.

How It Works

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

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

The combination of medicines used for ART will depend on your health, other conditions you might have (such as hepatitis), and results of testing. Talk to your doctor about the best treatment plan for you.

Medical experts recommend that people begin treatment for HIV as soon as they know that they are infected.1, 2 Treatment is especially important for pregnant women, people who have other infections (such as tuberculosis or hepatitis), and people who have symptoms of AIDS.

You may also want to start HIV treatment if your sex partner does not have HIV. Treatment of your HIV infection can help prevent the spread of HIV to your sex partner.3

The U.S. National Institutes of Health recommend one of the following programs for people who begin treatment for HIV:3

  • Efavirenz + tenofovir + emtricitabine
  • Ritonavir-boosted atazanavir + tenofovir + emtricitabine
  • Ritonavir-boosted darunavir + tenofovir + emtricitabine
  • Raltegravir + tenofovir + emtricitabine
Click here to view a Decision Point.HIV: When Should I Start Antiretroviral Medicines for HIV Infection?
Click here to view an Actionset.HIV: Taking Antiretroviral Medicines

How Well It Works

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:3

  • 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

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.

Here are some important things to think about:

  • Usually the benefits of the medicine are more important than any minor side effects.
  • Side effects may go away after you take the medicine for a while.
  • If side effects still bother you and you wonder if you should keep taking the medicine, call your doctor. He or she may be able to lower your dose or change your medicine. Do not suddenly quit taking your medicine unless your doctor tells you to.

Call 911 or other emergency services right away if you have:

  • Trouble breathing.
  • Swelling of your face, lips, tongue, or throat.

Call your doctor if you have:

  • Hives.

Common side effects of these medicines include:

  • An increase in blood sugar.
  • Changes in the distribution of body fat.
  • Headaches.
  • Nausea, diarrhea, and vomiting.
  • Rash.
  • An increase in cholesterol and triglycerides.
  • Liver problems, especially if you have liver disease.

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

Indinavir causes kidney stones in a small number of people who use it. The risk of kidney stones can be reduced by drinking at least 48 fl oz (1.4 L) of fluid each day.

Some protease inhibitors slightly increase the risk of having a heart attack.4

Side effects of any combination medicine can include the side effects of any of the single medicines in the combination.

Report all side effects to your doctor 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.

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

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

What To Think About

Food increases the absorption of atazanavir, nelfinavir, and darunavir.5 Certain acid-reducing medicines, such as omeprazole or famotidine, should not be taken at the same time as atazanavir. Before you take protease inhibitors (PIs), be sure to tell your doctor about any other medicines you are taking.

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

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.

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

Things to think about 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 how well these medicines work.

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.6

Taking medicine

Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.

There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.

Advice for women

If you are pregnant, breast-feeding, or planning to get pregnant, do not use any medicines unless your doctor tells you to. Some medicines can harm your baby. This includes prescription and over-the-counter medicines, vitamins, herbs, and supplements. And make sure that all your doctors know that you are pregnant, breast-feeding, or planning to get pregnant.


Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.

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



  1. U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents (2012). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available online:
  2. Thompson MA, et al. (2012). Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society—USA Panel. JAMA, 308(4): 387–402.
  3. U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents (2011). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available online:
  4. Lang S, et al. (2010). Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus–infected patients. Archives of Internal Medicine, 170(14): 1228–1238.
  5. Atazanavir (Reyataz) and emtricitabine (Emtriva) for HIV infection (2003). Medical Letter on Drugs and Therapeutics, 45(1169): 90-92.
  6. 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.


ByHealthwise Staff
Primary Medical ReviewerE. Gregory Thompson, MD - Internal Medicine
Specialist Medical ReviewerPeter Shalit, MD, PhD - Internal Medicine
Last RevisedApril 5, 2012

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