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 (highly active antiretroviral therapy, or HAART) is the usual treatment for HIV infection.

The combination of medicines used for HAART 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.

Treatment guidelines suggest the following for people with HIV:1, 2, 3, 4

  • When considering treatment, experts currently consider your CD4+ cell count and the presence or absence of symptoms more important than your viral load.
  • If your CD4+ cell count is below 500 cells per microlitre (mcL), treatment is recommended to help keep your immune system healthy and prevent AIDS.
  • If your CD4+ cell count is greater than 500, you may want to consider treatment.
  • If treatment is not started, your condition will be monitored with frequent CD4+ cell counts.
  • If you have symptoms of HIV or AIDS, doctors recommend starting treatment, whatever your CD4+ cell count is.
  • If you are pregnant, you should be treated to prevent your unborn baby (fetus) from becoming infected with HIV.
  • If you also have hepatitis B and are starting treatment for it, you should begin treatment for HIV as well.

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, 4

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

Experts recommend one of the following programs for people who begin treatment for HIV:1, 3

  • Efavirenz + tenofovir + emtricitabine
  • Ritonavir-boosted atazanavir + tenofovir + emtricitabine
  • Ritonavir-boosted darunavir + tenofovir + emtricitabine
  • Raltegravir + tenofovir + emtricitabine

Some of the medicines listed above may not be used in some provinces. For information on which medicines are used in your province, talk with your doctor.

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: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

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.

PIs may cause:

  • 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.

Indinavir causes kidney stones in 5% of people who use it. The risk of kidney stones can be reduced by drinking at least 1.5 L (48 fl oz) of fluid each day.

Certain protease inhibitors (fosamprenavir, indinavir, and lopinavir/ritonavir) have been associated with a small increase in the risk of having a heart attack.

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.

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

What To Think About

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, 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 non-prescription 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

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 (2009). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available online:
  2. Hammer, Scott M, et al. (2008). Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society USA Panel. JAMA, 300 (5): 555–570.
  3. British Columbia Centre for Excellence in HIV/AIDS (2011). Therapeutic guidelines—Antiretroviral treatment (ARV) of adult HIV infection. Available online:
  4. 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:
  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.


By Healthwise Staff
Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine
Primary Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Specialist Medical Reviewer Peter Shalit, MD, PhD - Internal Medicine
Specialist Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Last Revised May 31, 2011

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