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Antiretrovirals for HIV/AIDS - Protease inhibitors: Nursing Pharmacology



indinavir (Crixivan); nelfinavir (Viracept); atazanavir (Reyataz); fosamprenavir (Lexiva); tipranavir (Aptivus); darunavir (Prezista); saquinavir (Invirase), ritonavir (Norvir); ritonavir / lopinavir (Kaletra)
*High Alert Medications*

Protease inhibitors (PIs)
Inhibit HIV protease, preventing viral maturation
Treatment of HIV infection in combination with other antiretrovirals
  • Fatigue
  • Headache
  • Gastrointestinal side effects (e.g., diarrhea, nausea, vomiting)
  • Hypersensitivity reactions (e.g. skin rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis)
  • Insulin resistance, hyperglycemia
  • Hyperlipidemia
  • Hepatotoxicity
  • Cushingoid fat redistribution (peripheral wasting, truncal obesity, fat pad on the neck base)
  • Hemorrhage
  • Immune reconstitution syndrome
  • Indinavir, nelfinavir, ritonavir / lopinavir: nephrolithiasis
  • Nelfinavir: anxiety, depression, and suicidal ideation
  • Tipranavir (boxed warnings): intracranial hemorrhage, hepatotoxicity 
  • Saquinavir, atazanavir: prolonged QT interval
  • Saquinavir: photosensitivity
  • Hepatic and renal disease
  • Diabetes
  • Cardiac conduction disorders
  • Hemophilia
  • Coinfection by hepatitis B or C

Drug interactions:
  • Statins
  • Ergot derivatives
  • Rifampin
  • Current symptoms: fever, night sweats, diarrhea, fatigue, flu-like symptoms
  • Weight, vital signs, lymph nodes
  • Laboratory test results: CBC, renal and liver function, lipid panel, blood glucose, plasma HIV RNA level, CD4 count, antiretroviral medication resistance assay

  • HIV viral load, CD4 count 
  • Side effects 
  • Evaluate the therapeutic effects: suppression of viral replication, decreased HIV symptoms
  • General
    • Purpose of the medication: decrease HIV viral load 
    • Used in combination with other medications 
    • Administration 
      • Take once each day with food
      • If miss a dose, contact healthcare provider for directions 
    • Adhere to prescribed antiretroviral therapy
    • Medication does not completely eliminate virus from the body 
      • Can transmit virus to others
        • Inform sexual partners of diagnosis 
        • Use latex condoms 
  • Side effects
    • Nausea, vomiting, diarrhea 
      • Notify healthcare provider if becomes severe 
    • Notify healthcare provider
      • Hepatotoxicity 
      • Hyperglycemia 
        • Frequent blood glucose monitor with diabetes 
      • Fat redistribution

Antiretrovirals are medications used to treat infections caused by retroviruses. This is a group of RNA viruses that includes human immunodeficiency virus, or HIV, which can cause acquired immunodeficiency syndrome, or AIDS. Now, antiretrovirals include different classes of medications, among which some of the most commonly used are protease inhibitors.

Okay, so protease inhibitors, or PIs for short, are a class of antiretroviral medications with a characteristic suffix “-navir” in their drug names. Important protease inhibitors include indinavir, nelfinavir, saquinavir, atazanavir, fosamprenavir, tipranavir, darunavir, ritonavir, and a combination of ritonavir/lopinavir. All these medications are taken orally.

Once administered, protease inhibitors work by binding and inhibiting the viral enzyme HIV protease, which plays a major role in maturation of newly replicated viruses. The result is the formation of immature viruses, which are unable to continue infecting host cells.

Now common side effects associated with most protease inhibitors are fatigue, headache, and gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Protease inhibitors can also cause hypersensitivity reactions, such as skin rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, and sometimes anaphylaxis.

They can also cause metabolic issues, such as insulin resistance, hyperglycemia, as well as hyperlipidemia, and hepatotoxicity. Some protease inhibitors may also lead to cushingoid fat redistribution, which typically involves peripheral wasting, along with truncal obesity, and the development of a fat pad on the base of the neck.

Clients taking protease inhibitors may also develop serious side effects, such as hemorrhage, especially in clients with a preexisting bleeding disorder called hemophilia; as well as an excessive inflammatory response called immune reconstitution syndrome, that can also cause flare-ups of a previously known infection like tuberculosis.

Some individual protease inhibitor drugs can have additional specific side effects. Indinavir, nelfinavir, and the ritonavir/lopinavir combination may cause nephrolithiasis; while nelfinavir can cause anxiety, depression, and suicidal ideation. On the other hand, tipranavir has a boxed warning for intracranial hemorrhage and hepatotoxicity. Finally, clients taking saquinavir or atazanavir may present with a prolonged QT interval; while saquinavir may also cause photosensitivity.

Generally, protease inhibitors should also be used with caution in clients with hepatic and renal disease, as well as in those with diabetes, cardiac conduction disorders, and hemophilia. Caution should also be taken before administering protease inhibitors to clients with a coinfection by hepatitis B or C viruses.

Regarding interactions, protease inhibitors are potent inhibitors of the enzyme cytochrome P450 3A4, or CYP3A4 for short. As a result, protease inhibitors are contraindicated in combination with medications that are metabolized by CYP3A4, such as statins, ergot derivatives, and rifampin, which can lead to increased levels and toxicity.

Now, when administering a protease inhibitor like darunavir to a client with HIV as part of an antiretroviral regimen, begin your assessment by asking about their current symptoms, including fever, night sweats, diarrhea, fatigue, and other flu-like symptoms.