Protease Inhibitors



Protease Inhibitors are a class of drugs with drug names ending in the suffix,“navir”. These include Atazanavir, Darunavir, Indinavir, and Ritonavir. Protease inhibitors work by inhibiting HIV protease, preventing the viral enzyme from cleaving HIV proteins into functional units. By doing this, protease inhibitors prevent HIV replication, and can be used along with other antiretrovirals to treat HIV infections. However, protease inhibitors also have several adverse effects. Specifically, Ritonavir is a CYP enzyme inhibitor, which can lead to drug interactions with other drugs. Other side effects common to all protease inhibitors include Hyperglycemia, GI upset, and lipodystrophy, also known as  “Cushing-like syndrome”. Less common side effects seen more commonly with Indinavir are renal toxicity and thrombocytopenia. Lastly, Rifampin should not be taken to treat TB in patients who are also taking protease inhibitors, since rifampin is a potent CYP enzyme inducer -- these patients should take rifabutin instead.

Key Points

  • Protease Inhibitors
    • Drug Names (-navir ending)
      • Atazanavir
      • Darunavir
      • Indinavir
      • Lopinavir
      • Ritonavir
      • Saquinavir
      • Fosamprenavir
    • Mechanism
      • Inhibits retroviral protease
        • Encoded on pol gene, protease usually cleaves the polypeptide products of HIV mRNA into functional parts
        • Inhibition of proteases causes non-functional protein production and non-infectious viral progeny
    • Indications
      • HIV
        • Active against both HIV-1 and HIV-2
        • Component of highly-active antiretroviral therapy (HAART)
          • Usually 3 drugs: 2 NRTIs and integrase or protease inhibitor
    • Adverse Effects
      • Ritonavir: Inhibits CYP450 enzymes
        • May be used to increase (“boost”) other drug concentrations
      • Hyperglycemia
      • GI upset
      • Cushing-like syndrome (Lipodystrophy)
        • Redistribution and accumulation of visceral fat
      • Renal toxicity (indinavir)
        • Presents with nephropathy, hematuria
      • Thrombocytopenia (indinavir)
      • Avoid rifampin
        • Due to CYP450 induction, as most of these drugs are metabolized by CYP
        • Use rifabutin instead for TB