II. Mechanism

  1. Prevent HIV from being assembled
  2. Prevent release from infected CD4+ Cells

III. Protocols

  1. Most Protease Inhibitors are "boosted" with concurrent use of Ritonavir (Norvir)
    1. Limited by adverse gastrointestinal effects

IV. Preparations- suffix '/r' added when combined with Ritonavir

  1. Amprenavir (Agenerase)
  2. Atazanavir (Reyataz, ATV or ATV/r)
    1. Unboosted (without Ritonavir) has least adverse effect on lipids
  3. Darunavir (DRV or DRV/r)
    1. Less adverse effects on lipid profile
  4. Fosamprenavir (Lexiva, FPV or FPV/r)
  5. Indinavir (Crixivan)
  6. Lopinavir with Ritonavir (Kaletra, LPV/r)
  7. Nelfinavir (Viracept)
  8. Ritonavir (Norvir, /r)
  9. Saquinavir (Fortovase)
  10. Saquinavir mesylate (Invirase)
  11. Tipranavir (Aptivus)

V. Precautions

  1. Saquinavir and Saquinavir mesylate are not equivalent

VI. Adverse Effects

  1. See each individual agent for specific adverse effects
    1. Nephrolithiasis (Indinavir)
    2. Severe Diarrhea (Nelfinavir)
  2. Gastrointestinal upset
  3. Lipodystrophy
  4. Insulin Resistance
    1. Manage with lifestyle changes (diet, Exercise)
    2. Consider medications
      1. Thiazolidinediones (eg Rosiglitazone, Pioglitazone)
      2. Glucophage
  5. Severe lipid abnormalities
    1. Effects
      1. Hypertriglyceridemia
      2. Low HDL
    2. Management
      1. Consider Atazanavir (unboosted or boosted) or boosted Darunavir (DRV)
      2. Can be treated with Pravastatin (see below)
      3. Resolves with discontinuation of Protease Inhibitor
  6. Hepatotoxicity
    1. Associated with concurrent use of other HIV agents
    2. Associated with comorbid Hepatitis C
  7. Osteopenia

VII. Drug Interactions

  1. Drug Interactions are common
    1. Protease Inhibitors cause the most Drug Interactions of all Antiretrovirals
  2. Statin drugs (used for PI-induced lipid abnormalities)
    1. Pravastatin is first choice Statin for use with PI
    2. Rosuvastatin (Crestor) or Atorvastatin (Lipitor) may also be used with caution
    3. Do not use Simvastatin or Lovastatin with PI
  3. Apixiban or Rivaroxaban
    1. Metabolized by CYP3A4 and P-Glycoprotein
    2. Protease Inhibitors strongly inhibit CYP3A4 or P-Glycoprotein, with associated bleeding risk

VIII. Monitoring

  1. Fasting lipid panel with Glucose every 3-6 months

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