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Integrase Strand Transfer Inhibitor

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Integrase Strand Transfer Inhibitor, Integrase Inhibitor, Raltegravir, Isentress, InSTI, RAL, Bictegravir, Biktarvy, Dolutegravir, Tivacay, Cabotegravir, Vocabria, Cabenuva

  • Class
  1. Anti-retroviral agent
  2. Integrase Strand Transfer Inhibitor
  • Mechanism
  1. Integrase Strand Transfer Inhibitor prevents viral DNA from integrating into host DNA
    1. Blocks the integrase enzyme
  • Indications
  1. Anti-retroviral naive patients
  2. Anti-retroviral experienced patients
  • Preparations
  • Single Agents
  1. Bictegravir (Biktarvy)
  2. Dolutegravir (Tivacay)
  3. Cabotegravir (Vocabria)
    1. Available as oral agent, as well as monthly IM Injection (administered as part of Cabenuva)
  4. Raltegravir (Isentress)
    1. Dose: One 400 mg tablet orally twice daily
  1. Cabenuva combines Integrase Inhibitor and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
    1. Integrase Inhibitor: Cabotegravir
    2. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI): Rilpivirine)
  2. Dosing
    1. Two Intramuscular Injections in gluteal muscle (one for each drug) once monthly
    2. Administered in clinic, at $4000 per month
    3. Requires one month of oral "lead-in" daily therapy to evaluate tolerability before IM Injection
  3. Efficacy
    1. Appears as effective as triple therapy combinations
  4. Drug Interactions
    1. Less effective when combined with CYP 3A4 inducers (e.g. Phenytoin)
  5. References
    1. Orkin (2020) N Engl J Med 382(12):1124-35 [PubMed]
    2. Swindells (2020) N Engl J Med 382(12):1112-23 [PubMed]
    3. (2021) presc lett 28(3): 18
  • Efficacy
  1. Drug resistance is common
  • Adverse Effects
  • Raltegravir
  1. Diarrhea
  2. Nausea
  3. Headache
  4. Serum Creatinine phosphokinase (CPK) increases
  5. Mild Serum Creatinine increase without affecting Renal Function (Dolutegravir)
  6. Myopathy
  7. Rhabdomyolysis
  8. Insomnia
  • Drug Interactions
  1. Typically fewer Drug Interactions than other Anti-Retroviral Agents
  2. Phenytoin
  3. Rifampin
  4. St John's Wort
  5. Avoid taking at the same time as Calcium, Magnesium, aluminum and iron containing agents