HIV integrase inhibitors

Mechanism of Action - Can't Get In

• HIV integrase is a key viral enzyme that covalently inserts viral DNA, synthesized by reverse transcriptase, into the host cell's chromosome. This step is essential for establishing a permanent, latent infection.
• Integrase Strand Transfer Inhibitors (INSTIs) are potent inhibitors that bind to the active site of the integrase enzyme, which requires divalent cations like $Mg^{2+}$ for its activity.
• This action blocks the crucial "strand transfer" step, preventing the viral DNA from being integrated into the host genome and halting replication.
• 📌 All INSTIs share the common suffix -tegravir (e.g., Raltegravir, Dolutegravir, Bictegravir).

⭐ Avoid co-administration with polyvalent cations (found in antacids, supplements). These agents chelate the drug, significantly decreasing absorption and efficacy. Dose INSTIs 2 hours before or 6 hours after cation-containing products.

The '-tegravirs' - Meet the Inhibitors

📌 Mnemonic: '-tegravir' integrates into "inTEGRAse" inhibitors.

Core agents include Raltegravir, Elvitegravir, Dolutegravir, and Bictegravir. They prevent viral DNA from integrating into the host cell chromosome.

Use & Adverse Effects - The Price of Power

• First-line therapy for most treatment-naive HIV patients due to high efficacy and favorable side effect profile.

• Common Class Side Effects:

  • Generally well-tolerated.
  • May cause GI distress (nausea, diarrhea), headache, and insomnia.

• Key Drug-Specific Adverse Effects:

  • Raltegravir: ↑ Creatine Kinase (CK), leading to myopathy and rare rhabdomyolysis.
  • Dolutegravir: ⚠️ Small risk of neural tube defects in fetus; avoid in early pregnancy or women trying to conceive. Can cause neuropsychiatric effects (insomnia, anxiety).
  • Elvitegravir: Requires boosting with cobicistat to inhibit its metabolism, increasing drug levels.

• Major Drug Interaction:

  • ⚠️ Avoid co-administration with polyvalent cations (e.g., $Ca^{2+}$, $Mg^{2+}$, $Fe^{2+}$, $Al^{3+}$) found in antacids and supplements. These agents chelate the integrase inhibitor, ↓ its absorption and efficacy.

⭐ High-Yield Fact: Always counsel patients to separate integrase inhibitor doses from antacids or supplements containing polyvalent cations by at least 2 hours before or 6 hours after drug administration.

• Mechanism of Action: Inhibit the HIV integrase enzyme, preventing the integration of viral DNA into the host cell genome.
• Nomenclature: All drugs in this class end with the suffix "-tegravir" (e.g., Raltegravir, Dolutegravir, Bictegravir).
• Clinical Use: A cornerstone of first-line antiretroviral therapy (ART) due to high efficacy and a high barrier to resistance.
• Key Side Effect: Can cause an increase in creatine kinase (CK).
• Drug Interactions: Chelation with polyvalent cations in antacids or supplements significantly reduces absorption.