HIV DDI

What are substrates, inhibitors, and inducers?

• Substrate: drug BEING metabolized by an enzyme/is being transported

• Inhibitors: decrease ability of the enzyme to metabolize substrates; drug is NOT metabolized and can cause toxicities (too much drug)

• Inducers: increase amount/ability of enzyme to metabolize substrate; drug will LEAVE body faster (less drug so no intended effect)

Which meds are metabolized by CYP3A4?

• Statins

  • Atorvastatin

  • Simvastatin

  • Lovastatin

• PDE-5 Inhibitors

  • Sildenafil

  • Tadalafil

  • Vardenafil

• Anticoagulants

  • Apixaban

  • Dabigatran

  • Rivaroxaban

Which antiretrovirals are metabolized by CYP3A4?

• Integrase Inhibitors

  • Bictegravir

  • Dolutegravir

  • Elvitegravir

• NNRTIs

  • Efavirenz

  • Rilpivirine

  • Doravirine

• Protease Inhibitors

  • Darunavir

  • Atazanavir

  • Lopinavir

What is Rifampin contraindicated with?

• All Protease Inhibitors

What is known about ARVs and Acid suppressors DDI?

• Rilpivirine (Edurant)

  • Give 2 hrs before or 4 hrs after antacids

  • Give 4 hrs before or 12 hrs after H2RAs

  • C/I with PPIs

• Atazanavir (Reyataz)

  • Give 2 hours bfr or 1 hr after antacids

  • Give 10 or more hours after H2 blocker

  • GIve 12 hrs apart from PPI

What is known about Rilpivirne’s absorption?

• pH dependent so when given with PPI, the concentration decreases

What is known about INSTIs?

• They bind to Mg in the intgrase enzyme, and bind to cations in GI tract

Biktarvy can be taken at same time as supplements IF what?

• Taken together with food

Dolutegravir regimens can be taken how with supplements? What about Elvitegravir and Isentress?

• Dolutegravir → 2 hrs bfr or 6 hrs after

• Elvitegravir → separative by 4 hrs

• Isentress → 2 hrs from Fe supplements, 4 hrs from Ca + Mg supplements, NOT with CaCO3 antacids

What class inhibits the CYP3A4 substrates?

• Protease inhibitors → Darunavir/ritonavir, Darunavir/cobistat

What is the ineractions of Benzos and statins with the PI+cobi?

• Midazolam: CI with all PI and COBI

• Triazolam: CI will all PI and COBI

• Alprazolam, clonazepam, diazepam: start low dose and titrate up

  • Alt: lorazepam, oxazepam, temazepam (LOT)

• Sim+lovastatin → CI with all PI and cobi

  • Alt: Rosu+Ator+Prava+Pita

What is interactions of statins and PI+COBI?

• Pitavastatin+Pravastatin → no DDI

• Rosuvastatin → Do not exceed 10 mg ros with Atazanavir, no exceed 20 mg with Darunavir

• Atorvastatin → DNE 20 mg daily, wth Atazanavir NOT rec

• Lova+Siimva → NOT REC