HIV meds PK considerations

What are the food requirements of NRTIs?

None; all may be taken without food except didanosine

What are the mechanisms of NRTI metabolism, and how do they affect NRTIs’ drug interaction potential?

Oxidation and glucuronidation; causes less potential for drug interactions

What type of metabolism do NRTIs undergo?

Mostly renal

• Two exceptions: abacavir and TAF

Which NRTIs are the exceptions to the primary elimination route of NRTIs?

Abacavir, TAF

Do NRTIs require renal dose adjustment?

Yes, most of them do

Which NRTI is the exception to the renal dose adjustment that must be considered with NRTI use?

Abacavir

• TAF does require renal dose adjustment, but at a lower threshold than other NRTIs

Which NNRTIs must be taken with a high-calorie meal?

Rilpivirine, etravirine

Which NNRTIs can be taken without regard to food?

Doravirine

What type of metabolism do NNRTIs undergo?

Fecal

Etravirine induces:

CYP3A4

Etravirine inhibits:

CYP2C9, CYP2C19, and Pgp (weakly)

Which two ARVs are contraindicated with PPIs, and what classes are they?

Rilpivirine, NNRTI; atazanavir, PI

What are the food requirements of protease inhibitors?

Take with food for all

What type of elimination do PIs undergo?

Fecal

All PIs are substrates and inhibitors of the ___ and the ___

CYP3A4 enzyme, pgp efflux pump

Ritonavir is a substrate of which enzyme?

CYP2D6

Ritonavir is an inhibitor of which enzyme?

CYP2D6

All PIs are strong inhibitors of ___

CYP3A4

Which ARV drug class has an interaction with statins?

PIs

Which ARV drug class has an absolute contraindication with carbamazepine?

PIs

Which ARV drug class has an interaction with antiplatelets (e.g. clopidogrel)?

PIs

Which ARV drug class has an interaction with fluticasone (OTC)?

PIs

What are the food requirements of INSTIs?

Only elvitegravir/cobicistat should be taken with food

Which ARV drug class has decreased absorption when taken with polyvalent cations (Ca2+, Mg3+, Al, Fe; metals in OTC antacids)

INSTIs

What type of elimination do INSTIs undergo?

Fecal

All INSTIs are substrates of ___

UGT1A1 glucuronidation

What CYP enzyme interaction is clinically notable for INSTIs, which with INSTIs, and how do those INSTIs affect the CYP enzyme?

CYP3A4, elvitegravir and dolutegravir are its sustrates

Which ARV drug requires a max limit on metformin dose if the two are coadministered? What is the metformin max dose limit?

Dolutegravir (an INSTI); metformin max dose 1000 mg per day