HIV

Question 1

What is the MOA of NRTI?

Answer 1

inhibits HIV-1 reverse transcriptase by competitive inhibition of enzyme –> chain termination–> stops viral replication
*stop RNA to DNA

Question 2

What are the NRTI drugs?

Answer 2

Emtricitabine, Lamivudine, TDF, TAF, Abacavir

Question 3

What are the combo NRTI products?

Answer 3

Truvada- Emtricitabine/TDF
Descovy-Emtricitabine/TAF
Epzicom- Lamivudine/acabavir

Question 4

What is great about TAF (Vemlidy)?

Answer 4

better tolerated, better for renals and bone, FDA approved for HBV
-combo with Emtricitabine is great for HIV and HBV

Question 5

What is NRTI drug class side effects?

Answer 5

Lactic acidosis
hepatic steatosis
lipodystrophy -body fat accumulation
muscle aches
GI upset

Question 6

NRTI Drug specific side effects

Answer 6

Emtricitabine and Lamivudine
-HA, GI upset, rash

Abacavir

• fatal hypersensitivity rxn, need to check for HLA-B*5701
• if +, then cannot give abacavir
• rash and ↑ risk of MI (caution with older population)

TDF

• GI intolerance
• HA
• decreased bone mineral density and renal impairment (fanconi syndrome)
• associated with lower lipid levels than TAF

Question 7

What NRTI is effective against HBV?

Answer 7

all of them

Question 8

Pharmacokinetics of NRTI

Answer 8

renally excreted–> need renal dose adjustment

Abacavir-liver metabolism via alcohol dehydrogenase
-dont give to alcoholics

Question 9

What is the MOA of NNRTI?

Answer 9

inhibits RT by directly binding to it (non-competitive inhibition of RT

Question 10

What are NNRTI drugs?

Answer 10

Doravirine, Rilpovirine, Efavirenz

Question 11

Combo of NNRTI

Answer 11

2 NRTI + NNRTI

Delstrigo- doravirine/lamivudine/TDF
Complera-rilpivirine/emtricitabine/TDF
Atripla-efavirenz/emtricitabine/TDF
Odefsey-rilpivirine/emtricitabine/TAF

Question 12

NNRTI drug class effects

Answer 12

rash - TEN and SJS

liver toxicity

Question 13

NNRTI drug specific effects

Answer 13

Doravirine
-abnormal dream, abdominal pain, dizziness

Rilpivirine
-depression, insomnia, HA, rash

Enfavirenz

• zzzzz
• CNS effects=dizziness, drowsiness, sleepiness, insomnia, vivid dreams
• take at bed time with empty stomach
• neural tube defects in first trimester (terotogen)

Question 14

Pharmacokinetics NNRTI

Answer 14

Rilpivirine
-take with food

Enfavirenz
-take on empty stomach because of CNS side effects and CYP inducer

Question 15

Metabolism of NNRTI

Answer 15

liver metabolism via CYP 450 and substrate of CYP3A4

Efanirenz is substrate CYP2B6 –> genetic polymorphism (lower dose)

Question 16

DDI with NNRTI

Answer 16

NNRTI levels decrwase with Rifampin, Tegretol (carbamazaepine) and Dilantin (phenytoin)

Efavirenz decrease level
-rifampin, rifabutin, voriconazole, methadone, statins

Acid suppresive therapy decrease with Rilpivirine

• PPI contraindicated with rilpivirine
• H2 blockers: take 12 hrs before or 4 hrs after rilpivirine
• Antacids: take 2 hrs before or 4 hrs after

Question 17

DDI with NRTI

Answer 17

substrate of P-glycoprotein (TAF>TDF)

• do not give TAF with phenytoin, oxcarbazepine, phenobarbital, rifampin, rifabutin, rifapentine, St. John’s wort
• CYP inducer