Exam 4 - Stahelin INIs (study)

Question 1

Describe the mechanism by which bictegravir, dolutegravir, and elvitegravir inhibit HIV integrase.

Answer 1

2 steps occur when HIV DNA is being incorporated into host cell DNA. The 1st is the 3’-processing step, the 2nd is the strand transfer step. These drugs block the strand transfer step.

Question 2

Explain the key structural feature of the HIV integrase inhibitors that enables these drugs to inhibit HIV integrase.

Answer 2

Diketo acid (DKA)
-drugs mimic this to trick integrase into thinking they are this, which blocks activity of strand transfer

Question 3

INI drugs

Answer 3

bictegravir
dolutegravir
elvitegravir
raltegravir (not used currently)

Question 4

elvitegravir is coadministered with what drug? What does this drug do?

Answer 4

cobicistat, this drug inhibits CYP3A4, which boosts the levels of elvitegravir in pt serum

Question 5

Why does dolutegravir not need boosting?

Answer 5

It is not metabolized as fast by the CYP3A4 enzymes. half life is about 14h. Once daily dosing.

Question 6

Bictegravir considerations

Answer 6

-low resistance
-few drug interactions
-can be started without HLA-B*5701 testing
-cannot be used with rifampin
-raises SCr levels by about 0.1