11.1 Antiretrovirals

Question 1

Which drug has an AE of hypersensitivity’ reaction (one or more of rash, GI,
malaise, respiratory distress).

Answer 1

Abacavir

Question 2

What is the MOA of NNRTI’s?

Answer 2

• Highly selective, noncompetitive inhibitors of HIV-1 RT
• Bind at a distinct site away from active site (NNRTI pocket)
• All NNRTI’s bind within the same pocket

• All result in inhibition of RNA- and DNA-dependent
DNA polymerase

• DO NOT REQUIRE PHOSPHORYLATION BY
CELLULAR ENZYMES

• Lack in vitro activity against HIV-2

Question 3

What are the disadvantages of NNRTI’s?

Answer 3

• Cross-resistance with NNRTIs
• Drug Interactions
• High incidence of hypersensitivity reactions (eg, rash)

Question 4

What are the adverse effects of NNRTI’s?

Answer 4

• Skin rash (including Stevens-Johnson syndrome)
• GI intolerance
• All are CYP3A4 substrates and can act as inducers, inhibitors or both of CYPs

Question 5

Which NNRTI induces CYP3A4?

Answer 5

Nevirapine

Question 6

Which NNRTI is teratogenic?

Answer 6

Delavirdine

Question 7

What is Etravirine metabolized by?

Answer 7

CYP 3A4, 2C9 and 2C19

Question 8

What are contraindications of Etravirine?

Answer 8

• CYP 3A4 inducer

* CYP 2C9 and 2C19 inhibitor

Question 9

What are the adverse effects of Etravirine?

Answer 9

• Rash (normally resolves within 1-2 weeks), nausea,
diarrhea
• Transaminase elevations (esp. in patients co-infected
with hepatitis)

Question 10

What is the current preferred NNRTI?

Answer 10

Efavirenz

Question 11

What are the most common AE with efavirenz?

Answer 11

• Mostly CNS (50%) (dizziness, headache, vivid dreams,

loss of concentration) – resolve after few weeks.

Question 12

What are the contraindications of Efavirenz?

Answer 12

• Potent inducer of CYP P450 enzymes.
• Pregnancy (D) (can be used after 1st trimester if
considered best choice)

Question 13

What is the MOA of Protease Inhibitors?

Answer 13

• Reversible inhibitors of HIV aspartyl protease (enzyme responsible for cleavage of viral polyprotein into RT, protease & integrase)
• Protease inhibition prevents virus maturation & results in production of non-infectious virions
• DO NOT REQUIRE INTRACELLULAR ACTIVATION
• Active against both HIV-1 and HIV-2

Question 14

What is important to know about the PK of Protease Inhibitors?

Answer 14

• Substrates for CYP 3A4

* Substrates for P-glycoprotein pump

Question 15

What are the adverse effects of Protease Inhibitors?

Answer 15

• Parathesias, nausea, vomiting, diarrhea

• Disturbances in lipid metabolism (diabetes,
hypertriglyceridemia, hypercholesterolemia)

• Chronic admin -> fat redistribution & accumulation
resulting in central obesity, dorsocervical fat enlargement, peripheral & facial wasting, breast enlargement and a
cushingoid appearance

• Atazanavir has less side effects than other PI’s