Antiretroviral Agents

Question 1

If you get stuck with a needle that has been injected in a patient positive for HIV, what is the chance that you will undergo seroconversion?

Answer 1

3/1,000 or 0.33%

Question 2

What is considered the “backbone” of HIV antiretroviral therapy?

Answer 2

Two NRTIs and either (1) a protease inhibitor, (2) an NNRTI, or (3) an integrase inhibitor

Integrase inhibitors are the preferred first-line because they have few side effects and no documented resistance thus far.

Note: fusion inhibitors (enfurvitide) and CCR5 inhibitors are not recommended as first-line agents.

Question 3

What is the only fusion inhibitor?

Answer 3

Enfuvirtide (which inhibits gp41)

Question 4

Which class of HAART drugs is also active against HBV?

Answer 4

NRTIs (tenofovir)

Question 5

Efavirenz has a declining use due to its psychiatric and teratogenic effects, but it is useful in what patient population?

Answer 5

Those being treated with rifampin for TB because efavirenz does not induce CYP as much as nevirapine.

Question 6

Tenofovir should be avoided in which patients?

Answer 6

Those with osteoporosis or chronic kidney disease

Question 7

What are INSTIs?

Answer 7

Integrase strand inhibitors

Question 8

How is enfuvirtide administered?

Answer 8

Subcutaneous injection

Question 9

Which regimens are least likely to induce resistance?

Answer 9

2 NRTIs + either boosted PI or INSTIs

Note: the best is 2 NRTIs and an INSTIs

Question 10

The most absorbed form of tenofovir is __________.

Answer 10

TAF

Question 11

Why are NRTIs toxic against mitochondrial?

Answer 11

They inhibit mitochondrial DNA polymerase.

Question 12

Which class of HIV drugs is inhibited by PPIs?

Answer 12

NNRTIs (like rilpivirine or etravirine)

Question 13

What mechanism allows resistance to maraviroc?

Answer 13

If an HIV strain develops X4 tropism –in which it uses predominantly CXCR4 rather than CCR5.

Question 14

Why is maraviroc not in any combinations?

Answer 14

It is dosed twice daily, whereas most other antiretroviral drugs are once daily.

Question 15

HIV never enters a state of true ______________.

Answer 15

latency

Question 16

Resistance testing is recommended when ________________.

Answer 16

the patient is first seen and if their CD4 counts start to drop while on treatment

Question 17

How do NRTIs work?

Answer 17

They mimic nucleotides but lack the 3’ hydroxyl group necessary for elongation of the genome (like Sanger sequencing).

Question 18

How are the NRTIs administered?

Answer 18

Orally (most have good bioavailability)

Question 19

NRTIs are excreted renally with the exception of ______________.

Answer 19

abacavir and zidovudine

Question 20

The NNRTIs work by _________________.

Answer 20

inhibiting reverse transcriptase at a different, non-active site

Question 21

Which class of antiretroviral drugs is usually the most resistant to mutations that confer resistance?

Answer 21

Protease inhibitors

Question 22

What are some side effects of protease inhibitors?

Answer 22

Hyperlipidemia, hyperglycemia, and central adiposity (remember Guinevere with the raised candy and butter next to the fat horse with skinny legs)

Also, hepatotoxicity

Question 23

Describe how HIV tropism changes with disease progression.

Answer 23

HIV typically starts out with R5 tropism –meaning it targets cells with CCR5 –then progresses to X4 tropism.

Question 24

Tenofovir is contraindicated in patients with ______________.

Answer 24

osteoporosis and chronic kidney disease

Question 25

What is “boosting”?

Answer 25

Adding ritonavir to combinations to increase the serum concentration (because ritonavir is a potent inhibitor of CYP)

Question 26

Which of the entry-inhibiting drugs is hepatically metabolized?

Answer 26

Maraviroc

Enfuvirtide is metabolized by proteolysis so DDI with CYP is not a concern.