HIV Anti-viral Pharmacology (Fitz)

Question 1

Abacavir, Emtracitabine, Lamivudine, Tenofovir, and Zidovudine (prototype) are this class of drugs for HIV infx:

Answer 1

NRTIs –> these are 1st line

Question 2

Efavirenz (avoid in pregnancy) is first line preferred and Nevirapine and Etravirine are first line alternatives for this drug class in tx of HIV:

Answer 2

NNRTI’s

Question 3

Atazanavir and Darunavir (1st line), Ritonavir (adjunct), Lopinavir and Tipranavir and Fosamprenevir (alternate) are part of this class of drugs to tx HIV

Answer 3

PI’s

Question 4

Raltegravir is this type of drug to tx HIV

Answer 4

HIV integrase strand transfer inhibitor

Question 5

Maraviroc is this type of drug to tx HIV

Answer 5

CCR5 antagonist, Viral fusion/entry inhibitor

Question 6

Enfuvirtide is this type of drug to tx HIV

Answer 6

GP41 antagonist, viral fusion/entry inhibitor

Question 7

__ is the major factor contributing to tx failure in HIV

Answer 7

Drug resistance

Question 8

What is the MOA of NRTI’s?

Answer 8

Inhibition of HIV reverse transcriptase. Incorporate into viral DNA and terminate viral DNA synthesis

To thwart HIV replication host cell purine and pyrimidine kinase enzymes must convert NRTI’s into nucleotide triphosphates of HIV infected CD4 cells

Question 9

NRTI-TPs terminate viral DNA synthesis because they lack a __

Answer 9

3’-OH group

Question 10

What is the black box warning of all NRTIs?

Answer 10

Possibility of Lactic Acidosis syndrome, which is potentially fatal –> NRTI inhibits DNA polymerase gamma of mitochondria and impairs ox pho which leads to mt deficiency in proteins for ox pho

Also, features of hepatic dysfunction

Question 11

When should NRTI tx be suspended?

Answer 11

In setting of:

• rapidly rising aminotransferase levels
• progressive hepatomegaly
• metabolic acidosis of unknown cause

Question 12

What is a potential toxicity of Tenofovir? What should it be replaced with?

Answer 12

Risk of nephrotoxicity in pts w/ renal insufficiency

Abacavir is preferred since it is not associated with renal toxicity

Question 13

What is the HLA genotype that, if tested positive for, you should avoid Abacavir?

Answer 13

HLA-B*5701 –> ~6% pts are positive for genotype and want to avoid d/t hypersensitivity

Question 14

How are NRTIs eliminated?

Answer 14

Regally –> few clinically significant drug-drug interactions

Question 15

__ are the “backbone” in all regimens to control and treat HIV:

Answer 15

NRTIs

AVOID 3 NRTI COMBOS D/T ADDITIVE TOXICITY

Question 16

What is the DHHS recommendation for dual-NRTI pairs to tx the naive pt because of its overall potency, favorable toxicity profile, and convenient dosing?

Answer 16

Tenofovir/emtricitabine (TDF/FTC)

Question 17

This NRTI pair is preferred in pregnancy:

Answer 17

Zidovudine/Lamivudine

KNOW THIS!!!!!

Question 18

When is Efavirenz not the preferred NNRTI?

Answer 18

Not preferred in 1st trimester of pregnancy

Question 19

This NNRTI is for drug-resistant HIV strains

Answer 19

Etravirine

Question 20

What is the MOA of NNRTIs?

Answer 20

Bind and distort reverse transcriptase. Inhibited reverse transcriptase cannot make viral DNA

Question 21

What is a toxicity of NNRTIs?

Answer 21

All NNRTIs have been associated with rash and hypersensitivity-including Stevens Johnson syndrome (worse with Nevirapine)

Hepatotoxicity may be severe and life-threatening

Question 22

In regards to NNRTI resistance, most experts do not continue NNRTI meds in teh setting of __ mutation

Answer 22

K103N

Question 23

What is the current clinical use of NNRTIs?

Answer 23

In combo therapy together with 2 NRTIs

TDF/FTC/EFV (Aritripla)

Question 24

What are PIs used with for a “boosting” effect?

Answer 24

Ritonovir

Boosts bioavailability and PK of other protease inhibitors

Question 25

What is the MOA of PIs?

Answer 25

Mimic peptide bond betwen Phenylalanine and Proline at positions 167 and 168 of gag-pol polyprotein, which is the target of HIV aspartyl protease

Question 26

How are PIs metabolized?

Answer 26

Extensive hepatic metabolism –> poor bioavailability

Question 27

What does Ritonavir inhibit to boost levels of other PIs (ATV or LPV)?

Answer 27

CYP3A

Question 28

Darunavir, fosamprenavir, and tipranavir provoke this hypersensitivity:

Answer 28

Sulfonamide

Question 29

What are acute/short term adverse effects of PIs? Long-term?

Answer 29

Acute/short term: Hepatotoxic, Drug-drug interactions

Long: hyperlipidemia (increased visceral fat), lipodystrophy, insulin resistance

Question 30

What are current clinical use of PIs?

Answer 30

In combo therapy together with 2 NRTIs

Preferred: TDF/FTC PLUS ATV/Ritonavir or DRV/Ritonavir

Question 31

Describe what you should do for HIV post-exposure prophylaxis:

Answer 31

4 week tx with 2-3 drug regimen. Must be started ASAP-always within 3 days of a possible exposure

2 drug option: Tenofovir + Emtricitabine, once daily

3 drug option: The 2 above with the addition of Raltegravir

Question 32

What is the overall preferred regimen in HIV+ pregnant women?

Answer 32

2 NRTIs-Zidovudine/Lamivudine PLUS PIs-Lopinavir/ritonavir

Question 33

What is the MOA of Raltegravir?

Answer 33

HIV integrase inhibitor

Excellent tolerance and lack of impact on lipids

Question 34

What is the MOA of Maraviroc?

Answer 34

Blocks binding of HIV outer envelope protein gp120 to CCR5 chemokine receptor –> prevents downstream events

Question 35

What is the MOA of Enfuvirtide?

Answer 35

Inhibits gp41 fusion and entry

Question 36

What are adverse effects of Enfuvirtide?

Answer 36

Injection site rxns
Hypersensitivity rxns
Increased risk of bacterial pneumonia