SBL: HIV Pharmacology

Question 1

Why does Wolff say that emtricitabine, lamivudine, abacavir, and tenofovir are the NRTIs most used now?

Answer 1

They have a lower affinity for DNA Polymerase y

Question 2

This thymidine analog was the first antiretroviral drug discovered and is associated with bone marrow suppression, skeletal muscle myopathy, and hepatic steatosis

Answer 2

Zidovudine (AZT)

Question 3

This thymidine analog is most associated with peripheral neuropathy and lipodistrophy.

Answer 3

Stavudine (d4T)

Question 4

This cytosine analog can treat both HepB and HIV; monotherapy effective but is coformulated with tenofovir; and is associated with very little side effects besides prolonged use can cause hyperpigmentation in palms/soles

Answer 4

emtricitabine (FTC)

Question 5

This cytosine analog can treat both HepB and HIV, has a long intercellular half life. Least toxic antiretroviral agents.

Answer 5

Lamivudine (3TC)

Question 6

What is the dual treatment for HIV Naive patients?

Answer 6

Lamuvidine + Dolutegrevir

Question 7

Only guanosine analog that is not a cyp substrate.

Answer 7

Abacavir

Question 8

What HLA allele is abacavir associated with?

Answer 8

HLA-B 5701;

also avoided in those with coronary artery disease

Question 9

This nucleoTide can treat HBV, approved for 1x/day dosing, and can cause Fanconi Syndrome (ATN) and decreased bone mineral density.

Answer 9

Tenofovir disoproxil fumarate

Question 10

Which adenosine analog can cause peripheral neuropathy and pancreatitis?

Answer 10

didanosine

Question 11

This nucleoTide can treat HBV, approved for 1x/day dosing, and has a much lower plasma concentration but higher intracellular concentration=less toxic

Answer 11

Tenofovir Alfenamide

Question 12

This drug inhibits mRNA formation, has a unique mechanism of action as it remains resistant to mutations, and is very non-toxic but can see some immune reconstitution syndrome

Answer 12

Raltegravir

Question 13

This drug inhibits mRNA formation, has a high barrier to resistance, is metabolized by UGR1A1 (RENAL EXCRETION), and should be avoided in pregnancy.

Answer 13

Dolutegravir

Question 14

This INSTI inhibitor is given as a 1x/day fixed dose with cobicistat and emtricitibine as it is metabolized by CYP3A4 and needs to be boosted

Answer 14

Elvitegravir

Question 15

This INSTI inhibitor has high genetic barrier to resistance, and is only given as fixed dose single tablet regimen with emtricitibine/tenofovir alfenamide. Well tolerated

Answer 15

Bictegravir

Question 16

This protease inhibitor is no longer used due to pill burden, has poor bioavailability, and can cause GI distress and long term lipodistrophy

Answer 16

Saquinavir

Question 17

This protease inhibitor can cause nephrolitiasis

Answer 17

Indinavir=no longer used

Question 18

This protease inhibitor is a non-peptide that is the current first choice when boosted; only real side effect is it is a sulfa drug so can cause some hypersensitivity

Answer 18

Darunavir

Question 19

This PI is also a first choice when boosted, can see unconjugated hyperbilirubinemia with no hepatitis.

Answer 19

Atazanavir

Question 20

This PI can work after a lot of the others ones fail, is good when boosted, and can cause some GI distress with triglycerides and cholesterol increase

Answer 20

lopinavir

Question 21

The two drugs used to inhibit CYP3A4 are..

Answer 21

Ritonavir and Cobicistat

Question 22

Single exposure to what drug in absence of other drugs can cause resistance?

Answer 22

Nevirapine.. basically dont give by itself

Question 23

HIV can cause resistance to NNRTIs via?

Answer 23

A single aa substitution in a drug binding pocket

Question 24

This NNRTI can treat HIV1, induces Cyp3A4 so watch oral contriceptives and can cause itching as well?

Answer 24

Nevirapine

Question 25

NNRTI that is co-formulated with emtricibine and tenofovir, has CNS side effects (dizziness, concentration issues, vivid dreams) and was considered teratogenic but not anymore..

Answer 25

Efavirenz

Question 26

What is the first NNRTI approved for once daily dosing

Answer 26

Efavirenz

Question 27

This NNRTI is unique in that it still works after mutations affect others, long half life, causes fat distribution and immune constitution syndrome.

Answer 27

Etravirine

Question 28

This NNRTI is approved for treatment of Naive patients, and is not susceptible to mutations that render efavirenz and nevirapine. Excreted mostly in feces and has more adverse effects in children (depression, headache, decreased cortisol)

Answer 28

Rilpivirine

Question 29

This NNRTI is approved for treatment of Naive patients, has a novel resistance to mutations, so will work after others mutated and others will work after its mutated. Relatively low amounts of side effects.

Answer 29

Doravirine

New Best in class!!

Question 30

This 36aa peptide is not active against HIV 2 and must be administered parenterally.

Binds gp41

Answer 30

Efuvirtide (T-20)

Associated with challenge to adherence because its twice a day

Question 31

This drug binds CCR5, has an expensive test to determine tropism before can start. Is a CYP3A4 substrate and renal excreted. Generally well tolerated.

Answer 31

Maraviroc

Question 32

How does HIV become resistant to maraviroc?

Answer 32

If it has selectivity for CXCR4 then maraviroc will be not useful.