Antiretroviral Agents

Question 1

This step of HIV replication involves binding of HIV to receptors on the surface of CD4 T cells.

Answer 1

ENTRY

Question 2

This step in HIV replication involves the use of an enzyme to convert HIV RNA into DNA which then migrates to the host nucleus.

Answer 2

REVERSE TRANSCRIPTION

Question 3

This step in HIV Replication involves the use of an enzyme to insert viral DNA into host DNA

Answer 3

INTEGRATION VIA INTEGRASE

Question 4

This step in HIV replication involves creation of new viral rna

Answer 4

REPLICATION

Question 5

This step in HIV replication involves transformation into immature, noninfectious HIV particle or bud

Answer 5

ASSEMBLY

Question 6

This step in HIV replication involves cutting of the long HIV polyprotein chains into smaller functional HIV proteins to make mature infectious viral particle

Answer 6

BUDDING & MATURATION

Question 7

This drug class blocks entry of CCR5-tropic viruses into the CD4 T cell. Give the only approved drug in this class.

Answer 7

CCR5 Antagonists

Maraviroc

Question 8

Drugs in this class bind to envelope gp41 to prevent viral fusion to the CD4 T cell. Give the only approved drug of this class.

Answer 8

FUSION INHIBITORS

Enfuvirtide

Question 9

This drug class is known as the backbone of the ART regimens

Answer 9

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Question 10

What is the MOA of NRTIs?

Answer 10

Undergoes intracellular phosphorylation
Active triphosphate bunds to reverse transcriptase
DNA elongation is terminated after incorporation of NRTI triphosphate

Question 11

What 3 NRTIs should not be used as monotherapy for Hepatitis B? Why?

Answer 11

Lamivudine
Emtricitabine
Tenofovir

Risk of HBV resistance after prolonged use.
HBV flares after discontinuation

Question 12

What are the 2 ADR of NRTIs?

Answer 12

Mitochondrial toxicity which may present as peripheral neuropathy, pancreatitis, lipoatrophy, and hepatic steatosis.

Lactic acidosis syndrome

Question 13

NRTIs have drug to drug interactions with?

Answer 13

Rifampicin

It decreases the concentration of Tenofovir

Question 14

This NRTI is commonly combined with Emtricitabine.

If combined with Emtricitabine, considered as superior to other NRTI combi

Answer 14

Tenofivir Disoproxil Fumarate (TDF)

Question 15

This NRTI combi is effective in decreasing HIV transmission when administered as pre-exposure prophylaxis to HIV-uninfected patients

Answer 15

Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC)

Question 16

What are the main toxicities of Tenofovir Disoproxil Fumarate (TDF)?

Answer 16

Kidney Injury and Bone Loss

*do not give in px with GFR <60mL/min

Question 17

What is the NRTI approved for use in patients with GFR of less than/equal ti 30mL/min

Answer 17

Tenofovir Alafenamide (TAF)

Question 18

What are the 2 drugs that if combined with TAF, increases TAF levels?

Answer 18

Cobicistat or Ritonavir

Question 19

How do Cobicistat and Ritonavir increase TAF bioavailability?

Answer 19

They inhibit intestinal P-glycoprotein

Question 20

This NRTI in combination with Lamivudine is considered as first line NRTI combination for HIV

Answer 20

Abacavir

Question 21

Abacavir-lamivudine combination has the greatest efficacy if combined with?

Answer 21

Dolutegravir

Question 22

This NRTI is not given to patients with CAD because it increases risk for hyperlipidemia and vascular events

Answer 22

Abacavir

Question 23

These NRTIs should not be used in combination because they will compete for intracellular phosphorylation

Answer 23

Lamivudine & Emtricitabine

Question 24

What is the adr of lamivudine?

Answer 24

Pancreatitis. More severe in children

Question 25

What is the adr of Emtricitabine?

Answer 25

Skin changes: hyperpigmentation of palms and soles

Question 26

NNRTIs for tx-naive patients are?

Answer 26

Efavirens and Rilpivirine

Question 27

NNRTI for drug-resistant px is?

Answer 27

Etravirine

Question 28

What is the MOA of NNRTIs?

Answer 28

Prevents HIV-1 Reverse Transcriptase from adding new nucleotides to the growing DNA chain. Blocks cDNA elongation

Question 29

True or False: NNRTIs are active against both HIV-1 and HIV-2.

Answer 29

False. Only vs HIV-1

Question 30

What happens when an NNRTI-containing regimen is discontinued?

Answer 30

A period if functional NNRTI monotherapy may occur

Question 31

What happens in a Functional NNRTI Monotherapy?

Answer 31

This happens when an NNRTI-containing regimen is discontinued. NNRTI concentrations decline slower than other retrovirals. Therefor increasing the risk for NNRTI resistance

Question 32

What is the remedy for the Functional NNRTI Monotherapy?

Answer 32

Once an NNRTI-containing regimen is stopped, the concomitant nucleoside backbone should be continued for 3-7 days after the NNRTI is discontinued

Question 33

What are the adr of efavirenz and rilpivirine?

Answer 33

Neurologic and Psychologic

Question 34

This NNRTI is given at a dose of 600mg OD. High-fat/high-caloric meals increase absorption.

Answer 34

Efavirenz

Question 35

Why shouldn't Efavirenz be initiated in women who are likely to become pregnant or are in the 1st 8 weeks of pregnancy?

Answer 35

Potential risk for NTDs, facial clefts, and anopthalmia. But it can be used later in gestation

Question 36

What are the side effects of Efavirenz?

Answer 36

Cns toxicity, rash, hyperlipidemia, elevated hepatic transaminase

Question 37

What are the advantages of efavirenz combined with TDF/FTC?

Answer 37

Excellent potency Low pill burden Durability

Question 38

This NNRTI may be used in tx-naive px with a baseline viral load <100,000 copies/mL and a CD4 count of morethan or equal to 200 cells/microL.

Answer 38

Rilpivirine

Question 39

What are the side effects of Rilpivirine?

Answer 39

``` QT prolongation Depression Insomnia Headache Rash ```

Question 40

Rilpivirine must be administered with a meal and concimitant use of rilpivirine with ____________ & ___________ is contraindicated

Answer 40

PPI H2 antagonists Antacids

Question 41

Drug to drug interactions of rilpivirine

Answer 41

Rifampin, phenytoin, phenobarb, azoles, macrolides

Question 42

This is the most commonly used NNRTI for px with drug-resistant virus

Answer 42

Etravirine

Question 43

This drug class is an attractive option for px with either abn lipid profiles or risk factors for CAD since they have neutral effects on cholesterol & triglycerides

Answer 43

INSTI

Question 44

What is the MOA of Integrase Strand Transfer Inhibitors?

Answer 44

Target the strand transfer step of viral DNA integration | Prevent/inhibit the binding of the preintegration complex (PIC) to host cell DNA