Anti-Retrovirals Part I

Question 1

What human cells do HIV cells enter and infect?

Answer 1

CD4 (aka helper T cells or T4 cells) –> immune cells that orchestrate immune response

Question 2

Describe how HIV enters human cells.

Answer 2

Binds to CD4 receptor and coreceptor to inject its viral RNA

Question 3

What are the two coreceptors that HIV uses to enter human cells.

Answer 3

R5 and X4 –> R5 is much more common in US (99%)

Question 4

Describe the steps of the HIV life cycle inside human cells after HIV RNA enters.

Answer 4

• Viral RNA is made into DNA via reverse transcription
• Viral DNA is integrated into the host cell DNA inside the host cell nucleus
• Virus integrated DNA make HIV pro-proteins
• The pro-proteins are cleaved and activated in the cell cytoplasm
• The activated HIV protein is packaged and departs the cell
• This departed protein restarts this process in a new healthy cell

Question 5

What is the enzyme that converts viral RNA to viral DNA?

Answer 5

Reverse Transcriptase

Question 6

What is the enzyme that allows viral DNA to enter the human cell nucleus and integrate with host DNA?

Answer 6

Integrase

Question 7

What is a pro-protein?

Answer 7

A protein that must be activated

Question 8

What is the enzyme that clips HIV proteins and activates them?

Answer 8

Protease

Question 9

What causes the death of host cells in HIV?

Answer 9

The CD4 cell realizes it has been infiltrated and undergoes apoptosis (cell death)

Question 10

Where in the HIV life cycle is the line between the window of opportunity for treatment and the point of no return?

Answer 10

Where viral DNA integrates with host DNA in the nucleus

Question 11

After exposure to HIV, how long is the window of opportunity for effective treatment?

Answer 11

48 - 72 hours –> Needle sticks must be treated within this time to prevent HIV

Question 12

What are the 7 points in the HIV life cycle where drugs could intervene? ID with an asterisk the points where current drugs act.

Answer 12

CD4 receptor *
R5 coreceptor *
X4 coreceptor
Reverse Transcriptase *
Integrase *
Protease *
Viral Departure

Question 13

Differentiate between HIV and AIDS.

Answer 13

HIV becomes AIDS when CD4 is or ever has been below 200 or the patient develops a serious opportunistic infection.

Question 14

What prophylaxis is given to HIV/AIDS patient with CD4 < 200 and why?

Answer 14

Bactrim to prevent PCP pneumonia

Question 15

Why is there no cure for HIV?

Answer 15

Some infected CD4 cells become HIV memory cells and stay in lymph nodes for years

Question 16

What class of HIV drugs are NRTIs and how do they work?

Answer 16

Nucleoside Reverse Transcriptase Inhibitors - drug inserts into growing DNA chain and prevents further growth.

Question 17

What antivirals work similarly to NRTIs?

Answer 17

Acyclovir and Valacyclovir

Question 18

What is the father of HIV drugs and what kind of drug is it?

Answer 18

AZT - Zidovudine (NRTI)

Question 19

How long after the first reported HIV case in the US was the first drug introduced?

Answer 19

6 years (1981 - 1987)

Question 20

What is the primary AE of AZT and what are the related S/S?

Answer 20

Anemia - tachycardia, fatigue, malaise

Question 21

List two NRTIs that have almost no AEs and state how they are administered.

Answer 21

Lamivudine (3TC) - BID

Emtricitabine (FTC) - QD

Question 22

Name an NRTI that has a high rate of causing anaphylaxis.

Answer 22

Abacavir

Question 23

What test must be done before giving a patient Abacavir?

Answer 23

HLA typing test to predict risk of anaphylaxis

Question 24

What is the clinical difference between Nucleotide RTIs and Nucleoside RTIs?

Answer 24

None - same mechanism with slightly different structure

Question 25

List two nucleotide RTIs.

Answer 25

``` Tenofovir (TDF) Tenofovir Alfenamide (TAF) ```

Question 26

Describe important clinical points about tenofovir (TDF).

Answer 26

Original version of the drug Effective against Hepatitis B Generic so low cost Contributes to renal failure --> CrCl must be > 60 ml/hr

Question 27

Describe important clinical points about tenofovir alfenamide (TAF).

Answer 27

``` New version of the drug Retains efficacy against Hepatitis B Not generic --> expensive Stays in cells where HIV replicates Less damaging to kidneys --> can use if CrCl > 30 ml/hr ```

Question 28

What is the mechanism of action of protease inhibitors.

Answer 28

Prevents clipping/activation of pro-proteins by inhibiting protease enzyme

Question 29

Name four protease inhibitors.

Answer 29

Tipranavir Atazanavir Ritonavir Darunavir

Question 30

Why is ritonavir not used at its full dose?

Answer 30

Causes too many GI AEs

Question 31

How is ritonavir used currently?

Answer 31

In very small doses because it is the most potent CP450 inhibitor. This allows other protease inhibitors to be given less frequently.

Question 32

What is the name for the method by which ritonavir is currently used?

Answer 32

It is used as a booster

Question 33

T/F: Ritonavir has many drug interactions.

Answer 33

T --> because it is such a potent CP 450 inhibitor

Question 34

What type of drug is Atazanavir and what drugs will it interact with and why?

Answer 34

Protease inhibitor that loves acid. It will interact with antacids - H2RAs (space) and PPIs (contraindicated)

Question 35

What is unique about darunavir?

Answer 35

It has a sulfa-moiety --> do not give to patients with severe sulfa allergies