HIV

Question 1

What does HIV primarily infect?

Answer 1

CD4+ T cells

Question 2

HIV gp120 protein binds to what?

Answer 2

CD4 receptors

Question 3

What are the main HIV co-receptors?

Answer 3

CCR5

CXCR4

Question 4

What are the key stages of HIV replication?

Answer 4

1. gp120 binds CD4 receptor
2. Fusion of viral and host membrane
3. Uncoating of viral particle and release of viral material
4. Reverse transcrip of viral RNA into DNA
5. Import DNA into nucleus
6. Integration of viral DNA into host DNA
7. Transcrip of viral DNA to create new viral RNA
8. Export of new viral RNA
9. Translocation of viral RNA to create new viral protein
10. Assembly of new viral RNA and protein at cell surface
11. Budding of new viral particles
12. Release of new viral particles
13. Maturation of viral proteins

Question 5

What opportunistic infections are people with HIV susceptible to?

Answer 5

Candidiasis
Cytomegalovirus
Herpes simplex virus
TB
Mycobacterium avium complex

Question 6

What have most HIV drugs been developed against?

Answer 6

Reverse transcriptase

Protease

Question 7

What are the 6 targets for HIV drugs?

Answer 7

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
CCR5 antagonists

Question 8

What class drug is AZT?

Answer 8

NRTI

Question 9

How do NRTIs work?

Answer 9

Act as chain terminators at the substrate binding site of reverse transcriptase

Question 10

How do NNRTIs work?

Answer 10

Inhibit DNA repliation by binding at the allosteric non-bonding site of reverse transcriptase, causing a conformational change of the active site

Question 11

What are protease needed for?

Answer 11

In reproduction cycle, they are needed to process GAG and POL polyproteins into mature HIV components

Question 12

All approved protease inhibitors contain what bond instead of normal peptide bond?

Answer 12

Hydroxyethylene

Question 13

What class of drug is fuzeon?

Answer 13

Fusion inhibitor

Question 14

How does fusion work?

Answer 14

Blocks entry of HIV into cells. It mimics components of gp41 and displaces them, preventing normal fusion

Question 15

What is the mechanism of HIV fusion?

Answer 15

1. HIV approaches CD4+ T cell.
2. gp120 binds to CD4.
3. Conformational change, exposes gp41
4. gp41 composed of HR1 and HR2
5. Hydrophobic terminus of gp41 embeds into cell membrane.
6. HR2 begins to coil into grooves of HR1
7. Zipping destabolises both cell membranes and punches a hole
8. HIV capsid pass through and infection occurs

Question 16

What foes fuzeon mimic?

Answer 16

HR2 on gp41

Question 17

What does fuzeon bind to?

Answer 17

HR1

Question 18

What drug class in Maraviroc?

Answer 18

Entry inhibitor

Question 19

How does Maraviroc work?

Answer 19

Blocks the attachment of HIV gp120 t CCR5 receptor

Question 20

How do integrase inhibitors work?

Answer 20

Block integrase A and prevent the virus from adding its DNA into the DNA in CD4 cells.

Question 21

What does HAART stand for?

Answer 21

Highly active anti-retroviral therpy

Question 22

What does HAART do?

Answer 22

Generally takes 3 different antiretroviral drugs from at least 2 different classes

Question 23

What does HAART prevent

Answer 23

resistance

Question 24

What does HAART regimen comprise?

Answer 24

2 NRTIs

1 NNRTI, PI or II

Question 25

What are the new challenges to HAART?

Answer 25

Intolerance and long term toxicity.
Lack of adherence.
Co-morbidities.
Increasing drug resistance.

Question 26

What are fixed dose combinations?

Answer 26

Combinations of previous classes of HIV drugs in one pill