Treatment Strategies For HIV Infection

Question 1

What cleaves the structural proteins of HIV into different components?

Answer 1

Protease

Question 2

What do protease blockers do?

Answer 2

Block protease activity preventing HIV from maturing to become infectious

Question 3

What blockers could you use to target HIV?

Answer 3

Reverse transcriptase blockers
Protease blockers

Question 4

What is NRTI mechanism of action?

Answer 4

In thymidine have OH group , used to add on next base
AZT - OH group is replaced by azide group
With inhibitor, modified base will come in and replace that base in the growing chain
There is no terminal OH group, so the chain can’t grow any longer
Chain terminates at this point

Question 5

What is AZT brand name?

Answer 5

Retrovir

Question 6

What is 3TC brand name?

Answer 6

Epivir

Question 7

What are epivir and retrovir?

Answer 7

Nucleos/tide RT inhibitors

Question 8

What do non-nucleoside RTIs (NNRTIs) do?

Answer 8

They inhibit RT enzyme itself

Question 9

How does nevirapine work?

Answer 9

Binds to a pocket near the RT active site and inactivates the enzyme

Question 10

What do protease inhibitors do?

Answer 10

Inhibit protease enzyme involved in maturation of HIV virion after it leaves the cell to make the full infectious virus

Question 11

What type of inhibitors are protease inhibitors?

Answer 11

Competitive enzyme inhibitors

Question 12

What does envelope protein of HIV bind to?

Answer 12

Receptor CD4

Question 13

What are HIV co receptors?

Answer 13

CCR5 or CXCR4

Question 14

What is R5 tropic?

Answer 14

Virus binds preferentially to CCR5

Question 15

What is the effect of entry inhibtors blocking co-receptors?

Answer 15

Don’t have immune dysfunction because the chemokines that bind to these receptors also bind to other receptors so knocking these out has minimal effect

Question 16

Why would blocking CD4 be an issue?

Answer 16

Because its bigger role immunologically

Question 17

What is an example of an integrase inhibitor?

Answer 17

Raltegravir

Question 18

What are integrase inhibitors?

Answer 18

Small molecule inhibitor targeting viral integrase enzyme, preventing integration of cDNA into host chromosome

Question 19

Why are people not cured of HIV using these drugs?

Answer 19

Because of anti retro viral resistance

Question 20

What is the issue with mono therapies?

Answer 20

Before treatment most virus is wild type but some virus has mutaitons that are resistant to different drugs
New drug works against WT but not certain species so that expands

Question 21

How can drug resistance be solved?

Answer 21

Multi-drug therapies?

Question 22

What is HAART?

Answer 22

Defined as treatment with at least three active anti-retroviral medications (ARV’s) - often called triple therapy

Question 23

When is HAART therapy commenced?

Answer 23

When blood CD4 count <350

Question 24

What does HAART typically contain?

Answer 24

Two nucleoside or nucleotide reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitor
Protease inhibitor

Question 25

What is the issue with HIV becoming latent?

Answer 25

No current way of getting HIV out the genome

Question 26

What is long term toxicity of HAART?

Answer 26

Hypercholesterolemia
Diabetes
Atherosclerotic cv disease
Lipodystrophy
Lactic acidosis
Osteoporosis

Question 27

What is dual therapy?

Answer 27

Instead of multi drug regimens can take 2 instead , this reduces side effects

E.g. dolutegravir and rilpivirine
Boosted atazanavir and lamivudine

Question 28

What is the future for HIV treatment?

Answer 28

CCR5 knockouts - if a cell doesn’t have it, it can’t be infected

Question 29

What is the natural mutation of CCR5 knockout?

Answer 29

Delta 32 mutation

Question 30

What is the irony for using genetic engineering for HIV CCR5 knockouts?

Answer 30

Some of the vectors are lentivirus vectors, so essentially using HIV against itself