Treatment Strategies For HIV Infection Flashcards
What cleaves the structural proteins of HIV into different components?
Protease
What do protease blockers do?
Block protease activity preventing HIV from maturing to become infectious
What blockers could you use to target HIV?
Reverse transcriptase blockers
Protease blockers
What is NRTI mechanism of action?
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
What is AZT brand name?
Retrovir
What is 3TC brand name?
Epivir
What are epivir and retrovir?
Nucleos/tide RT inhibitors
What do non-nucleoside RTIs (NNRTIs) do?
They inhibit RT enzyme itself
How does nevirapine work?
Binds to a pocket near the RT active site and inactivates the enzyme
What do protease inhibitors do?
Inhibit protease enzyme involved in maturation of HIV virion after it leaves the cell to make the full infectious virus
What type of inhibitors are protease inhibitors?
Competitive enzyme inhibitors
What does envelope protein of HIV bind to?
Receptor CD4
What are HIV co receptors?
CCR5 or CXCR4
What is R5 tropic?
Virus binds preferentially to CCR5
What is the effect of entry inhibtors blocking co-receptors?
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
Why would blocking CD4 be an issue?
Because its bigger role immunologically
What is an example of an integrase inhibitor?
Raltegravir
What are integrase inhibitors?
Small molecule inhibitor targeting viral integrase enzyme, preventing integration of cDNA into host chromosome
Why are people not cured of HIV using these drugs?
Because of anti retro viral resistance
What is the issue with mono therapies?
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
How can drug resistance be solved?
Multi-drug therapies?
What is HAART?
Defined as treatment with at least three active anti-retroviral medications (ARV’s) - often called triple therapy
When is HAART therapy commenced?
When blood CD4 count <350
What does HAART typically contain?
Two nucleoside or nucleotide reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitor
Protease inhibitor
What is the issue with HIV becoming latent?
No current way of getting HIV out the genome
What is long term toxicity of HAART?
Hypercholesterolemia
Diabetes
Atherosclerotic cv disease
Lipodystrophy
Lactic acidosis
Osteoporosis
What is dual therapy?
Instead of multi drug regimens can take 2 instead , this reduces side effects
E.g. dolutegravir and rilpivirine
Boosted atazanavir and lamivudine
What is the future for HIV treatment?
CCR5 knockouts - if a cell doesn’t have it, it can’t be infected
What is the natural mutation of CCR5 knockout?
Delta 32 mutation
What is the irony for using genetic engineering for HIV CCR5 knockouts?
Some of the vectors are lentivirus vectors, so essentially using HIV against itself
