Rachid P3 Final Paper.docx
AZT
- it was discovered in 1996 by WSU
- it was the first effective treatment against HIV
- it works by inhibiting reproduction of HIV
- it did not work in the long run but...
- it was the precursor to a more effective treatment
How does AZT work?
- AZT tricks HIV into thinking that this is a regular thymidine and HIV incorporates AZT into new DNA
- it cannot continue to make new DNA because HIV is no longer able to add more nucleotides
- due to the incorporation of the altered nucleotide
- two OH groups must be present to fuse two nucleotides (the smiley faces)
- AZT does not have the second required OH group
- it has a nitrogen group (N3) instead
- AZT does not allow replication to proceed
But why did AZT stop working?
- HIV has no proofreading abilities when it makes copies of itself
- this causes mutations and mutations lead to differences in HIV viruses
- eventually one of these variation will lead to a change that will allow HIV to be resistant to AZT
- this graph shows the effects of AZT on HIV viral loads in the blood
- notice how more and more AZT is needed to keep the viral load down
- this is because some HIV viruses have mutated and were able to ignore AZT
- eventually AZT will not longer work and viral loads will go back up
Research in HIV medicine
- scientists began to experiment with other ways to interrupt the HIV replication cycle
- by combining different drugs and treatments, you can lower the probability of HIV to evolve resistance
- if you incorporate 5 drugs, HIV must evolve to overcome all of those drugs at once
- if the HIV virion evolves resistance to drug number 2.. drugs 1, 3, 4, and 5 still work
- HIV viruses will still die
- for example: let’s say the probability of HIV to evolve resistance to AZT is 1/10
- introducing 4 other drugs that offer the same probability you get...
- (1/10)5 = 1/100,000
- combining drugs lowers the chances of a mutation occurring that will offer resistance to all 5 drugs
- with these promising numbers... HAART is developed
HAART (Highly Active Anti-Retroviral Therapy)
- it is a combination of treatments:
- reverse transcriptase inhibitor (such as AZT) - stops HIV replication
- protease inhibitor - prevents HIV protein production
- fusion inhibitor - blocks entry of HIV into healthy cell
- integrase inhibitor - blocks insertion of HIV DNA into healthy cell
AZT paved the road for the development of HAART
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