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AZT and HAART (redirected from Ahmad - AZT and HART)

Page history last edited by Ahmad Rachid 11 years, 4 months ago

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 stands for azidothymidine (an artificially altered thymidine)

  • normal thymidine is an essential building block of DNA

 

                                   

 

  •   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:
    1. reverse transcriptase inhibitor (such as AZT) - stops HIV replication
    2. protease inhibitor - prevents HIV protein production
    3. fusion inhibitor - blocks entry of HIV into healthy cell
    4. integrase inhibitor - blocks insertion of HIV DNA into healthy cell

 

 

AZT paved the road for the development of HAART

 

 

 

 

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