HIV P. II

Question 1

How can anti-cancer drug AZIDOTHYMIDINE be effective in stopping HIV transcriptase?

Answer 1

Blocks conversion of viral RNA to DNA

Question 2

Name reverse transcriptase inhibitors that work well on reverse trancriptase?

Answer 2

NNRTI and NRTI

Question 3

Give a few examples of antiviral protease inhibitors (6 marks)

Answer 3

• HIV protease - drug target i.e. Saquinavir
  
  • blocks HIV fusing with T4 cell membrane
• Integrase inhibitors:
  
  • inhibit HIV integrase action
  • integration of DNA with chromosome is blocked i.e. Raltegravir entry inhibitors
• Entry inhibitors:
  
  • ​Bind CCR5 chemokine receptor
  • Blocks HIV entry
  • Maraviroc

Question 4

How do you get rapid evolution of drug resistance in HIV?

Answer 4

Viral genome recombination and error prone replication

Question 5

What is Pre-Exposure prophylaxis therapy?

Answer 5

• For people who don’t have HIV but are at high risk of getting it so take a pill a day to prevent it

Question 6

What drugs are used in PrEP?

Answer 6

• Combination drug of nucleotide reverse transcriptase inhbitor type (NRTI)
  
  • Emtricitabine & Tenofiver​

Question 7

What does antiretroviral therapy (ART) do?

Answer 7

Prevents resistance of HIV to the drugs and is the most potent means of killing the virus

Question 8

How many copies of the HIV RNA genome is required to be considered a slow or fast progression to AIDS?

Answer 8

• <4530 copies - clincally stable and slow progression to AIDS
• >36, 720 copies - rapid progression and early onset to AIDS

Question 9

What molecule decreases in concetration as viral copies increase?

Answer 9

CD4+ T helper cells

Question 10

Which viral load assay test is the most accurate:

a. HIV-1 RNA PCR
b. Branched DNA amplification
c. NASBA

Answer 10

b. Branched DNA amplification

c. NASBA

• both detect pol, BDA ~50 and NASBA ~400
• HIV-1 RNA PCR

Question 11

What is the best tool for phylogenetic clustering?

Answer 11

HIV full length genome sequence

Question 12

What is the hypothesis surrounding the Simian origin of HIV?

Answer 12

• HIV moved inot humans via bush meat trade and infected blood. After that was transmitted sexually

Question 13

What are some of the challenges faced for a cure?

(4 marks)

Answer 13

1. Site of infection - mucosal antiobdies not very effective for virus and can sit in a proviral state
2. Antibody response - less effective in neutralising antibodies
3. Latency
4. Sequence diversity

Question 14

Why has the vaccine design accelerated in recent years?

(3 marks)

Answer 14

• Rapid antigen discovery
• Novel vector platforms
• DNA/RNA vaccines

Question 15

What are ‘trispecific neutralising antibodies’? (3 marks)

Answer 15

• Use 2 sites = V1V2 and MPER to bind to HIV infected cells
• 3rd site of CD4 binding site recruits killer T-lymphocytes to eliminate virus
• A single molecule acts against all 3

Question 16

How are ‘Trispecific neutralising antibodies’ efficient as a vaccine?

Answer 16

• Engineered to target 3 antigens at once
• Cover 99% of all HIV types
• Protect against Simian/HIV able to get good protection

Question 17

What does HAART therapy stand for?

Answer 17

Highly Active Antiretrovrial Therapy

Question 18

How does HAART therapy work? (6 marks)

Answer 18

• Most frequently used treatment is 2 nucleoside analogue reverse transcriptase inhibitors combined with either protease inhibitor (efavirenz & atazanavir) or non-nucleoside reverse transcriptase inhibitor (tenoforvirio)
• Low dose of ritonavir added to protease inhibitor to prolong its action by inhibiting its breakdwon by CYP3A4 and simplifying its dose regimine
• As soon as resistance occurs shoudl change and add at least 2 drugs