HIV

Question 1

explain the HIV lifecycle

Answer 1

1. HIV attaches to CD4 cell
2. HIV enters CD4 cell
3. capsid enters the nucleus where HIV proteins/enzymes are released
4. reverse transcriptase makes a double stranded HIV DNA
5. integrase enables HIV DNA to join host cell DNA
6. protease cuts and assembles new HIV
7. each cell makes hundred of new HIV virons
8. CD4 cell will then die

Question 2

how do HIV cells bind to CD4 cells?

Answer 2

gp120 and gp41 receptor protein on the HIV cell binds to CD4 receptor and CCR5 co-receptors on the CD4 cell

Question 3

what are some HIV cell cycle drug targeting?

Answer 3

1. NRTIS/NNRTIS
2. attachment/entry inhibitors
   -monoclonal antibodies
   -attachment inhibitors
   -CCRS inhibitors
3. capsid inhibitors - intracellular and extracellular
4. integrase inhibitors -INIs
5. protease inhibitors
6. maturation inhibitors

Question 4

why is drug importance important?

Answer 4

1. lifelong treatment needed
2. resistance = limited future options
3. population of people w resistance
4. greater cost

Question 5

when does drug resistance occur?

Answer 5

found before starting treatment - at the time of infection

found during treatment during treatment interruptions -acquired

Question 6

how does drug resistance occur

Answer 6

random mutations during reverse transcriptase after changing environmental pressures

Question 7

what can change in environmental pressure

Answer 7

drug concentration

Question 8

how is drug resistance tested?

Answer 8

viral load needs to be >400 copies/mL
therefore blood supply must be amplified before testing

takes three weeks for results - give high barrier drugs

Question 9

what would you give when undergoing drug resistance tests?

Answer 9

high barrier drugs

Question 10

what are low barrier drugs?

Answer 10

single mutations = high level resistance

do not use in mono therapy
do not use in a regimen if they do not fully suppress viral therapy

Question 11

what are examples of low barrier drugs?

Answer 11

zidovudine
lamivudine
rilprivirine

Question 12

what are examples of high barrier drugs?

Answer 12

darunavir with ritonavir,
dolutegravir
bictegravir

Question 13

what are high barrier drugs?

Answer 13

develop resistance slowly even in mono therapy
single mutations = low level resistance
more forgiving drugs during non-adherence periods