Lecture 14 - HIV

Question 1

What proteins are specific to HIV virus and not host cells

Answer 1

reverse transcriptase, AND MORE

Question 2

How does HIV replicate?

Answer 2

RNA is transcribed into DNA inside host cells using reverse transcriptase

Question 3

How does AZT work?

Answer 3

nucleside anologue that in viral infected cells get phosphorylated INTO dna chain and terminates it. (however also phosphorlyated in host cells but more selective to viral RT than host enzymes)

Question 4

What happened in the first trial of AZT in 1986

Answer 4

initial trial was discontinued as 18 placebo patients died and only 1 AZT patients died therefore considered unethical to continue knowing AZT sig decreased morbidity

Question 5

How long is AZT effective for and how does the timing of prescribing effect mortality

Answer 5

Therapeutic life of 6 months before resistance due to mutations. If you give to a patient early stages of disease their cd4 rises but when they eventually reach AIDs theyre already on AZT so die at the same time as patients who were on placebo ( as they’re given AZT when they reach AIDS ) = NO prolonged survival by prescribing early on

Question 6

How to NRTIs work?

Answer 6

drugs are phosphorylated by cellular kinases to become anologues of nucletides. then block RT from working and terminate proviral DNA synthesis.

Question 7

What are the side effects to NRTIs

Answer 7

lactic acidosis, hepatic steatosis, peripheral neuropathy, myopathy and lipoatrophy
» as inhibit activity of normal DNA polymerase.

Question 8

What is first line therapy for HIV in pregnant women

Answer 8

AZT

Question 9

what are ABC and TDF

Answer 9

now 1st choice NRTIs

Question 10

name two reasons why the more recent NRTIs have less side effects

Answer 10

minimal DNA polymerase inhibitory effects and no interactions with CYP enzyme complex

Question 11

Side effect of TDF NRTI?

Answer 11

nephrotoxic

Question 12

Why is resistance in HIV so common? How does it occur?

Answer 12

so many virus’ produced every day therefore many many mutations - if mutations occur in gene coding for viral RT then drug doesn’t bind to it as well as it used to.

Question 13

What are 3TC and FTC? what are they active against?

Answer 13

2nd generation NRTIs -form backbone of all cART - well tolerated and active against HIV and Hep B

Question 14

Why does increasing the number of HIV drugs prescribed increase the efficacy of treatment?

Answer 14

Less chance of virus forming mutations to all of them. AZT and 3TC is the backbone as have very different resistance profiles therefore more mutations need to occur for full resistance to develop

Question 15

How do NNRTIs work?

Answer 15

non- nucleotide analogue reverse transcriptase inhibitors

non competative inhibitors which induce a conformational change within RT

Question 16

why do NNRTIs have a high potential for drug drug interactions?

Answer 16

substrates of CYP enzyme

Question 17

what are NVP and EFV? when are they effective

Answer 17

1st generation NNRTIs, effective when used with 2 NRTIs

Question 18

side effects of EFV and NVP and why are they bad?

Answer 18

1) substrate of CYP enzymes therefore competitive to other toxins.
2) NVP = rash, SJS, hepatic necrosis
EFV = CNS side effects like vivid dreams and insomnia and hallucinations and depression

Question 19

How do protease inhibitors work?

Answer 19

HIV protease cleaves gag and gag pol polyproteins into components used for RT. PIs inhibit protease - virus particles still made but non infectious