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MICR2222 - Medical Virology > L8 - HIV (4) > Flashcards

L8 - HIV (4) Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the 3 classes of drugs licensed for ‘STANDARD’ therapy?

A

NRTIs
NNRTIs
Protease inhibitors

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2
Q

What is HAART?

A

Highly active AntiRetroviral Therapy (HAART)

triple therapy

2 NRTIs + NNRT or PI

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3
Q

What happens if you stop taking HAART?

A

the virus will come back

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4
Q

Where do NRTIs target?

A

reverse transcription step

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5
Q

Where do NNRTIs target?

A

reverse transcription step

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6
Q

Where do PIs targets?

A

virion maturation after virion release

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7
Q

What are NRTIs?

A

Nucleoside analogue RT inhibitors

inhibit HIV reverse transcriptase

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8
Q

examples of NRTIs?

A

AZT - azidothymidine - analogue of thymidine

ddC- analogue of deoxycytidine

ddI - analogue of adenosine

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9
Q

What are problems with NRTIs?

A

toxicity

resistance

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10
Q

What disease was AZT first shown to inhibit?

A

MLV

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11
Q

What are NNRTIs?

A

Non-nucleoside RT inhibitors

target site - NOT ACTIVE SITE

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12
Q

examples of NNRTIs?

A

Efavirenz
Nevirapine
Etravirine
Delavirdine

ALL VERY DIFF STRUCTURES

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13
Q

Where does cleavage occur when HIV matures?

A

Cleavage of Gag and Gag-pol into individual peptides

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14
Q

Examples of PIs?

A

Saquinavir

Nelfinavir

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15
Q

What are pros of HAART?

A

avoids cross resistance

treatment interruptions to remove selective pressure

reduce viral load & disease progression

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16
Q

What are cons of HAART?

A

Cost

compliance

side effects

drug-drug interaction

post-therapy reversion

17
Q

What is an entry inhibitor for HIV?

A

Maraviroc

CCR5 antagonist

salvage therapy in patients with R5 virus

18
Q

What is T-20?

A

peptide based entry inhibitor - ENFUVIRTIDE

blocks conformational changed in fusion of viral-cellular membranes by gp41 fusion domain

19
Q

What is the clinical name for T-20?

A

Enfuvirtide (ENF)

Fuzeon

20
Q

How does Enfuvirtide work?

A

prevents membrane fusion by causing a block in the pre-hairpin intermediate

21
Q

What is integrase?

A

catalyses independent events

resulting in cleavage of host DNA, splicing of provirus into cleavage site

22
Q

What are the 3 domains of Integrase?

A

HHCC - zinc binding

Core - catalytic

DNA binding domain

23
Q

examples of inhibtors of integrase?

A

Raltegravir
Elvitegravir
Doltegravir

24
Q

What are problems in developing AIDS vaccine?

A

HIV genetic variability

Animal models

Clinical trials - Phase I/II and III

moral issues

25
Q

What are phase I/II clinical trials for?

A

safety & immunology

26
Q

What are phase III clinical trials for?

A

efficacy

27
Q

What are features of candidate AIDS vaccines?

A

envelope glycoprotein based

rarely induced CD8+ CTL responses - swerve towards antibody response, do not work very well

combination vaccine: prime-boost

28
Q

What is the combination vaccine: prime-boost?

A

prime - recombinant canarypox

boost - recombinant gp120

29
Q

What is AIDSVAX?

A

Bivalent vaccine

only stimulated humoral immunity

no effect on vaccinated vs. placebo

30
Q

What are some comments on the ‘AIDSVAX failure’?

A

worked better on Black/Asian participants

31
Q

What is RV144 vaccine?

A

prime - recombinant canarypox expressing gp120 (ALVAC)

boost - AIDSVAX recombinant gp120

barely any diff. between vaccinated and placebo

32
Q

How could RV144 be better if virus matched vaccine at certain aa positions?

A

efficacy improves to 48% or 78%!

33
Q

What are future thoughts for HIV therapy?

A

bnAbs - broadly neutralising antibodies

target conserved region of Env trimer

34
Q

What are challenges for the future thoughts of HIV therapy?

A

instable Env trimer

50% Env = glycan

sequence variation

MICR2222 - Medical Virology (13 decks)

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