Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Antimicrobial Therapy and Prophylaxis (2023) > HIV > Flashcards

HIV Flashcards

1
Q

Brief timeline of HIV

A

1981: first cases
1983: discovery of retrovirus
1985: first blood test
1987: first drug
1995: first HAART
2020: estimated 75million have been infected, 36.3million associated deaths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Which cells are targeted by HIV?

A
  • vital cells of the immune system:
    • CD4+ T cells
    • macrophages
    • DCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name the mechanisms that lead to low levels of CD4+ T cells

A
  • pyroptosis of abortively infected T cells
  • apoptosis of uninfected bystander cells
  • direct killing of infected cells by lysis
  • killing of infected cells by CD8+ lymphocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

HIV biology

A
  • retrovirus
  • (+)ssRNA, enveloped
  • upon entry genome is reverse transcribed and integrated into host DNA -> provirus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HIV glycoprotein envelope

A
  • trimer with glycine shield
  • 1990 first broadly neutralising ABs (bnAB) was identified
  • 2008 single B cell analysis identified numerous bnABs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is special about the HIV envelope?

A

very few spike proteins

reasons:
- to limit transmission?
- prevent bivalves AB binding?
- delay induction of potent neutralising ABs?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Is there a vaccine?

A

No
There where trials in 1987/92/98 & 2003

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name the possible targets for HIV-drugs

A
  • fusion inhibitor
  • CCR5 inhibitors
  • integrase inhibitors
  • RT inhibitors
  • protease inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What did the introduction of HAART change?

A
  • 1995 introduced
  • AIDS-related death decline
  • # of HIV infected people still rising
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name the six classes of antiretroviral drugs used in HAART

A
  1. nucleoside-analogue reverse transcriptase inhibitors (NRTI)
  2. NNRTI
  3. integrase inhibitors
  4. protease inhibitors
  5. fusion inhibitors
  6. coreceptor antagonists

resistances for all classes observed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

HIV-1 RT

A
  • ~50 molecules per infectious virion
  • cellular t-RNA(lys3) molecule functions as primer
  • (+)ssRNA is converted into dsDNA (in vitro capsid is needed; mutation in palindromic initiation signal stops it)
  • no proof reading
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

RT inhibitors (NTRI)

A
  • analogues of natural nucleosides that lack 3‘-OH -> also inhibit cellular polymerase
  • used in low dose in combination therapy

resistances:
1. reduced affinity to drug
2. stimulate excision of incorporated analogue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

RT inhibitors (NNRTI)

A
  • bind to allosteric hydrophobic pocket -> changes conformation of active site
  • allosteric pocket not as conserved
  • 6 approved NNRTIs -> important in HAART
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does the HIV integrase work?

A
  • palindromic integration at conserved 3‘-OH AC
    -> cleavage adjacent to invariable dinucleotide d(C-A)
  • 2 distinct activities:
    1. 3‘-processing
    2. DNA strand transfer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Integrase strand transfer inhibitors

A
  • raltegravir was first (2007)
  • elvitegravir allows once-daily usage
  • dolutegravir exhibits higher genetic barrier to resistance development
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

HIV protease

A
  • cleaves gag- and gag-pol-encoded polyproteins (cleavage in extracellular virion)
  • important for maturation of virus
  • 2 identical peptide chains
  • flap movement between open and closed (substrate or inhibitor bound) form
17
Q

Protease inhibitors

A
  • saquinarvir was first in 1995
  • resistances:
    1. mutations leading to drug resistance
    2. compensatory mutations
18
Q

What is rionavir used for?

A
  • boosts the bioavailability of other protease inhibitors
  • is strong inhibitor of cytochrome P450 (drug metabilization)
  • important part of combination therapy
19
Q

CCR5 anatagonists

A
  • bind to allosteric hydrophobic pocket -> prohibiting co-receptor function
  • some carry single aa mutation in CCR5 and are resistant to HIV
  • maraviroc can cause severe side effects (life threatening)
20
Q

Fusion inhibitors

A
  • interfere with the collapse of fusion proteins
    • very conserved region (6 alpha-helix bundle)
  • enfuvirtide/fusion inhibitor T20:
    • binds to heptane repeat region of gp41
    • blocks formation of postausganges conformation of gp41
    • approved but two s.c. injections per day needed
21
Q

HIV cure?

A

a) mark cells with provirus and kill via CTL -> CTL escape mutations
b) CCR5 knockout -> impractical in broad population
c) provirus mutation and excision -> must be cell specific, potential risk of long-term expression of recombinase and nuclease, off-target effects

22
Q

What about bnABs?

A
  • > 20 ongoing trails
  • bnABs should block infection of new cells or/and induce death of infected cells

Antimicrobial Therapy and Prophylaxis (2023) (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions