Lecture 15 - HIV Biomedical Prevention, Possible Cures Flashcards Preview

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Flashcards in Lecture 15 - HIV Biomedical Prevention, Possible Cures Deck (43):
1

Behavioural ways to prevent HIV
1)
2)
3)

1) Education
2) Testing
3) Condoms

2

Biological ways to prevent HIV
1)
2)
3)
4)

1) Vaccine
2) Microbicides
3) Antiretroviral therapy
4) Treat sexually-transmitted infections (increase risk of transmission)

3

PREP

Pre-exposure phrophylaxis

Treat with cART before exposure to HIV

4

Possible vaccine approaches
1)
2)
3)
4)
5)
6)
7)

1) Recombinant proteins
2) DNA vaccines
3) Live vector vaccines
4) Live attenuated
5) Prime boost
6) Broadly-neutralising antibodies
7) CMV vectors

5

HIV recombinant protein vaccine

Good antibody response, no T cell response
Provides no protection

6

HIV DNA vaccines

Good T cell response, poor antibody response

7

HIV live-vector vaccines

1) Non-replicating poxvirus vector provides good T cell activation
2) Ad5 vector used in STEP trial. Might have increased risk of disease

8

Problems with live attenuated HIV vaccine

Potentially unsafe
Could revert to virulence

9

What is a prime boost vaccine?

DNA vaccine + protein or vector

10

Possible pro of CMV vaccine

Constant antigen presentation

11

Example of a prime boost vaccine

ALVAC + gp120

Provided 30% protection

12

Example of a DNA prime + recombinant Ad5 boost vaccine

1) DNA vaccine for gag, env, nef, pol at weeks 0, 4, 8
2) rAd5 boost of gag, pol, env at week 24

Not effective

13

When do broadly neutralising antibodies normally appear?

1-2 years into infection

At this point in infection, don't help patient

14

Leukophoresis

Isolates T cells

15

Immune response elicited by CMV vectors
1)
2)
3)

1) Unconventional MHCII-restricted CD8+ response
2) Breadth of epitope recognition
3) Promiscuity

16

How much does male circumcision protect against HIV infection?

70%

17

How does male circumcision decrease HIV infection rate?

Langerhans cells in foreskin are absent

Langerhans cells are what bring HIV into lymph nodes

18

Microbicide that can protect against HIV infection

Tenofovir

19

Tenofovir

Nucleoside reverse transcriptase inhibitor

20

BAT24 gel

Contains tenofovir

Applied 24 hours before sex, 24 hours after sex

21

Efficacy of tenofovir

30% reduction in female transmission

22

Antivirals given as PREP

Tenofovir
Truvada

23

PREP

Give tenofovir, truvada daily to uninfected, but at risk of infection

24

PREP efficacy

Oral truvada decreased transmission among gay men by 40%, up to 70% if compliance was high

25

Does treatment with HAART decrease chance of transmission?

Yes
97% reduction in discordant couples

26

Discordant couple

One partner HIV+, one partner HIV-

27

Most effective means of preventing transmission

ART treatment

28

Two different models of HIV cure

1) Cure - Complete absence of HIV-infected cells
2) Remission - Undetectable level of HIV with cessation of ART

29

Sterilising HIV cure

A complete cure

<1 HIV RNA copy/mL

30

Functional HIV cure

Remission of HIV

<50 HIV RNA copy/mL

31

Proof of possibility of cure
1)
2)

1) Berlin patient - Cured after receiving bone marrow transplant from a naturally-resistant donor

2) Mississippi baby - Born to HIV+ mother, given ART within 30 hours of birth. Cleared infection

32

Reasons for viral resurgence after ART stopped
1)
2)
3)

1) Latently-infected T cells
2) Residual viral replication
3) Anatomical reservoirs

33

HIV latency

In resting T cells, HIV proteins not expressed
When T cell is activated, HIV replication begins, other cells infected

Latent cells are very long-lived (EG: macrophages, memory T cells) and always infectious

34

Estimated number of latently-infected T cells in a patient controlling HIV with ART

~60/million T cells infected

35

Latent reservoir of cells

Naive, transitional memory, central memory T cells

36

Residual replication

ART can't prevent all HIV replication
Replication continues at a low level

37

Anatomical reservoirs

Brain, testes, gut, lymph nodes

38

Cells in anatomical reservoirs in which HIV resides

Macrophages
Astrocytes
Dendritic cells

39

Possible way to eliminate infected cells
1)
2)

1) Activate latently-infected cells
2) This makes cells display virus-infection markers, will be destroyed by immune system

40

Candidate for activating latently-infected cells

Histone deacetylase inhibitors

Promote transcription of all genes, including HIV genes --> Turn HIV genes on

41

Possible anti-HIV gene therapies
1)
2)
3)
4)

1) RNA interference --> block action of HIV genome
2) Express an anti-viral factor --> Mutant APOBEC3G
3) Remove an essential host factor --> CCR5
4) Block LTR of integrated HIV

42

Way to eliminate CCR5 expression

Zinc-finger nuclease heterodimer

Cuts part of CCR5, inactivates it

43

Possible application of gene therapy
1)
2)
3)
4)

1) Take blood, isolate T cells with leukophoresis
2) Remove CCR5 from T cells with zinc-finger nucelase
3) Reinfuse T cells
4) HIV will kill off CCR5+ cells, not CCR5- cells