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Pathology > I - HIV > Flashcards

I - HIV Flashcards

1
Q

How many people have AIDS worldwide

A

37 million

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2
Q

How many ppl have died of aids

A

39 million

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3
Q

How is HIV transmitted

A

Sexual
Infected blood
Vertical - mother to child

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4
Q

What type of virus is HIV

A

RNA retrovirus

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5
Q

What type of cell does HIV target as a host

A

Cd4 t helper cells mainly
Also cd4+ monocytes and dendritic cells

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6
Q

How does HIV replicate in host cell

A

Reverse transcriptase converts RNA to DNA to integrate in host genes

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7
Q

What is the receptor for HIV

A

Cd4 molecule

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8
Q

How does the virus bind to cd4+ cells (2 steps)

A

Gp120 - initial binding
Gp41 - conformational change

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9
Q

What coreceptors are used by hiv to bind to cd4 cells and on what cells are the found

A

Ccr5 and cxcr4 chemokine receptors (on macrophages)

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10
Q

What protein is the intrastructural support for HIV

A

Gag protein

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11
Q

Describe innate response to HIV

A

Activation of macrophages, nk cells and complement
Stimulation of dendritic cells via TLR
Release of cytokines and chemokines

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12
Q

Describe adaptive response to hiv

A

Neutralising & non neutralising ABs
Cd8+ T cells prevent HIV entry via chemokine production

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13
Q

Neutralising ABs to HIV

A

anti gp120 and anti gp41

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14
Q

Non neutralising AB to HIV

A

anti p24 gag IgG

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15
Q

What chemokines do cd8+ T cells produce to prevent hiv entry

A

Mip-1a
Mip-1b
RANTES

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16
Q

How does HIV damage the immune response

A

Activated infected cd4+ helper T cells are killed by cd8+ T cells / are anergised (disabled)
—> cd4 T cell memory lost and can’t activate memory cytotoxic T lymphs —> monocytes / dendritic cells not activated by cd4+ cells —> can’t prime naive cd8+ cyctoxic T lymphs

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17
Q

How does reverse transcriptase helps HIV evade immune response

A

It is error prone, so quasi species are produced which escape detection

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18
Q

Is HIV infectious when AB coated

A

YES

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19
Q

What are 2 key ingredients for effective HIV immunity

A

ABs to prevent infection and neutralise virus
Sufficient cytotoxic T lymphs to eliminate latent infected cells

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20
Q

Median time from HIV infection to AIDS

A

8 to 10 years

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21
Q

What is the median time from HIV infection to AIDS in rapid progressions

A

2-3 years

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22
Q

What are long term non progressors of HIV

A

Stable cd4 count and no symptoms after 10 years

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23
Q

% of HIV patients who are rapid progressors ? Long term non progressors ?

A

Rapid 10%
Long term non <5%

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24
Q

What predicts disease progression in HIV

A

initial viral burden

25
Q

How is HIV screened for

A

ELISA detects anti HIV ABs

26
Q

How is HIV diagnosed

A

Western blot to detect AB

27
Q

How long does it take after infection for a person to test positive for HIV via western blot & why

A

10 weeks
- western blot requires patient to have SEROCONVERTED (start to produce AB), which happens after 10 week incubation period

28
Q

How is viral load of HIV determined

A

PCR - detects viral RNA

29
Q

How is CD4 count determined

A

FACS - flow cytometry

30
Q

What is cd4 count used for in HIV Mx

A

Course of disease
Onset of AIDS (reduction in cd4 T cells)

31
Q

Define the cd4 count of aids

A

<200 cells / uL blood

32
Q

How is resistance to antiretrovirals tested

A

Phenotypic - viral replication is measured in cell cultures under increased concentrations of the drug then compared to wild type
Genotypic - mutations observed by sequencing of amplified HIV genome

33
Q

When should treatment be started after diagnosis of HIV

A

IMMEDIATELY (used to only be if Sx or low cd4)

34
Q

What is the mainstay of treatment for HIV & what does this consist of

A

HAART - highly active anti retroviral therapy
2 NRTIs (nucleoside reverse transcriptase inhibitors) and PI (protease inhibitor) (or NNRTI - nonNRTI)

35
Q

3 benefits of HAART

A

substantial control of viral replication
Increase in cd4 count
Decline in opportunistic infection and deaths

36
Q

Give an example of HAART regime

A

Emtricitabine + tenofovir + efavirenz
(Available as one pill - atripla)

37
Q

HAART regime in preg for mother & baby (drug, route & when)

A

Zidovudine
Antenatal PO, delivery IV
PO to baby for 6 weeks to reduce transmission

38
Q

Limitations of HAART (7)

A

doesn’t eradicate latent HIV
Doesn’t restore HIV specific T cell response
Toxicities
High pill burden / Adherence
Threat of drug resistance
QoL
Cost

39
Q

Describe HIV lifecycle

A

Attachment /entry
Reverse transcription and DNA synthesis
Integration to host DNA
Viral transcription
Viral protein synthesis
Assembly & budding

40
Q

Which part of HIV lifecycle do attachment / fusion inhibitors target

A

Attachment and entry

41
Q

Which part of HIV lifecycle do integrate inhibitors target

A

Integration to host DNA

42
Q

Which part of HIV lifecycle do protease inhibitors target

A

Assembly and budding

43
Q

Which part of HIV lifecycle do reverse transcriptase inhibitors target

A

Reverse transcription and DNA synth

44
Q

Which part of HIV lifecycle do NRTI / NNRTI target

A

DNA synthesis

45
Q

Example drug of fusion inhibitors

A

Enfuvirtide

46
Q

Side effects of fusion inhibitors

A

Injection reactions

47
Q

Drug example of attachment inhibitors

A

Maraviroc

48
Q

Examples of NRTIs

A

Zidovudine
Didanosine
Stavudine
Lamivudine
Zalcitabine
Abacavir
Emtricitabine
Epzicom
Combivir
Trizivir

49
Q

Side effects of NRTIs

A

Rare
Fever, GI issues

50
Q

Specific side effect of zalcitabine / stavudine

A

Peripheral neuropathy

51
Q

Which NRTI gives mitochondrial toxicity

A

Stavudine

52
Q

Side effect of abacavir

A

Hypersensitivity

53
Q

Example of nucleotide RTI

A

Tenofovir

54
Q

Side effect of tenofovir

A

Bone and renal toxicity

55
Q

Examples of NNRTIs

A

Nevirapine
Delavirdine
Efavirenz

56
Q

Side effects of NNRTIs

A

Hepatitis and rash
CNS effects

57
Q

Example of integration inhibitors

A

Raltegravir
Elvitegravir

58
Q

Examples of protease inhibitors

A

Indinavir
Nelfinavir
Ritonavir
Amprenavir
Fosamorenavir
Lopinavir
Atazanavir
Saquinavir

59
Q

Side effects of protease inhibitors

A

Hyperlipidaemia
Fat redistribution
T2DM

Pathology (87 decks)

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