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THE HIV > HIV 4/1/13 > Flashcards

HIV 4/1/13 Flashcards

1
Q

What are the 3 phases of HIV-1 disease progression?

A
  1. ) Acute Phase
  2. ) Asymptomatic latent phase
  3. ) Symptomatic phase
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2
Q

What occurs during acute phase

A

Rapid viral replication and dissemination throughout the bod

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3
Q

What occurs during asymptomatic phase?

A

Virus is brought under control by the immune system

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4
Q

What occurs during symptomatic phase

A

Immune failure, opportunistic infection, AIDS related cancer

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5
Q

What is the structure of HIV virions?

A

Spherical, enveloped

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6
Q

If a virion has an envelope, how must it enter the cell?

A

Must induce a membrane fusion event to dump the nucleocapsid into the cytoplasm.

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7
Q

What kind of genomic material does HIV contain

A

Two copies of the RNA genome (diploid)

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8
Q

WHat is p24?

A

A capsid protein that forms the cylindrical core. Used to test for HIV viral load.

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9
Q

Enzymes required for replication?

A

Reverse transcriptase, Integrase , protease

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10
Q

What are the envelope proteins

A

Gp120 (receptor binding), Gp41(Membrane fusion)

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11
Q

What are LTRs?

A

Long terminal repeats….basically promoters for mRNA synthesis and genome replication

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12
Q

What is Tat?

A

An accessory protein, unique to HIV that drives transcription

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13
Q

What is Rev

A

Another HIV unique accessory protein, drives mRNA transport out of the nucleus)

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14
Q

What is nef

A

yeah…accesory protein. contribute to virus pathogenesis….some pts who have HIV but dont progress to aids have nef mutants.

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15
Q

Describe virus attachment

A
  1. Gp120 binds CD4
  2. Gp 120 binds chemokine coreceptor
  3. This activates Gp41 (the fusion protein)
  4. Gp 41 promotes fusion and entry
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16
Q

What happens after entry

A
  1. RNA converted to DNA by reverse transcriptase

2. Integrase inserts a HIV DNA intertmediate into the host chromosome (this is now called a provirus)

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17
Q

HIV integration does not require——-

A

Cell division

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18
Q

Again, what does REV do?

A

Allows transport of unspliced RNA out of nucleus

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19
Q

How are virus particles released?

A

Budding…

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20
Q

What do protease inhibitors do?

A

Inhibit protease which is responsible for the cleavage of core proteins.

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21
Q

What drug can you use to drop the rate of prinatal transmission to 1%?

A

ZDV (AZT)

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22
Q

What level of T cell population signifies a shift from the chronic to symptomatic phase>

A

CD4 T cell below 200

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23
Q

The higher the viral load, the faster the progression of the disease

A

True

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24
Q

What is the typical survival rate once HIV infection has been diagnosed?

A

about 2 years with no anti-retroviral drug treatment

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25
Q

What is a “long-term survivor”?

A

Survivors still alive after 10 years

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26
Q

What is an elite controller?

A

These pts remain symptom free, maintain low plasma virus levels and have normal CD4 counts without therapy after 10-15 years of infection

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27
Q

What do we think is related to elite controler status?

A

HLA B57 allele

28
Q

What Mutation leads to a premature stop codon being introduced in the HIV genetic code?

A

DELTA 32 bp deletion in CCR5….homozygotes are resistant to the infection, heterozygotes show two year delay in progression.

29
Q

So delta 32 del in CCR5 does what

A

Immature stop codon

30
Q

Besides delta 32 CCR5, what other mutations can induce HIV resistance?

A

Nef deletions

31
Q

What mutation in black africans makes them more susceptible to the infection>

A

DARC….however, it makes them resistant to malaria at the same time.

32
Q

What are the two broad classes of HIV diagnostic tests?

A

Antibody detection, nucleic acid detection

33
Q

Three types of ab detections tests

A

Rapid ab test using fluid, blood, or serum
ELISA
Western Blots

34
Q

Three Nucleic acid detection tests

A

PCR
RT-PCR
bDNA

35
Q

What is the ELISA assay that tests for circulating virus

36
Q

ELISA must be confirmed by what>

A

WESTERN BLOT….this takes time, dipsticks are much better

37
Q

What is the different between PCR and RT-PCR

A

PCR can only recognize DNA copies so you must use reverse transcripase to get RNA to DNA.
RT-PCR can recognize RNA.
bDNA can also recognize RNA

38
Q

What are the 4 processes which anti-retrovirals interfere with>

A

Reverse transcriptase
Protease dependednt maturation
Virus entry
Integration

39
Q

Two classes of RT inhibitors

A

Nukes and non nukes…nukes are nucleoside analogs. Non-nukes are not

40
Q

What is the recomended regimen for anti-HIV therapy?

A

HAART: Two RT inhibitors and 1 Protease

inhibitor

41
Q

Name the two fusion inhibitors

A

Enfuvirtide and Maraviroc

42
Q

How does enfuvirtide work

A

Binds Gp41 (membrane fusion glycoprotein)

43
Q

How is enfuvirtide administered?

44
Q

Does Enfuvirtide involve the CypP450 system?

45
Q

What are the major toxicities of Enfuvirtide?

A

injection site, hypersensitivity, Bacterial pneumonia

46
Q

How does maraviroc work?

A

Binds CCR5 and prevents virus from entering the host cell.

47
Q

Name the NRTI’s

A

Didanosine, Lamivudine, Emtricibadine, Stavudine, Zidovudine, Abacavir (Did Lam Emt Sta Ab Zid

48
Q

What is the major toxicity of zidovudine?

A

Bone marrow suppression….you should not give zidovudine with other drugs that are one marrow suppresants

49
Q

What NRTI can cause hypersensitivity rxn due to genetic predisposition?

50
Q

What should patients be screened for before starting Abacavir?

A

HLA-B 5701

51
Q

Ethanol can increase the plasma levels of what NRTI?

52
Q

What toxicities do all NRTIs cause?

A

GI distress and hepatic steatosis

53
Q

Name the NNRTIs

A

Delavirdine, Nevirapine, Efavirenz

54
Q

How do NNRTIs work?

A

They bind to a hydrophobic pocket of RT and induce conformational change to block the enzyme activity.

55
Q

Do NNRTIs require intracellular phosphorylation?

56
Q

What are the major toxicites of all NNRTIs

A

Maculopapular rash in extremities and trunk

57
Q

Unique toxicities of Nevirapine and Efavirenz?

A

Navirapine causes hepatotoxicity

Efaverenz can cause neuropsychotic problems

58
Q

What is teh Integrase inhibitor?

A

Raltegravir

59
Q

Name the Protease inhibitors?

A

Inadenivir, Amprenavir, Nelfinavir, Sasquinavir, Sasquinavir, Lopinavir

60
Q

How do protease inhibitors work?

A

Bind reversibly to protease action site and prevent polyprotein cleavage which inhibits maturation of virus

61
Q

What are the common toxicitis of PI’s?

A

Hyprelipidemia, Insulin resistance and diabetes, lipodystrophy, elevated liver function test, possible inc bleeding in hemophiliacs

62
Q

Which must you drink water with to prevent allopecia, kidney stones, renal insufficiency

63
Q

When do NRTI’s develop higher affinity for viral reverse transcriptase than host DNA polymerase?

A

Once they are phophorylatd, NNRIs do not need to undergo phosphorylation for this

64
Q

Trimethoprim-sulfamethoxazole significantly increases the plasma level of what drug

A

Lamivudine

65
Q

Which class is metablozed by the CP450 system

A

NNRTIs and protease inhibitors

THE HIV (1 decks)

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