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HIV 4/1/13 Flashcards

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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
What is a "long-term survivor"?
Survivors still alive after 10 years
26
What is an elite controller?
These pts remain symptom free, maintain low plasma virus levels and have normal CD4 counts without therapy after 10-15 years of infection
27
What do we think is related to elite controler status?
HLA B57 allele
28
What Mutation leads to a premature stop codon being introduced in the HIV genetic code?
DELTA 32 bp deletion in CCR5....homozygotes are resistant to the infection, heterozygotes show two year delay in progression.
29
So delta 32 del in CCR5 does what
Immature stop codon
30
Besides delta 32 CCR5, what other mutations can induce HIV resistance?
Nef deletions
31
What mutation in black africans makes them more susceptible to the infection>
DARC....however, it makes them resistant to malaria at the same time.
32
What are the two broad classes of HIV diagnostic tests?
Antibody detection, nucleic acid detection
33
Three types of ab detections tests
Rapid ab test using fluid, blood, or serum ELISA Western Blots
34
Three Nucleic acid detection tests
PCR RT-PCR bDNA
35
What is the ELISA assay that tests for circulating virus
p24 assay
36
ELISA must be confirmed by what>
WESTERN BLOT....this takes time, dipsticks are much better
37
What is the different between PCR and RT-PCR
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
What are the 4 processes which anti-retrovirals interfere with>
Reverse transcriptase Protease dependednt maturation Virus entry Integration
39
Two classes of RT inhibitors
Nukes and non nukes...nukes are nucleoside analogs. Non-nukes are not
40
What is the recomended regimen for anti-HIV therapy?
HAART: Two RT inhibitors and 1 Protease | inhibitor
41
Name the two fusion inhibitors
Enfuvirtide and Maraviroc
42
How does enfuvirtide work
Binds Gp41 (membrane fusion glycoprotein)
43
How is enfuvirtide administered?
Subcu
44
Does Enfuvirtide involve the CypP450 system?
Hell no
45
What are the major toxicities of Enfuvirtide?
injection site, hypersensitivity, Bacterial pneumonia
46
How does maraviroc work?
Binds CCR5 and prevents virus from entering the host cell.
47
Name the NRTI's
Didanosine, Lamivudine, Emtricibadine, Stavudine, Zidovudine, Abacavir (Did Lam Emt Sta Ab Zid
48
What is the major toxicity of zidovudine?
Bone marrow suppression....you should not give zidovudine with other drugs that are one marrow suppresants
49
What NRTI can cause hypersensitivity rxn due to genetic predisposition?
Abacavir
50
What should patients be screened for before starting Abacavir?
HLA-B 5701
51
Ethanol can increase the plasma levels of what NRTI?
Abacavir
52
What toxicities do all NRTIs cause?
GI distress and hepatic steatosis
53
Name the NNRTIs
Delavirdine, Nevirapine, Efavirenz
54
How do NNRTIs work?
They bind to a hydrophobic pocket of RT and induce conformational change to block the enzyme activity.
55
Do NNRTIs require intracellular phosphorylation?
No
56
What are the major toxicites of all NNRTIs
Maculopapular rash in extremities and trunk
57
Unique toxicities of Nevirapine and Efavirenz?
Navirapine causes hepatotoxicity | Efaverenz can cause neuropsychotic problems
58
What is teh Integrase inhibitor?
Raltegravir
59
Name the Protease inhibitors?
Inadenivir, Amprenavir, Nelfinavir, Sasquinavir, Sasquinavir, Lopinavir
60
How do protease inhibitors work?
Bind reversibly to protease action site and prevent polyprotein cleavage which inhibits maturation of virus
61
What are the common toxicitis of PI's?
Hyprelipidemia, Insulin resistance and diabetes, lipodystrophy, elevated liver function test, possible inc bleeding in hemophiliacs
62
Which must you drink water with to prevent allopecia, kidney stones, renal insufficiency
Indinavir
63
When do NRTI's develop higher affinity for viral reverse transcriptase than host DNA polymerase?
Once they are phophorylatd, NNRIs do not need to undergo phosphorylation for this
64
Trimethoprim-sulfamethoxazole significantly increases the plasma level of what drug
Lamivudine
65
Which class is metablozed by the CP450 system
NNRTIs and protease inhibitors

THE HIV (1 decks)

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