HIV

Question 1

What is HAART?

Answer 1

Highly active anti-retroviral therapy - combination of 3 drugs.

• 2x nucleoside reverse transcriptase inhibitors
• 1x “other” class of antiviral

Question 2

What regulatory protein is required for HIV genome transcription?

Answer 2

Tat

Question 3

How does regulatory Rev contribute to spreading of the virus?

Answer 3

Rev regulates viral expression of intact genome and transported to the cytoplasm without being spliced.
(Rev’s it up…!)

Question 4

What is the host cellular defense that can prevent virus spread?

Answer 4

deoxycytidine deaminase, host protein that gets incorporated into virion and carried to new cell where it removes amines from the viral genome preventing its function.

Question 5

What are two of HIV’s “restriction factors” that overcome cellular defenses?

Answer 5

Vif - induces degradation of cytidine deaminase preventing it from being transfered with the virion.
Vpu - inhibits host cell from tethering the released virions.

Question 6

What co-receptor is required for M-trophic strains?

Answer 6

CCR5 Receptor, located on primary T-cells and Macrophages.

–Form that dominates in asymptomatic persons–

Question 7

How does T-tropic HIV differ from M-trophic?

Answer 7

T-trophic is primarily present during the AIDs phase of the disease and is associated with progression of the disease.
Binds the CXCR4 co-receptor.

Question 8

What kind of people have a very high resistance to infection with HIV?

Answer 8

Those with a CCR5 gene mutation - preventing expression of the receptor on the cell surface without any noticeable health changes.
–DRUG TARGET– binding CCR5 blocking virus access

Question 9

What virus virulence factor inhibits Tetherin?

Answer 9

Vpu

Question 10

What are the step in the fusion process?

Answer 10

First - binding of the CD4+ receptor, which causes conformational change exposing the co-receptor and fusion proteins.
Second - fusion proteins extend out from the virus complex binding to the membrane, unable to proceed until co-receptor is bound.
Third - Co-receptor CCR5 binds, fusion proteins “Snap” back onto virus complex completing the membrane fusino.

Question 11

What kind of drug was produced to prevent membrane fusion?

Answer 11

A peptide that mimics the “snapback” region of the virus binding to the extended fusion proteins, preventing their function. -Fuzeon-

Question 12

What location does virus infection/replication reside in the beginning of disease process?

Answer 12

Lymph Nodes, once high enough infection some spills into the blood since immune system prevents.

Question 13

Why does infection localize to the lymph nodes?

Answer 13

Since HIV usually penetrates mucosal surfaces and the resident DC cells recognize the foreign antigen and binds it, bringing it to the lymph node to be present to T-cells.
–DC cells facilitate the infection–

Question 14

Which trophism is most important for transferring of the virus?

Answer 14

M-Tropic, or R5

Question 15

What are the common ways in which T-cells are killed in HIV?

Answer 15

Directly - lysis by HIV, merging with uninfected cell, apoptosis
Indirectly - CD 8+ cells destroy the CD4+ infected cells

Question 16

What are the phases of an infection?

Answer 16

Acute Infection - steep increase in virus load, activates humoral and cytotoxic T-cell response.
- Virema is cleared by B/CD8 cells, but CD4 count continues to decline.
Late Stage - once CD4 count get too low, immune system failure - AIDS

Question 17

What is a classic sign indicating HIV?

Answer 17

Infection by opportunistic organisms.

Question 18

What are most common therapeutic targets?

Answer 18

• RT inhibitors
• Protease Inhibitor
• Fusion Inhibitor
• Entry Inhibitor
• Integrase inhibitor

Question 19

Who should get screen for HIV?

Answer 19

Anyone between 13-64 age
Pregnant patients
IV drug users
Commercial sex worker
At least 1 new sexual partner since last screening

Question 20

When do the first symptoms onset after exposure?

Answer 20

Symptoms first arise about 2-6 weeks after infection

Question 21

What are the common acute infection symptoms?

Answer 21

Viral Syndrome - Fever, Myalgias, Weight loss, RASH, lympadenopathy, fatigue, oral ulcers

Question 22

How can you diagnose HIV?

Answer 22

4-6 weeks after infection - ELISA Antibody testing
–after immune system mounts response - Cheap
Antigen Testing - p24 and HIV RNA - 10-14 days
Combined Antibody/Antigen - 3 weeks

Question 23

What is the recommendation for HIV treatment?

Answer 23

After starting treatment, should never discontinue, even if viral load becomes undetected.

Question 24

What is the goal of treatment?

Answer 24

To get viral load below levels of detection to prevent the chances of it spreading to others.

Question 25

What is the longevity of a patient who gets HIV treatment?

Answer 25

They can live a normal life just about as long as an uninfected person, as long as they stay on treatment.

Question 26

Can mothers pass HIV onto their children? If they are treated?

Answer 26

Yes - ~25% chance, but if they are treated it essentially becomes impossible.

Question 27

What factor determines rate of transmission?

Answer 27

Viral Load. Thus why Acute infection is most infectious.

Question 28

How can HIV be transferred?

Answer 28

Intercourse (vaginal/anal)
Needle Stick
Needle Sharing
Blood/Tissue - other body fluids (bad kind)

Question 29

What can NOT transfer HIV?

Answer 29

Feces
Nasal Secretions, Sputum, Saliva
Sweat
Vomit
Urine

Question 30

What factors go into increased chances of transfer to a healthcare worker?

Answer 30

• Deep tissue penetration
• Blood present on infected object
• Terminally ill patient (higher viral load)

Question 31

What kind of people should consider post exposure prophylaxis?

Answer 31

Anyone exposed to a known HIV+ individual or an unknown person (sexual assault).

Question 32

What is essential when starting the post exposure protocol?

Answer 32

Must start antiviral treatment within 72 hours!

Question 33

Who kind of patients would be eligible for Pre-Exposure prophylaxis?

Answer 33

High Risk individuals. People who come into contact with people with untreated HIV or live a high risk life style.
– Partner of someone with untreated HIV –
Must get re-tested every 3 months while on the treatment plan.