2-22 Exam 13: Hiv Los

Front 1

1. Recognize the difference between primary immunodeficiencies and secondary immunodeficiencies

Back 1

Primary immunodeficiencies (genetic)
MANY genetic disorders- few to no treatments


Secondary immunodeficiencies (environmental: infection, malnutrition)

Front 2

2. Know that Adenosine Deaminase deficient SCID is treated with enzyme replacement therapy with ______.

Back 2

pegademase (Adagen).

Front 3

3. List the causes that can produce secondary immune depression.

Back 3

MPX are Very Cool Cats

1 Malnutrition
2 Viral infections
---Measles
---HIV => aquired immune deficiency syndrome (AIDS)
3 Parasitic infection (leprosy, malaria)
4 X-rays
5 cytotoxic drugs
6 corticosteroids

Front 4

4. List and describe the 6 major steps in HIV progression, in detail.

Describe the viral plasma levels, T-cell levels, and anti-HIV antibody levels at each of these steps (high, low, medium).

Back 4

exp - - -
vir H L L
ir/sero L M+ H
latent L H H
AIDS H M- M-
death H L L

AB/CD4 are the same except for during exposure (CD4=H) and possible during seroconversion where (CD4=H)

V = none, H, L, L, incr to H, H

1 Viral exposure with HIV through semen, vaginal fluids, milk (transmission rate up to 25%), or blood transfer

2 Acute viral infection

3 Strong immune response (seroconversion)

4 Clinical latency with progressive decline of immune cell numbers

Infection with opportunistic diseases (AIDS)

Front 5

5. Know the fluids through which HIV can be transmitted. Know that saliva has been determined to NOT be a vector.

Back 5

through semen, vaginal fluids, milk (transmission rate up to 25%), or blood transfer

Front 6

6. Recognize that HAART treatment within ____ of exposure leads to almost 100% non-infection.

Back 6

24 hrs

Front 7

7. Be able to explain, as to a patient, what seroconversion means, when it occurs, and why it is diagnostically relevant. (essay question)

Back 7

the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization

Front 8

8. Know the definition of AIDS is a T-cell count below __________ (in an HIV infected patient)

Back 8

<200 cells/mm^3

Front 9

9. Know the 3 basic parts of the viral structure of HIV, and recognize the basic functions of each part.

Back 9

Capsid - protein shell = protection fr digestion, attach prots
Envelope - (not all) lipoprotein envelope surrounding capsid
Nucleic acid - genetic information, most are single stranded RNA - uses reverse transcriptase

Front 10

10. Define retrovirus. Know the special viral enzyme necessary for retroviruses to replicate their RNA to DNA.

Back 10

A retrovirus is an RNA virus that is replicated in a host cell via the enzyme reverse transcriptase to produce DNA from its RNA genome.

Front 11

11. Describe the 4 growth steps for HIV. Know where CD4, GP120, CCR5 and GP41 proteins, reverse transcriptase, integrase and viral proteases fit into this scheme- be able to explain the function of each of these.

Back 11

Viral atachment and release of RNA into host – All the GP receptors: CD4, GP120, CCR5 and GP41

1 Reverse transcritption of viral RNA -> DNA – Reverse transcriptase

2 Insertion of viral DNA into host cell – Integrase

3 Production of viral mRNA; synthesis and clipping of viral proteins – viral proteases

4 Assembly and release of new viruses

GP120 binds CD4
GP120 attaches to CCR-5 or CXCR4
GP41 (viral) binds cell membrane to allow fusion

Front 12

12.a Understand the 6 sub-steps of HIV viral entry.

Back 12

a. HIV approaches T-cell presenting CD4 receptor

b. First viral GP120 binds CD4 receptor

c. Then GP120 attaches to Tcell’s chemokine receptor CCR-5 (R-5 viruses) or less commonly CXCR4 (X4 viruses)

d. Then viral GP41 can bind cell membrane

e. Conjunction of membranes allows membrane fusion

f. Viral core is inserted into cell

Front 13

12.b List the names and mechanism of action of viral entry inhibitor and ccr5 inhibitor drugs.

Recognize that these drugs do NOT have substantial cross-resistance with other drug classes.

Back 13

Fusion Inhibitors block GP41: enfuviritide (Fuzeon)

CCR5 antags block CCR5:
Maraviorc (Selzentry)

Front 14

13.a Understand the 4 sub-steps of reverse transcription and integration,

Back 14

a. Viral core uncoats

b. Viral RTase copies RNA to double stranded cDNA= ERROR PRONE= mutations!

c. cDNA translocates to nucleus

d. Viral Integrase inserts genome into host DNA

i. This is the template for viral replication

ii. ‘latent’ cells that don’t begin to replicate make it impossible to eradicate the virus from the body

Front 15

13.b know the name and mechanism of action of reverse transcriptase and integrase inhibitors.

Back 15

RTI's, 2 classes:
Nucleoside and Non-Nucleoside

Nuke:
abacavir (Ziagen)
lamivudine (Epivir)
tenofovir (Viread)
emtricitabine (Emtriva)
epzicom = abacavir + lamivudine
truvada= emtritabine + tenofovir

non-nuke:
efavirenz (Sustiva)
etravirine (Intelence)

Front 16

13.c Explain why RTIs don’t block cell division of our healthy cells as much as they block replication of HIV virus.

Back 16

we don't need/use RT since we replicate our DNA directly

Front 17

14.a Understand the 2 sub-steps of viral protein production and processing.

Back 17

a. Transcription & translation
mRNA and proteins are produced by host enzymes
New viral particles, new RNA
Inhibitors of apoptosis, etc

b. Proteins are processed
HIV protease cleaves polyproteins to functional proteins

Front 18

14.b Whose enzymes (host vs. virus) are used for transcription and translation.

Know whose enzymes are used for protein processing.

Know the name and mechanism of action of protease inhibitors,.

Back 18

RT: RNA to DNA (virus)
Integrase: viral DNA into host DNA
DNA Polymerase: xscribes prots from viral DNA (host)
Translation: host with protease provided by virus

Protease inhibitors inhibit the final step of xlation by preventing activation of pro-proteins

Front 19

15. Understand the 3 sub-steps of viral assembly and budding. Know that there are currently no approved drugs that act at this step of viral replication.

Back 19

a. Proteins and copied RNA translocate to the plasma membrane

b. Assemble

c. “Bud” or release from cell (free or into other cells)

Front 20

16. Understand what virologic nonresponder, and immunologic non-responder mean. You don’t need to know the statistics.

Back 20

Virologic nonresponders - Viral load doesn’t drop enough

Immunologic nonresponders - Viral load drops but CD4+ levels don’t rise = 5-27% of patients receiving HAART

Front 21

17. Describe HAART therapy, and recognize the 4 current ‘preferred’ drug combinations for drug naïve patients (by generic name for individual drugs, but also know the ingredients in the combos).

Back 21

HAART= “Highly active antiretroviral treatment” is our standard therapy.
HAART always uses 3 or more agents simultaneously

One of these (NNRTI/PI options)

a. efavirenz
b. atazanavir + ritonavir
c. darunavir + ritonavir
d. raltegravir

AND

a. tenofovir + emtricitabine

Front 22

18. Explain what a “trofile assay” tests for, and why it must be done before starting maraviroc.

Back 22

Trofile assay is to identify the tropism of an individual patient's HIV strain – R5, X4, or a combination of these known as dual/mixed (D/M). The results show whether the patient is infected with virus that enters cells using the R5 co-receptor, the X4 co-receptor, or both (dual/mixed).

Maraviroc is an entry inhibitor blocking CCR5. Because HIV can also use another coreceptor, CXCR4, an HIV tropism test such as a trofile assay must be performed to determine if the drug will be effective.

Front 23

19. Explain in a short answer what “boosting” is, why it is done (the effect on the other drug), and what drug is used to provide the boost.

Back 23

Adding RITINOVIR to inhibit P450
Reduces breakdown of protease inhibitors
Causes increase in other PI drug levels

Most common example:
“boosted lopinavir”= lopinavir + ritonavir (Kaletra)

Front 24

20. Recognize the drugs in “boosted lopinavir” or Kaletra, and in Atripla, Truvada, and Epzicom.

Back 24

Kaletra “boosted lopinavir” = lopinavir + ritonavir
Atripla = efavirenz + emtricitabine + tenofovir
Epzicom = abacavir + lamivudine
Truvada = tenofovir + emtricitabine

Front 25

21. Recognize the two general side effects of anti-HIV agents (be able to recognize the components of metabolic syndrome) In addition, recognize which drug class can cause mitochondrial toxicity.

Back 25

Metabolic syndrome
Lipodystrophy
changes in fat distribution,
fat loss in the face (sunken cheeks), arms and legs, buttocks;
Increase in fat in breasts, fat pad in the back of the neck (sometimes called buffalo hump); and gut (protease paunch).
Glucose intolerance/diabetes
CV disease- risk of MI is 2x with HAART trt.

Bone problems
osteonecrosis due to lack of blood supply to bone

Front 26

22. Recognize which anti-HIV agent requires an HLA test to avoid severe allergic reaction.

Back 26

(HLA)-B*5701 test before starting abacavir
5-8% of patients have HLAB*5701 allele: predisposes patient to abacavir systemic/organ type I hypersensitivity (does this mean anaphylaxis?)