IDMM Week 5 PBL

Question 1

replicative cycle of HIV

Answer 1

1. free virus
2. entry: virus binds to a CD4 molecule and one type of “co-receptor” (either CCR5 or CXCR4)–receptor molecules are common on the cell surface. The virus fuses with the cell
3. Penetration: virus empties contents into cell
4. Reverse transcription: single strands of viral RNA are used by the reverse transcriptase enzyme to create double stranded DNA
5. integration: viral DNA is inserted into the cell’s own DNA by the integrase enzyme
6. transcription: when the infected cell divides, the viral DNA is read and long chains of proteins are made
7. assembly: sets of viral protein chains come together
8. Budding: immature virus pushes out of the cells, taking some cell membrane with it. The protease enzyme starts processing the proteins in the newly formed virus
9. immature virus breaks free of the cell
10. maturation: the protease enzyme finishes cutting HIV protein chains into individual proteins that combine to make a new working virus

Question 2

what enzyme incorporates HIV viral DNA into host cells DNA

Answer 2

integrase

Question 3

How is lifelong infection maintained in HIV

Answer 3

by infection of monocytes and macrophages–HIV replicates and is protected within these cells from the immune system

Question 4

List the modes of HIV transmission

Answer 4

1. sexual activity
2. blood products
3. IV drug use with needle sharing
4. vertical transmission
5. needle stick

Question 5

How is the HIV virus NOT spread

Answer 5

mosquito bites
casual contact–kissing, sharing food
not transmitted in saliva, urine, tears or sweat

Question 6

What is the most common method of HIV transmission

Answer 6

sex

Question 7

Why are women more likely than men to get HIV with vaginal intercourse?

Answer 7

20X more likely

due to prolonged exposure to seminal fluids

Question 8

Highest sexual risk for HIV transmission

Answer 8

receptive anal > insertive anal > vaginal

Question 9

List some blood products through which HIV may be spread

Answer 9

whole blood
concentrated RBCs
platelets
WBC
concentrated clotting factors and plasma 
(not assoc. with gamma globulins)

Question 10

What screens are performed on donor blood products?

Answer 10

EIA for HIV1 and HIV2, and for p24 antigen

Question 11

3 ways of HIV vertical transmission

Answer 11

transplacental
during delivery
breast milk

Question 12

Risk of contraction (%) with needle stick

Answer 12

approx. 0.3%

Question 13

Why do HIV + patients experience immunosuppression?

Answer 13

• immunosuppression is the result of HIV induced CD4 T cell death
• CD4 cells are the mediators of the acquired immune response (humoral and cell mediated)–therefore, destruction of CD4 cells leads to immunosuppression

***infection of CD4 cells by HIV virions leads to the expression and integration of viral protein gp160 n CD4 cell cytoplasmic membrane

Question 14

What protein is expressed in HIV infected CD4 T cell cytoplasmic membranes?

Answer 14

gp160

Question 15

Describe the three mechanisms of HIV induced CD4 T cell death in HIV infection

Answer 15

1. binding of the gp160 to adjacent CD4 receptors on the same T helper cell membrane during budding results in tearing of the T cell membrane
2. binding of the gp160 to other CD4 cells, resulting in cell fusion and the formation of a multinucleated giant cell
3. expression of gp160 on CD4 cell cytoplasmic membrane marks it as nonself, resulting in autoimmune destruction by CD8 cytotoxic T-killer cells

(likely kills CD4s by directly inhibiting host cell protein synthesis as well)

Question 16

HIV train analogy: what is the speed of the train? what is the length of track left?

Answer 16

1. speed of train = viral load…the higher the viral load, the faster the patient will die without treatment
2. the length of track left = CD4 cell count… the higher the CD4 count, the more time the patient has before they succumb to opportunistic infections due to decreased immune system

Question 17

Describe the natural history of HIV

Answer 17

1. initial decline in CD4 cells and spike in viral load
2. Viral load then becomes low (due to overcompensation of CD4 cell production) and eventually will start to rise while CD4 cell count slowly descends
   * *the higher the viral load at which is stabilizes can be an indicator for how long before progresses to AIDS

Question 18

Name the methods used to diagnose HIV

Answer 18

ELISA and Western Blot confirmation

Question 19

How long after infection do antibodies begin to appear in circulation

Answer 19

2-12 weeks

Question 20

What is the standard blood screening test for HIV? How sensitive it is?

Answer 20

ELISA

99,5%

Question 21

What is the most commonly used confirmatory test for HIV after ELISA?

Answer 21

Western Blot

assay takes advantage of the fact that multiple HIV antigens of different, well characterized molecular weights elicit the production of specific antibodies

these antigens can be separated on the basis of molecular weight, and antibodies to each component can be detected as discrete bands on the Western blot

Question 22

What are the factors associated with false positive EIA tests?

Answer 22

antibodies to class II antigens
auto antibodies
hepatic disease
recent influenza vaccination
acute viral infections

this is why you do a confirmatory western blot

Question 23

What does it mean when an HIV+ person undergoing early treatment subsequently shows a negative EIA?

Answer 23

NOT clearing of infection–level of ongoing exposure just isnt high enough to maintain a detectable antibody response

Question 24

If a new patient has a positive or indeterminate EIA and a negative Western blot… do they have HIV?

Answer 24

No–definitely not. EIA was false positive.

Question 25

What is conclusive evidence of HIV infection?

Answer 25

A Western blot demonstrating antibodies to products of all three of the major genes of HIV (gag, pol and env) is conclusive evidence of infection with HIV

Question 26

Why are HIV+ patients more likely to contract diseases like Hep B/C and other STIs?

Answer 26

1. are immunocompromised, especially if not treated
2. they are typically more likely to be participating in sexual acts with other individuals that are more likely already in possession of an STI (although under no circumstances should this assumption be made for an HIV+ person–simply statistical correlation)

Question 27

HIV: bacterial opportunistic infections

Answer 27

staph aureus
staph epidermidis
haemophilus influenzae
strep pneumo
m. tuberculosis
m. avium complex

Question 28

HIV: fungal opportunistic infections

Answer 28

candida albicans
cryptococcus neoformans
histoplasma capsulatum
coccidioides immitis

Question 29

HIV: viral opportunistic infections

Answer 29

herpes zoster
epstein-barr virus
herpes simplex virus
cytomegalovirus

Question 30

HIV: protozoal opportunistic infections

Answer 30

pneumocystis carinii pneumonia
toxoplasma gondii
cryptosporidium
microsporidia

Question 31

What is the most common opportunistic infection in HIV+ patients

Answer 31

pneumocystis carinii pneumonia (PCP/PJP)

Question 32

Tx/prevent pneumocystis carinii pneumonia

Answer 32

TMP/SMP given prophylactically when CD4 drops below 200-250

Question 33

Tx/prevention for toxoplasmosis

Answer 33

treat with pyrimethamine/sulfdiazine

prophylaxis with TMP/SMX (same as PCP!!)

Question 34

Tx/prevention for M. TB

Answer 34

treatment same as with non-HIV patient

Question 35

Tx/prevention for MAC

Answer 35

azithromycin or clarithromycin DAILY

Question 36

Tx/prevention for HSV, VZV

Answer 36

acyclovir

Question 37

Tx/prevention for candida albicans

Answer 37

oral clotrimazole, nystatin or fluconazole

Question 38

When might HIV patients be able to come off prophylaxis?

Answer 38

once they have a CD4 count of 200 or above for more than 6 months after ART has been initiated

Question 39

HIV treatment guidelines

Answer 39

act earlier and more aggressively than old guidelines

start ART if ONE of following is tru:
1. CD4 count is