HIV

Question 1

HIV structure

Answer 1

Diploid genome
2 RNA enclosed in concord capsid (P24)

Surrounded by lipid bilayer - envelope

Question 2

HIV structural genes

Answer 2

gag gene - p24 capsid
env gene - gp120 and gp41
pol gene - reverse transcriptase and integrase

Question 3

Reverse transcriptase

Answer 3

enzyme in capsid injected w/ RNA into host cell to synthesize dsDNA from HIV RNA

integrates into host genome via integrase

Question 4

Attachment to internalization process for HIV

Answer 4

gp120 grabes CD4 surface receptor on T cells and M0
–> conformational change exposing binding sites for coreceptor
- CCR5 = R5 virus
-CXCR4 = X4 virus
Both = dual tropism

gp41 - fuse and entry into cell

Question 5

CCR5 receptor mutation

Answer 5

homozygous receptor mutation: no binding spot for R5 viruses = immune

hterozygous CCR5 mutation = slower course

Question 6

Draw HIV infection graph of CD4, anti p24, anti gp120 Abs, virus and p24 Ag

Answer 6

page 365

Question 7

AIDS criteria

Answer 7

CD4 less than 200
less than 14% lymphocytes are CD4
AIDS defining conditions: pneumocystis jirovecii pneumonia (PCP)

Question 8

Neonate HIV testing

Answer 8

will have false + as mom’s Ab will cross plaenta

use viral load for dx - PCR

Question 9

Pneumocystis jirovecii pneumonia

Answer 9

interstitial infiltrates on CXR

CD4 count less than 200

Question 10

Mycobacterial infections in AIDS

Answer 10

M. tuberculosis
MAC aka MAI

CD4 count less than 50

Question 11

Histoplasmosis in AIDS

Answer 11

causes systemic dz - HSM, fever, cough

CD4 count less than 150

Question 12

Cryptococcus neoformans in AIDS

Answer 12

causes cryptococcal meningitis

Question 13

Toxoplasmosis in AIDS

Answer 13

MULTIPLE ring enhancing lesions on brain MRI

Question 14

CMV in AIDS

Answer 14

CMV retinitis
CD4 less than 50

retinal necrosis and hemorrhage: “cheese pizza” or “ketchup and mustard” appearance

Infected cells are enlarged, with dark intranuclear inclusion bodies “owl’s eyes”

Question 15

Progressive multifocal leukencephalopathy (PML)

Answer 15

reactivation of latent JC virus

Question 16

AIDS dementia

Answer 16

d/t HIV virus itself

Question 17

Cyrptosporidiosis

Answer 17

Cryptosproidium sp - esp C. parvum

Chronic watery diarrhea

Question 18

Candidiasis in AIDS

Answer 18

Oral thru - fluffy white lesions of the mouth and tongue

Esophageal candidiasis

CD4 less than 100

Question 19

Oral hairy leukoplakia

Answer 19

EBV

shaggy lesion on sides of tongue that does not scrape off

Question 20

Kaposi sarcoma

Answer 20

HHV8

vascular tumor of skin, mucous membranes, or internal organs

Question 21

Bacillary angiomatosis in AIDS

Answer 21

Bartonella henseale
looks like cherry angiomas
numerous superficial vascular lesions

Question 22

Non-hodgkin lymphomas in AIDS

Answer 22

Primary CNS lymphoma - SOLITARY ring-enhancing lesion

Large B cell lymphoma

assoc: EBV coinfection

Question 23

Squamous cell carcinoma of cervix and/or anus in AIDS

Answer 23

assoc w/ HPV types 16, 18

Question 24

Prophylaxis for CD4 less than 200

Answer 24

PCP prophylaxis: TMP-SMX

Sulfa allergy - Dapsone
pentamidine aerosol

Question 25

Prophylaxis for CD4 less than 100

Answer 25

Add on Toxoplasmosis prophylaxis if + IgG
-TMP-SMX (already for PCP)

Sulfa allergy: dapsone + pentamidine + leucovorin

Question 26

Prophylaxis for CD4 less than 50

Answer 26

MAC prophylaxis - azithromycin once/week

Question 27

Protease Inhibitors

Answer 27

prevent development of new viruses
halt replicative processes

-navir
Amprenavir
Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir

Question 28

Side effects of Protease inhibitors

Answer 28

MC: GI intolerance
Inhibit cytochrome P450 (esp Ritonavir) - exploit to increase concentration of other HIV meds

hyperlipidemia/hyperglycemia

Lipodystrophy - fat accumulation in abdomen, lost in face, extremities –> buffalo hump

Ritonavir: pancreatitis
Nephrolithiasis - indinavir, atazanavir
Atazanavir : increased bilirubin

Question 29

Nucleoside reverse transcriptase inhibitors (NRTIs)

Answer 29

inhibit HIV reverse transcriptase
Nuceloside analogs - Gs or Cs

competitive inhibitors of functional site
have to be phosphorylated/activated by thymidine kinase

Give for occupational exposure for 4 weeks - part of 3 drug regimen

abacavir
didanosine
emtricitabine
lamivudine
Tenofovir (nucleotide analog)
Zidovudine

Question 30

Zidovudine

Answer 30

AZT
newborns of HIV moms
HIV + at time of delivery if no antiviral tx

Question 31

Side effects of NRTIs

Answer 31

Zidovudine: Bone marrow suppression - anemia, leukopenia, GI intolerances

Pancreatitis and peripheral neuropathy: Didanosine, zalcitabine, stavudine

Hepatosteatosis (elevated LFTs): didanosine, stavudine

HSR - life threatening - Abacavir

Question 32

NNRTIs

Answer 32

noncompetitive inhibitor of reverse transcriptase - nonfunctional site
do no require phosphorylation to be active

Efavirenz
etravirine
Oelavirdine
nevirapine
rilpivirine

SE:
Rash
Efavirenz: Neuropsychiatric sx: nightmares, vivid dreams, dizziness, worsening depression
-false positive drug test for cannabinoids
-teratogenic

Rilpivirine - can’t take with meds that decrease gastric acid, must be taken w/ food

Question 33

Enfuvirtide

Answer 33

fusion inhibitor
en-envelope
fu-fusion

Binds gp41 –> inhibits fusion of HIV w/ host cell
-blocks infection of new cells

Injection only
Drug resistance

SE:
injection site reactions - tender nodules
increased risk bacterial pneumonia

Question 34

Integrase inhibitors

Answer 34

Dolutegravir
Elvitegravir
Raltegravir

well tolerated
inhibit entering host DNA

Question 35

Maraviroc

Answer 35

R5 virus specific

binds CCR5 - antagonist
inhibits gp120 conformational change –> cannot bind host cell effectively

Must check tropism - all must be R5 virus, no CXCR4 can be present