HIV Flashcards
HIV structure
Diploid genome
2 RNA enclosed in concord capsid (P24)
Surrounded by lipid bilayer - envelope
HIV structural genes
gag gene - p24 capsid
env gene - gp120 and gp41
pol gene - reverse transcriptase and integrase
Reverse transcriptase
enzyme in capsid injected w/ RNA into host cell to synthesize dsDNA from HIV RNA
integrates into host genome via integrase
Attachment to internalization process for HIV
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
CCR5 receptor mutation
homozygous receptor mutation: no binding spot for R5 viruses = immune
hterozygous CCR5 mutation = slower course
Draw HIV infection graph of CD4, anti p24, anti gp120 Abs, virus and p24 Ag
page 365
AIDS criteria
CD4 less than 200
less than 14% lymphocytes are CD4
AIDS defining conditions: pneumocystis jirovecii pneumonia (PCP)
Neonate HIV testing
will have false + as mom’s Ab will cross plaenta
use viral load for dx - PCR
Pneumocystis jirovecii pneumonia
interstitial infiltrates on CXR
CD4 count less than 200
Mycobacterial infections in AIDS
M. tuberculosis
MAC aka MAI
CD4 count less than 50
Histoplasmosis in AIDS
causes systemic dz - HSM, fever, cough
CD4 count less than 150
Cryptococcus neoformans in AIDS
causes cryptococcal meningitis
Toxoplasmosis in AIDS
MULTIPLE ring enhancing lesions on brain MRI
CMV in AIDS
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”
Progressive multifocal leukencephalopathy (PML)
reactivation of latent JC virus
AIDS dementia
d/t HIV virus itself
Cyrptosporidiosis
Cryptosproidium sp - esp C. parvum
Chronic watery diarrhea
Candidiasis in AIDS
Oral thru - fluffy white lesions of the mouth and tongue
Esophageal candidiasis
CD4 less than 100
Oral hairy leukoplakia
EBV
shaggy lesion on sides of tongue that does not scrape off
Kaposi sarcoma
HHV8
vascular tumor of skin, mucous membranes, or internal organs
Bacillary angiomatosis in AIDS
Bartonella henseale
looks like cherry angiomas
numerous superficial vascular lesions
Non-hodgkin lymphomas in AIDS
Primary CNS lymphoma - SOLITARY ring-enhancing lesion
Large B cell lymphoma
assoc: EBV coinfection
Squamous cell carcinoma of cervix and/or anus in AIDS
assoc w/ HPV types 16, 18
Prophylaxis for CD4 less than 200
PCP prophylaxis: TMP-SMX
Sulfa allergy - Dapsone
pentamidine aerosol
Prophylaxis for CD4 less than 100
Add on Toxoplasmosis prophylaxis if + IgG
-TMP-SMX (already for PCP)
Sulfa allergy: dapsone + pentamidine + leucovorin
Prophylaxis for CD4 less than 50
MAC prophylaxis - azithromycin once/week
Protease Inhibitors
prevent development of new viruses
halt replicative processes
-navir Amprenavir Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Nelfinavir Ritonavir Saquinavir Tipranavir
Side effects of Protease inhibitors
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
Nucleoside reverse transcriptase inhibitors (NRTIs)
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
Zidovudine
AZT
newborns of HIV moms
HIV + at time of delivery if no antiviral tx
Side effects of NRTIs
Zidovudine: Bone marrow suppression - anemia, leukopenia, GI intolerances
Pancreatitis and peripheral neuropathy: Didanosine, zalcitabine, stavudine
Hepatosteatosis (elevated LFTs): didanosine, stavudine
HSR - life threatening - Abacavir
NNRTIs
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
Enfuvirtide
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
Integrase inhibitors
Dolutegravir
Elvitegravir
Raltegravir
well tolerated
inhibit entering host DNA
Maraviroc
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
