HIV Flashcards
tat
transactivator of transcription: enhances rate of transcription
drives from latent to active replicative state
rev
affects mRNA transport out of nucleus
nef
contribute to virus pahtogenesis; nonessential in cell culture
vpr
contribute to virus pahtogenesis; nonessential in cell culture
vpu
contribute to virus pahtogenesis; nonessential in cell culture
vif
contribute to virus pahtogenesis; nonessential in cell culture
env
gp160: gets cleaved to p120 and p41
envelope proteins
reverse transcriptase
generation of a sDNA copy of the genome after virus uncaring
req. for replication
p11
protease
req. for maturation
cleaved from pr170
p32
integrase
req. for replicaiton
cleaved to pr170
unique feature of HIV integration
does not req. cell division
gp120
receptor binding
gp41
membrane fusion activity
pol
polymerase/RT
cleaved from pr170
protein inhibitors
prevent cleavage of core protein
results in release of non infectious particles
What is gag cleaved into?
aka pr55 cleaved into 1. nucleocapsid (p7)-> binds RNA genome 2. capsid (p24)-> forms cylindrical core 3. matrix (p17)-> lines inner surface of viral envelope
RRE
rev response element
ELISA
detects p24 capsid protein and HIV Ab
Rapid oral, whole or serum test
HIV Ab detection
latent and active
Western blot
p24 and gp120 detection needed
most important HIV receptor in outcome of HIV infection
CCR5: delta 32 mutations
homozygous mutation in CCR5: infected, but never get full blown AIDS
heterozygotes: AIDS is developed more slowly
Nef deletion: also has long term survivors
RT-PCR
quantitates viral RNA levels
PCR
quantitates amount of provirus in lymphocytes (latent and actively dividing)
bDNA assay
no amplification needed
hybridization with highly ranched, labeled DNA probe
quantitate viral RNA levels in blood
preganancy HIV Tx
NRTI: lamivudine, zidovudine
NNRTI: Nevirapine
PI: Lopinavir/ritonavir
NRTIs
oral
NO CYP3A4
tenofovire, didanosine, abacavir, , emtricitabine
lamivudine, zidovudine, stavudine
NNRTIs
oral
efavirenz, nevirapine, delavirdine
HIV-1 protease inhibitors
atazanavir, ritonavir, darunavir, fosamprenavir, indinavir, lopinavir, saquinavir
fusion inhibitors
enfuvirtide
maravaroc
DNA strand transfer inhibitor
raltegravir
What is unusual about abacavir?
metabolized by alcohol dehydrogenase
nevirapine
induces CYP3A4 and 2B6: oral contraceptive failure
efavirenz
induces CYP3A4 and 2B6: oral contraceptive failure
OK with rifampin and rifabutin (CYP inducers) if dose is increased (because metabolized faster with CYP induction)
delavirdine
inhibits CYP3A4, CYP2D6, CYP2C9, CYP2C10
atazanavir
inhibits 3A4 and UGTNOT used with rifampin
daunavir and lopinavir
3A4 substrates
used with ritonavir to boost serum drug levels
ritonavir
inhibits 3A4, 2D6, P-gp, UGTNOT used with rifampin
enfuvirtide
NOT orally active
SC
cobicistat
oral
CYP3A4 inhibitor
use with: lopinavir
saquinavir
inhibits 3A4, UGT
NOT used with rifampin
atripla
once daily pill: complete regimen
MOST common
tenofovir, emtricitabine, efavirenz
NRTI side effects
BBW: lactic acidosis, hepatic disease (contra in abacavir)
AVOID ALCOHOLs :(
most often in obese women
NRTIs: pancreatitis
didanosine and stavudine
pain in back and digestion issues
NRTIs: neutropenia and anemia and myopathy
zidovudine
NRTIs: neuropathy
stavudine» didanosine
NRTIs: hypersensitivity
abacavir
NNRTIs: hypersensitivity
females
hypersensitivity
NNRTIs: vivid dreams and CNS symptoms
efavirenz
NNRTIs: contraindicated in pregnancy
efavirenz and delavirdine
NNRTI: SE
rash and hepatotoxicity
protease inhibitor SE
GI intolerance, lipodystrophy, hyperglycemia/DM, dyslipidemia, severe rash in steven johnson’s syndrome
*atazanavir most likey to get lipodystrophy
pneumocystis jiroveci or toxoplasmosis
trimethoprim-sulfamethoxazole
TB
isoniazid and pyridoxine
CMV retinitis
ganciclovir
valganciclovir (only oral one and prophylaxis too)
Res: mutation to viral kinase
NO viral kinase needed:
foscarnet
cidofovir
cryptococcus, candidiasis, endemic, fungal infections
fluconazole
valganciclovir: SE
leukopenia, neutropenia, thrombocytopenia, renal toxicity
CI: excretion is in excess of renal blood flow due to filtration and active renal tubular secretion; renal failure: accumulation over time
foscarnet: SE
hospital admin.
nephrotoxicity
need saline hydration by infusion pump because highly insoluble: can get genital ulcerations due to high levels of ionized drug in urine
EBV
vidarabine: applied to eye
nucleoside analog
Kaposi
cidofovir, IV
renal clearance, active tubular secretion; nephrotoxicity
