ART therapy for HIV patients (anti-retroviral therapy) Flashcards
average number of years to be lived at age 25 after starting ART is about
40-50 years
what indicates extent of HIV induced damage already suffered
CD4 count
major indicator of immune function and predictor of disease progression is…?
CD4 count
adequate response to ART is….
CD4 increase 50-150 cells/microliter per year
and
HIV RNA below detection (
CD4 monitoring procedure
check baseline twice
then atleast every 3-6 months
ART …usually monotherapy or combo?
mono is NOT standard of care
combo is used.
goals of ART
maximum suppression of viral replication
preserve or restore effective immune response against HIV
delay progressive immune dysfunction
prevent HIV transmission
improve quality of life and overall survival
regardless of viral load, there is a low risk of progression if CD4 count is …
greater or equal to 350
regardless of CD4 count, ART initiation is recommended for 6 conditions:
1 history of AIDs defining illness 2 pregnant women 3 HIV associated nephropathy 4 HepB coinfection, when HBV treatment is indicated 5 acute opportunistic infections 6 age >50 yo
when to start ART based on CD4 count?
exact is unknown BUT evidence supports starting ART at higher counts
currently –> ART for all
ART is strongly recommended for all ________ individuals
HIV infected
A1 recommendation for ART
means strong recommendation with high quality evidence (1+ randomized control trials)
3 reasons for deferral of ART?
- huge barriers to adherence
- if co-morbidities complicate or prohibit ART
- elite controllers and long-term non-progressors
early ART may prevent ____
HIV related end organ damage
ART in relation to HIV sexual transmission
has been shows to prevent transmission to a sexual partner
should be considered in patients who are at risk of transmitting HIV to sexual partner
combo therapy blocks HIV replication ______
at multiple different steps
if virus cant replicate, it cant mutate –> less resistance
HIV lifecycle
binding and fusion - HIV enters CD4 cells with binding to CD4R and co-receptor (either CCR5 or CXCR4) and releases RNA into cell
reverse transcription - HIV RNA is changed to DNA by HIV RT
integration - new HIV DNA enters CD4 nucleus and HIV integrase combines the HIV DNA and the CD4 DNA
transcription - virus integrated into CD4 cell and commands it to make new HIV proteins
assembly - HIV protease cuts proteins and those piece merge with HIV RNA = new viruses
budding - buds out of CD4 cell to infect other cells
what kind of inhibitor is maraviroc ?
entry inhibitor (CCR5 antagonist)
what kind of inhibitor is fuzeon
fusion inhibitor
what kind of inhibitor is AZT?
RT inhibitor
what kind of inhibitor is raltegravir?
integrase inhibitor
what kind of inhibitor is indinavir?
protease inhibitor
what does it mean that HIV is a retrovirus?
that means that its genetic info is stored on single stranded RNA instead of dsDNA and to replicate HIV uses reverse transcriptase to convert RNA to DNA
NRTIs and NNRTIs both exert effect over
reverse transcriptase
NRTIs and NNRTIs
NRTIs = Z-LASTED NNRTIs = N-DEER
zidovudine lamivudine abacavir stavudine tenofovir emtricitabine didanosine
nevirapine delavirdine efavirenz etravirine rilpivirine
integrase inhibitors
end in -gravir
raltegravir
elvitegravir
dolutegravir
what kind of inhibitor is enfuvirtide
a fusion inhibitor
ART combinations
2 NRTIs and 1 PI
2NRTIs and 1 II
1 NNRTI and 2 NRTIs
what 3 NRTIs also have activity against hepB
lamivudine
emtricitabine
tenofovir
what NRTI causes lactic acidosis
stavudine
which NRTI causes neuropathy and pancreatitis
zalcitabine
which NRTI is the safest?
lamivudine
what drug should NOT be used with HLAB5701
abacavir
since it causes anaphylaxis hyppersensitivity
what drug is the 1 nucleotide RT inhibitior?
tenofovir
—the others are nucleoside RT inhibitors
which ART drug can cause fanconi’s syndrome?
tenofovir
this syndrome is renal tubular dysfunction = phosphaturia and glucosuria
what combo is used in PrEP
pre exposure prophylaxis is made of emtricitibine + tenofovir
k103N mutation
confers resistance to efavirez and other NNRTIs
efavirenz
NNRTI that is backbone to ART (combine with tenofovir and emtricitabine)
crosses BBB - nightmares and teratogen
common triple ART combo
tenofovir + emtricitibine + efavirenz = ATRIPLA
etravirine
NNRTI that doesnt have same mutation resistance KN103 as efavirenz
and no vivid dreams
not as potent
cannot be used with 2 NRTIs
why are protease inhibitors so toxic?
because our cellular proteases are also blocked
and interacts with cytp450
all protease inhibitors can cause….
insulin resistance, hyperglycemia, and diabetes
dyslipidemia and fat redistribution
increased risk for MI
protease inhibitors
ritonavir indinavir atazanavir lopinavir darunavir
RTV boost
ritonavir (protease inhibitor) used at low doses with other protease inhibitors
indinavir
protease inhibitor that has effects on kidney (nephrolithiasis, sterile pyuria)
so drink lots of water on this drug
fusion inhibitors
T20 or enfuvirtide
subcutaneous injection
blocks HR1 region of Gp41 so that HIV cannot bind and enter the Cd4 cell
prevents HR1 and HR2 interaction
maraviroc
ccr5 chemokine receptor antagonist
inhibits HIV binding to ccr5 receptor and inhibits entry
some patients lack ccr5 so not always effective
co receptor tropism
HIV may use either ccr5 or cxcr4 to enter the host cell
can be dual or mixed
R5 virus
X4 virus
d/M virus
raltegravir
targets the HIV1 integrase so cannot integrate into host dna
WHICH combo is better?
atripla (tenofovir, emtricitabine + efavirenz) or dolutegravir/abacavir/3TC?
dolutegravir + 3TC/abacavir
better tolerated and suppresses HIV faster
FIRST LINE recommended as of 2015
elvitegravir
new HIV integrase stand transfer inhibitor
cobicistat
no activity against HIV but it does act as a pharmacokinetic enhancer of elvitegravir
OI prophylaxis can stop for the following at what CD4 level?
1) MAC
2) CMV
3) PCP
1 ) >100
2) >150
3) >200
HIV ART therapy is recommended for all ____
preganant women regardless of cd4 and viral loads
if viral load is >1000 at delivery …
do a C section
what agent should you NOT use with pregnanct women
efavirenz (teratogen)
any “d” drugs = lactic acidosis and hepatosteatosis
