HIV tx Flashcards
initial HIV tx regimen in naive pts
2NRTIs + INSTI
why multiple drugs for tx?
resistance develops quickly with a single agent so use 2-3
NRTI meaning
nucleoside/nucleotide reverse transcriptase inhibitors
NNRTI
non-nucleoside reverse transcriptase inhibitors
PIs
protease inhibitors
INSTIs
integrase strand transfer inhibitors
NRTIs MOA
inhibits conversion of HIV RNA to DNA by blocking the function of reverse transcriptase at active site and terminates DNA chain
TDF
tenofovir disoproxil fumarate
TAF
tenofovir alafenamide
NRTI associated inhibition of mitochondrial DNA function effects
lactic acidosis
hepatic steatosis
peripheral neuropathy
lipodystrophy
lamivudine and emtricitabine use
interchangeable but never used together
backbone of nearly all current antiretroviral tx regimens
which rx are also active against HBV?
lamivudine and emtricitabine (NRTIs)
lamivudine and emtricitabine side effects
most well tolerated NRTIs
rare headache, nausea, fatigue
abacavir indication
first line in combo with lamivudine and dolutegravir
triumeq
combo drug of abacavir, lamivudine and dolutegravir
abacavir side effects
hypersensitivity syndrome
- fever, abdominal pain, rash
- associated with HLA-B*5701 allele (need genetic testing)
cardio risk
TDF side effects
tenofovir disoproxil fumarate
decreased bone mineral density
decreased CrCl
Fanconi syndrome
TAF side effects
less than TDF, safer
greater antiviral activity lower dosing needed
adjust for CrCl
what is tenofovir
nucleotide adenosine 5imonophosphate derivative
truvada
TDF + emtricitabine (2 NRTIs)
Descovy
TAF + emtricitabine (2 NRTIs)
higher risk NRTIs used for resistant forms
didanosine
stavudine
zidovudine
NNRTIs MOA
inhibits conversion of HIV RNA to DNA by blocking the function of reverse transcriptase (binds at different site than NRTIs)
NNRTI downsides and effects
low barrier of resistance drug interactions hypersensitivity rxns neuro/psych effects hepatic clearance
efavirenz
NNRTI that is not very common in US
efavirenz side effects
neuro: vivid dream, insomnia, hallucinations
teratogenic
hepatotoxic
rash
drug interactions because it is a CYP3A4 inducer/inhibitor
first generation NNRTIs (some tx failure)
nevirapine
efavirenz
delaviridine
2nd gen NNRTIs (better)
etravirine
doravirine
rilpivirine
should you take efavirenz with food?
NO on an empty stomach because high fat meal increases bioavailability
rilpivirine indication
NNRTI alternative first-line option in select treatment naive patients or as switch therapy for suppressed pts
*also can be used in combo with INSTI
rilvipirine side effects
drug interactions (CYP3A4) no PPIs because it needs an acidic environment for absorption
NNRTI based regimen
2 NRTIs +NNRTI
odefsey
TAF + emtricitabine + rilpivirine
Juluca
rilpivirine + dolutegravir (integrase inhibitor)
cabenuva
injection
rilpivirn + cabotegravir
protease inhibitors MOA
inhibition of HIV protease enzyme preventing formation and release of mature virions
PIs indication
high barrier to resistance, very potent
require admin with a booster agent
alternative first-line in combo with 2 NRTIs
HIV life cycle basic steps
binding fusion on CD4 cell reverse transcription integration replication assembly budding
Protease Inhibitors’ warnings
lipodystrophy nausea/vomiting diarrhea cholesterolemia insulin resistance cardiovascular risk drug interactions
PI booster agents
ritonavir or cobicistat
PI that is safe for pregnancy
Lopinavir/ritonavir
third gen PIs
atazanavir
darunavir
why use booster agents for PIs
less CYP3A4 inhibition
lower dosing frequency required so there are better blood concentrations
can you take atazanavir alone?
NO needs to be boosted with ritonavir or cobicistat + 2NRTIs
atazanavir side effects
N/V/D
Hyperbilirubinemia +/- jaundice
nephrolithiasis and cholelithiasis
symtuza
combo therapy
-darunavir-cobcistat-TAF-emtricitabine (1 tab PO daily)
Prezcobix
PI + booster
darunavir-cobicistat 1 tab PO
*as part of combination with 2 NRTIs
INSTIs MOA
prevents the insertion of DNA transcribed from the virus into human cell DNA by inhibiting integrase enzyme
INSTI indication
part of first-line regimen for treatment naive-patients
INSTI + 2 NRTIs
INSTI classwide effects
- drug interactions bc of CYP450 enzymes
- interacts with antacids
raltegravir adverse effects
rare myalgia, rash, liver toxicity
dolutegravir adverse effects
neurocognitive effects
weight gain
elevated serum creatinine
neural tube defects
less used INSTI
raltegravir because it is inferior to dolutegravir and has a lower barrier to resistance
2nd gen INSTIs
dolutegravir
bictegravir
Dolutegravir indication
preferred INSTI
more potent and less frequent dosing than raltegravir
Bictegravir (Biktaryvy) indication
first line recommendation, high barrier to resistance
single small tablet regimen
well-tolerated
cabotegravir
long acting injectable in combination with rilpivirine
*monthly injection
Dovato
dolutegravir + lamivudine (NRTI)
biktarvy
bictegravir + emtricitabine + TAF
genvoya
TAF-emtricitabine+elvitagravir+cobicistat
gp120 and gp41
HIV-1 surface glycoproteins gp120 and gp41 mediate viral binding to host target cells
gp120 binds to CD4 cell and causes conformational change
gp41 forms metastable conformation which allows for HIV penetration
entry inhibitors’ MOA
either inhibition of gp41 and gp120 to stop binding and fusion with target cell
maraviroc
entry inhibitor
CCR5 blocker that inhibits gp120 blocks HIV attachment to target cells
entry inhibitor types
fostemsavir
enfuvirtitide
maraviroc
ibalizumab
how to monitor ART patients
measure HIV RNA
-goal at 16-24 months is undetectable
measure CD4 count
-want an increase by 50-150 within first year
Pre-Exposure Prophylaxis
prophylactic therapy given to HIV negative patients who are at high risk of developing HIV
prophylaxis regimen for prep
Entricitabine/TDF (Truvada)
Emtricitabide/TAF (DEscovy-safer)
take daily!
Post-Exposure Prophylaxis (PEP)
taken within 72 hours of HIV exposure, anti-HIV rx to prevent development of HIV
occupational PEP
TDF/emtricitabine (Truvada) + raltegravir (INSTI)
non-occupational PEP
Truvada + Isentress
TDF+emtricitabine+(raltegravir or dolutegravir)
