HIV - ARVs Flashcards
T or F: Antiretroviral therapy is essentially a fn’al cure for HIV
T
T or F: ARVs can be used in any combination to tx HIV
F
Six classes of HIV meds:
NRTIs (nucleoside reverse transcriptase inhibitors)
NNRTIs (non-nucleoside…)
Protease inhibitors
Integrase strand transfer inhibitors (INSTIs)
Fusion inhibitors
Chemokine receptor antagonist/entry inhibitors
What’re the standard NRTI combinations used in practice?
- TDF/FTC (tenofovir/emtricitabine)
- TAF/FTC (tenofovir/emtricitabine)
- ABC/3TC (abacavir/lamivudine)
MOA of NRTIs
phosphorylated to triphosphate form > competitively binds to HIV reverse transcriptase > terminates DNA chain elongation
Which NRTIs are also active against HBV?
3TC, FTC, and TDF/TAF (tenofovir)
What’s unique about TDF?
It’s a nucleotide, not a nucleoside (i.e. it’s already phosphorylated)
Notable AEs of TDF?
- Fanconi syndrome (proximal tubule reabsorption problems)
- renal failure
- decreased BMD
- HBV flareup if d/c’ed
T or F: TDF is hepatotoxic.
F
it’s nephrotoxic
What should be monitored in pts taking TDF?
SCr, urine protein, BMD
Why are TDF and TAF better than classic tenofovir?
because TDF and TAF are able to move from the gut into the blood and lymphoid cells, whereas classic tenofovir could not
What are some advantages of TAF over TDF?
Higher F and intracellular t1/2 > lower req’d dose and less plasma exposure to tenofovir
less renal tox (no Fanconi syndrome)
less eGFR effects
less BMD reductions
Why isn’t abacavir (ABC) used often
Convenience issues > ABC requires HLA-B testing to see if there’s a specific allele present (*5701) that increases risk of hypersensitivity rxn to it
ABC - If there is hypersensitivity to it, when would it show up?
At week 6 of ABC use
T or F: We should rechallenge ABC if hypersensitivity rxn occurs.
F > can result it death
Which two NRTIs are distinguished by a single fluorine atom?
3TC and FTC (the “F” is for fluorine)
NNRTIs: MOA?
binds to hydrophobic pocket of reverse transcriptase > active site changes shape > disrupts DNA chain elongation (prevents natural nucleosides from being incorporated into viral DNA)
NRTIs vs NNRTIs: which one is active against HIV-1? HIV-2? Both?
NRTIs: active against BOTH HIV-1/2
NNRTIs: active against HIV-1 only
What’s the issue w/ first gen NNRTIs?
low genetic barrier to resistance (single mutation in viral genome confers resistance)
Half life profile of NNRTIs?
They’re long (>24h)
Name 3 NNRTIs:
RPV (rilpivirine), efavirenz (EFV), doravirine (DOR)
How should rilpivirine be taken?
With foods that contain fat
What reduces rilpivirine absorption?
Protein shakes, higher pH
CI of rilpivirine?
PPIs, H2RAs, antacids (anything that reduces stomach acidity)
Important caution wrt RPV?
It prolongs QT interval > watch out when taking other drugs that do the same
Who should NOT receive RPV?
naive pts w/ viral loads >100,000 copies/mL > increased risk of tx failure
Major AEs of RPV?
severe rash, depression/mood changes, liver damange
How should efavirenz (EFV) be taken?
on an empty stomach
How is efavirenz affected by food?
its absorption is increased by high fat meals (hence why it should be taken on an empty stomach)
What kind of pts are given doravirine (DOR)?
Naive pts only
Name all NRTIs?
3TC, FTC, TAF, TDF, ABC
Protease inhibitor (PI) MOA?
inhibits the action of HIV-1/2 protease, an enzyme that cleaves two precursor proteins into smaller fragments.
Resistance profile of PI’s?
Resistance is RARE (high genetic barrier to resistance)
What kinds of pts should use protease inhibitors?
pts who fail other regimens due to resistance, and pts who have poor adherence
What do PI’s require to be taken concomitantly?
Pharmacokinetic booster
Name two PK boosters that may be used w/ PIs
ritonavir (RTV, /r), cobicistat (/c) (note: ritonavir is also a PI)
T or F: PIs can cause DM
T
RTV (/r, ritonavir) - How is absorption affected by food?
Its absorption is INCREASED by food
T or F: Cobicistat is used as a PI booster.
T
Cobicistat MOA:
CYP3A4 inhibitor (NOT a PI like ritonavir)
T or F: Cobicistat, like ritonavir, is a PI
F (it’s a 3A4 inhibitor)
What may be observed while taking cobicistat?
Increased serum creatinine by 10-15 µmol/L
If an increase of creatinine is observed while taking cobicistat (/c), when should it be this med be stopped?
if SCr rises higher than 10-15 µmol/L
Which PI has the highest genetic barrier to resistance?
Darunavir (DRV)
Which PI is the most preferred?
Daruavir (DRV)
How should DRV be taken?
With food (reduces GI irritation + increases absorption)
How should atazanavir (ATV) be taken?
With food (NOT on an empty stomach)
What does atazanavir require for it to be absorbed?
acidic envir
What is an important AE of ATV (a PI)?
Hyperbilirubinemia (jaundice and scleral icterus)
Name the PIs:
darunavir (DRV), atazanavir (ATV), cobicistat (/c) (technically NOT a PI), and ritonavir (RTV, /r)
MOA of integrase strand transfer inhibitors (INSTIs)?
Inhibits translated retroviral DNA strand from being inserted into host cell genes
Which HIV types are targeted by INSTIs?
HIV-1 and 2
T or F: Currently, ALL first-line regimens are INSTI based.
T
T or F: INSTIs have few DIs and are better tolerated relative to other ARVs.
T
T or F: Despite their better AE profile, INSTIs reduce viral load v. slowly.
F
quickly
List the INSTIs:
raltegravir (RAL)
elvitegravir (EVG)
dolutegravir (DTG)
bictegravir (BIC)
How should RAL be taken?
w/o respect to meals (absorption is higher w/ high fat meal, however)
Important DI w/ RAL
Avoid Al and Mg salts > chelation > reduced absorption
How should elvitegravir be taken?
with food (increases absorption) and with cobicistat
EVG should be separated from _____ by at least 2h
antacids
Which INSTI has a lower barrier to resistance?
EVG (elvitegravir)
How should dolutegravir (DTG) be taken?
without respect to meals (food increases extent and slows rate of absorption, but not sig)
Important DI of DTG
Avoid cations (Al, Ca, Mg, Fe, Zn salts) > take DTG 2h before or 6h after
Important AE of DTG?
Increased ALT and AST > may result in acute hepatitis
Which population should avoid DTG?
Pregnant women (possible neural tube defects)
Which INSTI do we often put pts on?
bictegravir (BIC)
How should bictegravir be taken?
w/o regard to meals
Important DI involving bictegravir
Interaction w/ cations (Ca, Mg, Al, Fe, sucralfate)
Why is bictegravir usually the new standard tx?
Due to it being a small, single tablet
