Treatment of HIV and Opportunistic Infections Flashcards
(54 cards)
Why can full eradication of HIV not be achieved through antiretrovirals?
A pool of latently infected CD4 cells is established during early stages of HIV infection
Why might it be difficult to achieve viral suppression in some cases?
Due to pre-existing mutations, even in patients which haven’t seen therapy before
What are the 6 different classes of HIV drugs? Which are never relied on unless last line?
- Nukes - Nucleoside Reverse Transcriptase Inhibitors
- Nonnukes - Non-nucleoside RT inhibitors
- Protease Inhibitors
- Integrase inhibitors
- CCR5 antagonists
- Fusion inhibitors
5/6 never relied upon unless resistance
What do first line treatment regimens consist of?
Two NRTIs + a backbone
What is a backbone?
An integrase inhibitor (first line) or Boosted PI or One NNRTI (no longer first line due to CNS effects)
What are the two most common 2-NRTI backbones?
- Abacavir / lamivudine
2. Tenofovir / emtricitabine
Why are integrase inhibitors really good?
Low pill burden
Well tolerated
Fewer drug interactions
Newest agent + high barrier to resistance
What was the first integrase inhibitor available and what are its side effects?
Raltegravir
Well-tolerated minus GI side effects
Potential CPK elevations / rhabdomyolysis (similar to daptomycin)
What are the two drug interactions we worry about with raltegravir?
Substrate of secondary metabolism enzymes (not a CYP inhibitor):
Dose must be doubled with rifampin
Binds divalent cations
What is Elvitegravir and what does it need to be given with?
An integrase inhibitor, needs to be given with cobicistat, a CYP3A4 inhibitor, for boosting
What side effects do we worry about with elvitegravir / cobicistat?
Cobicistat inhibits creatinine secretion like TMP
Tenofovir is given with elvitegravir and is nephrotoxic - patient needs a creatinine clearance of >30 (nitrofurantoin was >60)
What is one drug interaction of ALL integrase inhibitors?
Binds divalent cations - similar to FQ and tetracyclines
Which integrase inhibitor is super lit and why?
Dolutegravir - has a long-halflife so you can do once-daily dosing
Also has higher genetic barrier to resistance than other integrase inhibitors
In what way is dolutegravir similar to colbicistat?
Slightly blocks tubular secretion of creatinine
What drug-drug interactions do we worry about with dolutegravir?
Other than divalent cations:
It doubles metformin concentrations, and it is CYP-metabolized so dose needs to be doubled with Rifampin
What is the mechanism of action of protease inhibitors?
Bind HIV protease, which are needed to activate the HIV polyproteins
What is Ritonavir and its use?
It is a PI, but mainly used in HIV regimens as a POTENT CYP3A4 inhibitor, as a booster. All PIs interact with CYP3A4 to some degree
Being used less with colbicistat on the market now
What is the preferred PI based regimen?
Darunavir + ritonavir
What are the side effects of PI based regimens?
Dyslipidemia, fat maldistribution, insulin resistance, GI side effects including diarrhea, and skin rash
What are the advantages and disadvantages of PI based regimens?
Advantages: High genetic barrier to resistance
Disadvantages: Metabolic complications, GI side effects, and CYP3A4 issues
What is the preferred NNRTI? When is it not preferred?
Efavirenz
Not preferred during pregnancy because it will “Ef” your baby up with neural tube defects
What is the preferred alternative to Efavirenz during pregnancy?
Nevirapine - it’s “nevir” gonna fuq up your baby
What is the mechanism of action of NNRTI’s and what about them is both good / bad?
Suicide inhibitor of RT.
Their long halflife is good and bad: fewer pills are needed, but if compliance is not at least 95% there will be subtherapeutic concentrations and resultant low barrier to resistance
What are the scary adverse effects of Efavirenz other than NTDs?
- CNS / psychiatric symptoms leading to a 2-fold increase in suicide
- Rash / Steven-Johnsons Syndrome is possible
