Treatment of HIV and Opportunistic Infections Flashcards Preview

Immunology / Micro > Treatment of HIV and Opportunistic Infections > Flashcards

Flashcards in Treatment of HIV and Opportunistic Infections Deck (54):

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?

1. Nukes - Nucleoside Reverse Transcriptase Inhibitors
2. Nonnukes - Non-nucleoside RT inhibitors
3. Protease Inhibitors
4. Integrase inhibitors
5. CCR5 antagonists
6. 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)
Boosted PI
One NNRTI (no longer first line due to CNS effects)


What are the two most common 2-NRTI backbones?

1. 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?


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?


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?

1. CNS / psychiatric symptoms leading to a 2-fold increase in suicide
2. Rash / Steven-Johnsons Syndrome is possible


What are the side effects of concern with Nevirapine?

Skin rash and hepatotoxicity


What is the mechanism of action of NTRIs?

Like acyclovir, they implant into the RT chain and act as chain terminators


What are the two class adverse events to remember for NRTI's?

1. Lactic acidosis
2. Hepatic steatosis / lipoatrophy


What is the reaction to test for in Abacavir (part of the standard Abacavir / lamivudine regimen)?

Abacavir hypersensitivity reactions, with fever, rash, fatigue, and abdominal pain

Associated with one particular HLA allele - test for this!


What is the safest and most well tolerated NRTI?



What are the side effects of concern with tenofovir and how has this been mitigated?

Renal toxicity / Fanconi syndrome - avoided in renal insufficiency

Now made as a prodrug which converts to active form in target cells, keeping serum concentrations lower


Why is zidovudine now rarely used?

It was the original NRTI (AZT)

No longer used due to bone marrow toxicity


What is currently the only drug in the fusion inhibitor class, and what is its mechanism of action?


Binds to gp41, needed for entry of virus into cell


What is the the major side effect of concern for enfuvirtide?

Injection site reactions, since it must be given twice daily subcutaneously


What is Maraviroc? When is it useful?

A CCR5 antagonist -> given to treatment experienced patients whose HIV is still M-tropic


What is the metabolism of Maraviroc?



What are the three side effects of concern for Maraviroc?

1. Rash / pruritis (From immune dysfunction)
2. Hepatotoxicity
3. Arthralgia / myalgia


At which CD4 count do we worry about PCP and what is the prophylaxis?

CD4 <200

Prophylaxis: TMP / SMX, or dapsone (similar to sulfa, PABA antagonist), also pentamidine


What is secondary prophylaxis as it relates to PCP pneumonia?

If patient has had PCP, they will get TMP/SMX prophylaxis for life


What is the PCP treatment of choice?

High dose TMP/SMX for 21 days, with option of corticosteroids to reduce inflammation in moderate/severe


What is pentamidine and when is it used?

Can be used in PCP for prophylaxis or leishmania

Interferes with protozoal RNA / DNA/protein synthesis


What are the adverse drug effects and interactions of pentamidine?

ADE: Bone marrow suppression, hepatoxicity, nephrotoxicity

Interactions: CYP2C19 substrate - interacts with AZOLE antifungals


When should Mycobacterium avium complex prophylaxis start? What is it? When should it be stopped?

When CD4 < 50, it is Azithromycin or Clarithromycin once weekly

Stopped when CD4 > 100 for 3 months


What is the MAC treatment?

Two or more anti-mycobacterial drugs to prevent resistance.

First line: Clarithromycin + Ethambutol + sometimes rifabutin


What is rifabutin?

A derivative of rifampin, still induces CYP3A4 though


What patients are at greatest risk of Cryptosporidiosis? What is the presentation?

When CD4 <100

Present with acute onset of non-bloody watery diarrhea and abdominal symptoms


What is the prophylaxis and treatment for Cryptosporidiosis??

Prophylaxis - none, just get CD4 count back up

Treatment: symptomatically rehydrate. Possible Nitazoxanide (Knit-Sox)


When is T. gondii prophylaxis recommended, and what is the most common presentation? What is the prophylaxis?

CD4 < 100

Prophylaxis: TMP / SMX or dapsone


What is the treatment for T. gondii encephalitis and why?

Pyrimethamine (pyramid hat) + sulfadiazine (sulfur eggs next to cat)

Penetrates BBB well and you need to treat CNS infection


What is the mechanism of action of pyrimethamine?

Inhibits parasitic dihydrofolate reductase (similar to TMP, synergistic with sulfadiazine, a sulfa derivative)


What is co-administered with pyrimethamine / sulfadiazine and why?

Pyrimethamine causes bone marrow suppression.

Leucovorin is a reduced form of folic acid, allows purine synthesis in our cells but not the parasite


What is the metabolism of pyrimethamine? Pentamidine?

Pyrimethamine: CYP3A4
Pentamidine: CYP2C19


At what CD4 count are we worried about CMV and what is its most common presentation?

CD4 < 100, same concern as Toxo and Crypto

Concern for retinitis, but can also caused colitis, pneumonitis, and neurological disease


What is the primary treatment for CMV + side effect?

Ganciclovir / valganciclovir. Worry about bone marrow suppression


How do you remember the two protease inhibitors given together?

In the sketchy sketch: ritonavir = right on! kids high-fiving

Darunavir - looks like old times, kid pulling the sword from the stone. Runescape! Da Runa -vir!

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