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Immuno mikro eng > Treatment of HIV and Opportunistic Infections > Flashcards

Treatment of HIV and Opportunistic Infections Flashcards

1
Q

Why can full eradication of HIV not be achieved through antiretrovirals?

A

A pool of latently infected CD4 cells is established during early stages of HIV infection

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2
Q

Why might it be difficult to achieve viral suppression in some cases?

A

Due to pre-existing mutations, even in patients which haven’t seen therapy before

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3
Q

What are the 6 different classes of HIV drugs? Which are never relied on unless last line?

A
  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

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4
Q

What do first line treatment regimens consist of?

A

Two NRTIs + a backbone

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5
Q

What is a backbone?

A 
An integrase inhibitor (first line)
or 
Boosted PI
or 
One NNRTI (no longer first line due to CNS effects)
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6
Q

What are the two most common 2-NRTI backbones?

A
  1. Abacavir / lamivudine

2. Tenofovir / emtricitabine

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7
Q

Why are integrase inhibitors really good?

A

Low pill burden
Well tolerated
Fewer drug interactions
Newest agent + high barrier to resistance

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8
Q

What was the first integrase inhibitor available and what are its side effects?

A

Raltegravir

Well-tolerated minus GI side effects
Potential CPK elevations / rhabdomyolysis (similar to daptomycin)

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9
Q

What are the two drug interactions we worry about with raltegravir?

A

Substrate of secondary metabolism enzymes (not a CYP inhibitor):
Dose must be doubled with rifampin
Binds divalent cations

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10
Q

What is Elvitegravir and what does it need to be given with?

A

An integrase inhibitor, needs to be given with cobicistat, a CYP3A4 inhibitor, for boosting

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11
Q

What side effects do we worry about with elvitegravir / cobicistat?

A

Cobicistat inhibits creatinine secretion like TMP
Tenofovir is given with elvitegravir and is nephrotoxic - patient needs a creatinine clearance of >30 (nitrofurantoin was >60)

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12
Q

What is one drug interaction of ALL integrase inhibitors?

A

Binds divalent cations - similar to FQ and tetracyclines

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13
Q

Which integrase inhibitor is super lit and why?

A

Dolutegravir - has a long-halflife so you can do once-daily dosing

Also has higher genetic barrier to resistance than other integrase inhibitors

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14
Q

In what way is dolutegravir similar to colbicistat?

A

Slightly blocks tubular secretion of creatinine

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15
Q

What drug-drug interactions do we worry about with dolutegravir?

A

Other than divalent cations:

It doubles metformin concentrations, and it is CYP-metabolized so dose needs to be doubled with Rifampin

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16
Q

What is the mechanism of action of protease inhibitors?

A

Bind HIV protease, which are needed to activate the HIV polyproteins

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17
Q

What is Ritonavir and its use?

A

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

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18
Q

What is the preferred PI based regimen?

A

Darunavir + ritonavir

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19
Q

What are the side effects of PI based regimens?

A

Dyslipidemia, fat maldistribution, insulin resistance, GI side effects including diarrhea, and skin rash

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20
Q

What are the advantages and disadvantages of PI based regimens?

A

Advantages: High genetic barrier to resistance
Disadvantages: Metabolic complications, GI side effects, and CYP3A4 issues

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21
Q

What is the preferred NNRTI? When is it not preferred?

A

Efavirenz

Not preferred during pregnancy because it will “Ef” your baby up with neural tube defects

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22
Q

What is the preferred alternative to Efavirenz during pregnancy?

A

Nevirapine - it’s “nevir” gonna fuq up your baby

23
Q

What is the mechanism of action of NNRTI’s and what about them is both good / bad?

A

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

24
Q

What are the scary adverse effects of Efavirenz other than NTDs?

A
  1. CNS / psychiatric symptoms leading to a 2-fold increase in suicide
  2. Rash / Steven-Johnsons Syndrome is possible
25
Q

What are the side effects of concern with Nevirapine?

A

Skin rash and hepatotoxicity

26
Q

What is the mechanism of action of NTRIs?

A

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

27
Q

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

A
  1. Lactic acidosis

2. Hepatic steatosis / lipoatrophy

28
Q

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

A

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

Associated with one particular HLA allele - test for this!

29
Q

What is the safest and most well tolerated NRTI?

A

Lamivudine

30
Q

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

A

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

31
Q

Why is zidovudine now rarely used?

A

It was the original NRTI (AZT)

No longer used due to bone marrow toxicity

32
Q

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

A

Enfuvirtide

Binds to gp41, needed for entry of virus into cell

33
Q

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

A

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

34
Q

What is Maraviroc? When is it useful?

A

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

35
Q

What is the metabolism of Maraviroc?

A

CYP3A4

36
Q

What are the three side effects of concern for Maraviroc?

A
  1. Rash / pruritis (From immune dysfunction)
  2. Hepatotoxicity
  3. Arthralgia / myalgia
37
Q

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

A

CD4 <200

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

38
Q

What is secondary prophylaxis as it relates to PCP pneumonia?

A

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

39
Q

What is the PCP treatment of choice?

A

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

40
Q

What is pentamidine and when is it used?

A

Can be used in PCP for prophylaxis or leishmania

Interferes with protozoal RNA / DNA/protein synthesis

41
Q

What are the adverse drug effects and interactions of pentamidine?

A

ADE: Bone marrow suppression, hepatoxicity, nephrotoxicity

Interactions: CYP2C19 substrate - interacts with AZOLE antifungals

42
Q

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

A

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

Stopped when CD4 > 100 for 3 months

43
Q

What is the MAC treatment?

A

Two or more anti-mycobacterial drugs to prevent resistance.

First line: Clarithromycin + Ethambutol + sometimes rifabutin

44
Q

What is rifabutin?

A

A derivative of rifampin, still induces CYP3A4 though

45
Q

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

A

When CD4 <100

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

46
Q

What is the prophylaxis and treatment for Cryptosporidiosis??

A

Prophylaxis - none, just get CD4 count back up

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

47
Q

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

A

CD4 < 100

Prophylaxis: TMP / SMX or dapsone

48
Q

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

A

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

Penetrates BBB well and you need to treat CNS infection

49
Q

What is the mechanism of action of pyrimethamine?

A

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

50
Q

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

A

Pyrimethamine causes bone marrow suppression.

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

51
Q

What is the metabolism of pyrimethamine? Pentamidine?

A

Pyrimethamine: CYP3A4
Pentamidine: CYP2C19

52
Q

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

A

CD4 < 100, same concern as Toxo and Crypto

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

53
Q

What is the primary treatment for CMV + side effect?

A

Ganciclovir / valganciclovir. Worry about bone marrow suppression

54
Q

How do you remember the two protease inhibitors given together?

A

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!

Immuno mikro eng (56 decks)

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