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Parasitology/Virology > HIV Therapy > Flashcards

HIV Therapy Flashcards

1
Q

Who gets antiretroviral therapy?

A

Everyone!

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2
Q

When should you consider deferral of ART?

A

Significant barriers to adherence
Comodbidities complicate or prohibit ART
“Elite controllers” and long-term non-progressors (very few)

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3
Q

What are classes of antiretroviral agents?

A
  • Coreceptor binding inhibitors
  • Fusion inhibitors
  • Reverse transcription inhibitors (nucloside/nuclotide and non-nuclotide)
  • Integrase inhibitors
  • Protease inhibitors
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4
Q

What agent(s) are in class of Co-receptor Binding inhibitors?

A

Maraviroc

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5
Q

What is the mechanism of action of Maraviroc?

A

Binds CCR5 coreceptor, blocking HIV binding to host cell for entry

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6
Q

Is Maraviroc effective against all HIV-1?

A

Only works against CCR5, inactive against X4 or dual tropic virus

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7
Q

What should be done before giving Miraviroc?

A

“Trofile” to determine if virus is CCR5, CXCR4, or D/M

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8
Q

What agent(s) are in class of Fusion inhibitors?

A

Enfuvirtide

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9
Q

What is the mechanism of action of Enfuvirtide?

A

Prevents conformational change in gp41 that allows fusion of viral and host membranes

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10
Q

What is a major deterrent to use of Enfuvirtide?

A

Subcutaneous injection twice daily

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11
Q

What are side effects of Enfuviritide?

A

Subcutaneous seromas, discomfort at injection site

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12
Q

What agent(s) are in class of Nucleoside/nucleotide RT inhibitors (NRTIs)?

A 
Zidovudine (AZT)
DDI/D4T (didanosine, stavudine)
3TC/FTC (lamivudine, emtricitabine)
Abacavir (ABC)
Tenofovir (TDF)
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13
Q

What is method of action of NRTIs?

A

Analogs of nucleotide residues A, T, G, C competitively bind to active site of RT and cause chain-termination

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14
Q

What is a side effect of all NRTIs (but especially D4T/DDI)?

A

Mitochondrial toxicity

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15
Q

What is the clinical presentation of mitochondrial toxicity?

A 
Neuropathy
Myopathy
Lactic acidosis
Pancreatitis
Lipodystrophy/Lipoatrophy (Buffalo hump, facial wasting, no subcutaneous fat, visceral fat deposition)
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16
Q

What are side effects of AZT?

A

Anemia, leukopenia
Anorexia, nausea, diarrhea
Headache, fatige
Myositis, weakness

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17
Q

What population still receives AZT?

A

Pregnant women

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18
Q

What are side effects of DDI/D4T?

A

Mitochondrial toxicity
Pancreatitis
Peripheral neuropathy
Hepatitis

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19
Q

What are side effects of 3TC/FTC?

A

Not sure, always given with other drugs

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20
Q

What are most common NRTIs prescribed today?

A

Abacavir

Tenofovir

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21
Q

What are side effects of Abacavir?

A

Hypersensitivity reaction - appears flu-like

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22
Q

Should you rechallenge someone that had hypersensitivity reaction with Abacavir?

A

NO - can die

23
Q

What should you test for before you give Abacavir?

A

HLA B*5701 (if positive, predisposed to hypersensitivity reaction)

24
Q

What are side effects of Tenofovir?

A

Asthenia (general weakness)
Flatulence, abdominal pain
Impaired renal function (different dosing requirements or don’t give to someone with impaired renal function)

25
Q

What agent(s) are in class of Non-nucleoside RT inhibitors (NNRTIs)?

A

Nevirapine
Efavirenz
Etravirine
Rilpivirine

26
Q

What is the mechanism of action of NNRTIs?

A

Binds at site near but distinct from catalytic site of RT enzyme and inhibits functionality

27
Q

What are side effects of Nevirapine?

A

Rash, can progress to Stevens-Johnson
Severe hepatotoxicity
Potent induced of CyP450

28
Q

Who should not receive Nevirapine?

A

Women with CD4 >250, Men with CD4 >400

Greater risk of hepatotoxicity

29
Q

What are side effects of Efavirenz?

A 
CNS: Insomnia, vivid dreams, difficulty concentrating, hallucinations/psychosis
Rash, hepatotoxicity
False-positive cannabinoid test
Teratogenic
CyP450 interactions
30
Q

What are side effects of Etravirine?

A

Rash
Nausea
CyP450 interactions

31
Q

What are side effects of Rilpivirine?

A

Insomnia (less than Efavirenz)

Rash

32
Q

What should be taken into account when stopping NNRTI therapy?

A

Have long half life, leading to effective monotherapy when NNRTI-based triple drug regimen is stopped
Increases likelihood of resistance to NNRTIs!

33
Q

What agent(s) are in class of Integrase inhibitors?

A

Raltegravir
Elvitegravir
Dolutegravir

34
Q

What is the mechanism of action of Integrase inhibitors?

A

Inhibits catalytic activity of HIV-1 integrase, preventing integration of HIV DNA into host DNA

35
Q

What are side effects of Elvitegravir?

A

Decreases CrCl

Co-formulated with TDF (another nephrotoxic drug) so do NOT give to someone with impaired renal function

36
Q

What agent(s) are in class of Protease inhibitors?

A 
Ritonavir
Indinavir
Nelfinavir
Lopinavir/ritonavir
Atazanavir
Tipranavir
Darunavir
37
Q

What is mechanism of action of Protease inhibitors?

A

Prevent maturation of virions after they come out of host cells

38
Q

What is unique about Ritonavir?

A

Rarely used along as PI

Acts to “boost” levels of other PIs by inhibiting CyP450 3A4

39
Q

What are the side effects of Ritonavir?

A

GI: nausea, diarrhea, taste disturbance
Hyperglycemia
Hyperlipidemia
Fat maldistribution (lipoatrophy)

40
Q

What are the side effects of Indinavir?

A

Nephrolithiasis (kidney stones)

41
Q

What is unique about Nelfinavir?

A

Doesn’t require boost by Ritonavir

42
Q

What is unique about Lopinavir?

A

Coformulated with Ritonavir, cannot achieve effective levels on its own

43
Q

What are side effects of Atazanavir?

A 
Lipid-sparing
Asymptomatic hyperbilirubinemia (jaundice without other symptoms)
44
Q

What are side effects of Tipranavir?

A

Rash
Hepatotoxicity
Rare intracranial hemorrhage

45
Q

What are side effects of Darunavir?

A

Skin rash, Stevens-Johnson

Hepatotoxicity

46
Q

What are side effects of Nelfinavir?

A

Really bad diarrhea

47
Q

What is the preferred drug regimen for most patients?

A

2 NRTIs + 1 NNRTI, PI, or II

48
Q

What is the preferred dual-NRTI pairs?

A

TDF/FTC (tenofovir/emtricitabine)

49
Q

What are alternative dual-NRTI pairs?

A

ABC/3TC (abacavir/lamivudine) - risk of hypersensitivity rxn, possible risk of cardiovascular events
ZDV/3TC (AZT/lamivudine) - only really used for pregnant women

50
Q

What are the NNRTI based triple drug regimens?

A

EFV (efavirenz) + TDF/FTC

51
Q

What are the PI based triple drug regimens?

A

ATV/r (Atazanavir boosted with ritonavir) + TDF/FTC

DRV/r (Darunavir boosted with ritonavir) +TDF/FTC

52
Q

What are the Integrase inhibitor triple drug regimens?

A

DTG (dolutegravir) +ABC/3TC
DTG (dolutegravir) + TDF/FTC
EVG (elvitegravir)/COBI/TDF/FTC = all coformulated together as Stribild
RAL (raltegravir) + TDF/FTC

53
Q

What is an indication of therapy success?

A

Rapid viral load reduction (>1 log 10 decrease in 1-4 months)

54
Q

What do you do when you have treatment failure and patient is adherent?

A

Test for resistance while on failing regimen

Genotypic and phenotypic testing

Parasitology/Virology (19 decks)

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