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MHD2/Pharm Block 5 > HIV drugs > Flashcards

HIV drugs Flashcards

1
Q

What CD4 counts are associated with opportunistic infection?

A

Less than 500 cells/mm3, especially less than 200 cells/mm3​

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2
Q

What is the purpose of periodic CD4 cell counts throughout HIV infection?

A

Assessment of:

1) Immunologic status
2) Risk of opportunistic infections
3) Need for ART
4) Response to ART

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3
Q

Goals of ART

A
  1. Suppress viral load to reduce risk of disease progression
  2. Restore/preserve immunologic function
  3. Improve quality of life
  4. Reduce HIV-related morbidity and mortality
  5. Prevent HIV transmission
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4
Q

What are the 2 different PCR tests used to assess HIV status?

A

1) Viral load
2) Resistance testing

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5
Q

When are the appropriate times for HIV resistance testing?

A

Before initiating ART and after ART fails

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6
Q

When is the recommended time to begin ART?

A

Recommended for all HIV-infected individuals regardless of CD4 T cell count

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7
Q

What are the major drug classes used to treat HIV?

A
  1. NRTIs
  2. NNRTIs
  3. PI
  4. Integrase inhibitors
  5. Fusion inhibitors
  6. CCR5 antagonists
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8
Q

What is the difference between HIV 1 and HIV 2

A

HIV 1 is more common

HIV 2 is endemic to west Africa, has a longer asymptomatic stage and lower viral loads and mortality

Consider HIV 2 if patient presents with HIV-like symptoms but has negative serology for HIV 1

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9
Q

List the NRTIs

A

Mnemonic: LASTED Z

  • Lamivudine
  • Abacavir
  • Stavudine
  • Tenofovir
  • Emtricitabine
  • Didanosine
  • Zidovudine
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10
Q

Mechanism of action of NRTIs

A

Nucleoside (and nucleotide, tenofovir) analogs without a 3’-OH group compete with native nucleotides and cause chain termination during viral DNA synthesis

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11
Q

Which NRTI is associated with food restrictions

A

Didanosine has Dining restrictions

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12
Q

Does resistance easily develop against NRTIs?

A

No. Resistance to NRTIs requires 3 or 4 codon substitutions, which is unlikely to occur. Much less resistance is seen to NRTIs than NNRTIs and PIs

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13
Q

What is a naive patient?

A

Patients not previously treated with ART are considered to be naive

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14
Q

What is the major adverse effect of NRTIs, and which are specifically involved?

A

Lactic acidosis-hepatic steatosis syndrome

Didanosine > stavudine > zidovudine

Inhibition of DNA polymerase gamma inhibits mitochondrial DNA and oxidative phosphorylation, thus decreasing ATP production and leads to production of lactose

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15
Q

What must be considered in treating HIV patients that are also HBV+ with NRTIs?

A

HBV flare: discontinuation of certain NRTIs can increase HBV titer

Emtricitabine, Lamivudine, tenofovir

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16
Q

Mnemonic for NRTI side effects

A

The San Diego Zoo MIghT LET HepBs in

Mitochondrial effects: S, D, Z

HBV flare: L, E, T

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17
Q

What FDA-approved NRTIs are currently used?

A

Abacavir is used for combo therapy for HIV1

Zidovudine is used for combo therapy for HIV1 and 2, for exposure prophylaxis, and in pregnancy

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18
Q

What is the major adverse effect and contraindication for abacavir?

A

Patients with HLA-B5701 will have a hypersensitivity reaction which can be fatal

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19
Q

Adverse effects of zidovudine?

A

Bone marrow toxicity: anemia and neutropenia

For this reason, do not use zidovudine with myelosuppressive drugs like ganciclovir and ribavirin

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20
Q

What drug is antagonistic to zidovudine?

A

Stavudine is antagonistic to zidovudine, do not coadminister

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21
Q

What are the NNRTIs?

A

Mnemonic: NERD E

  • Nevirapine
  • Efavirenz
  • Rilpivirine
  • Delavirdine
  • Etravirine
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22
Q

Mechanism of action for NNRTIs

A

Noncompetitive inhibition of reverse transcriptase reduces enzyme activity (allosteric inhibition)

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23
Q

Describe the absorption and metabolism of NNRTIs

A

Rapidly absorbed and metabolized by hepatic CYPs, which can lead to several drug interactions

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24
Q

Why are NNRTIs used if resistance rapidly develops?

A

They are used in combo (never monotherapy) in order to reserve the use of protease inhibitors for later use, thus avoiding the PI adverse effects

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25
Q

What are the major adverse effects of efavirenz?

A

Drug interactions with CYP: efavirenz is a CYP inducer, so it lowers PI concentration, methadone concentration

Birth defects (contraindicated in 1st trimester, those planning to conceive)

CNS effects: vivid dreams

26
Q

When is nevirapine used instead of efavirenz?

A

Treatment of HIV1+ naive women with pretreatment CD4 below 250, and men with CD4 below 400

With higher CD4 levels, there is an increased risk for hepatotoxicity

27
Q

What drug interactions occur with nevirapine?

A

Nevirapine is a CYP3A4 inducer, just like efavirenz. It decreases the serum concentration of methadone, PIs

28
Q

Which drugs are protease inhibitors?

A

Mnemonic: SAINT FDR

All end in “-navir”

  • Saquinavir
  • Atazanavir
  • Indinavir
  • Nelfinavir
  • Tipranavir
  • Fosamprenavir
  • Darunavir
  • Ritonavir
29
Q

Mecahnism of action of PIs

A

Inhibition of HIV aspartyl protease, thus blocking the processing of viral proteins and preventing virus maturation

30
Q

What are the major adverse effects associated with protease inhibitors?

A

Metabolic syndrome

Lipodystrophy

Drug interactions: PIs are CYP substrates and inhibitors

31
Q

What do Rifampin, Phenobarbitol and St. Johns Wart have in common?

A

Strong inducers of CYP3A4, which decrease the levels of PI

32
Q

Quinidine, ergotamine, midazolam, and warfarin all have the same side effect. What is it?

A

All are CYP3A4 substrates, which increase the levels of PI

33
Q

Ritonavir is not effective for HIV therapy because it is limited by adverse effects. Why is it still used frequently for HIV patients?

A

Ritonavir is used at low doses to boost other PIs effects by inhibiting CYP3A4. This allows lower doses of PIs to be effective.

34
Q

What is metabolic syndrome?

A

Cluster of metabolic risk factors (hyperlipidemia, hypertriglyceridemia, decreased HDL/ncreased LDL, hypertension, hyperglycemia)

Increases risk for CVD, stroke, diabetes

35
Q

Which statins are safe to use with ART?

A

Pravastatin and fluvastatin are safe to use with ART because they are not substrates of CYP3A4

36
Q

Which drugs are the integrase inhibitors?

A

All contain “-tegravir”

  • Raltegravir
  • Elvitegravir
  • Dolutegravir
37
Q

What is the mechanism of action of integrase inhibitors?

A

Blocks insertion of reverse transcribed viral DNA into the host DNA by binding the Mg++

38
Q

Onset and duration of action of integrase inhibitors

A

Twice daily dosing following high fat meal with half-life of 9 hours

39
Q

What combination with integrase inhibitors is effective at reducing viral load?

A

Integrase inhibitors are used effectively in combo with a protease inhibitor and a NRTI

40
Q

Which integrase inhibitor has the shortest half life? longest?

A

Elvitegravir is the shortest (3h if not boosted, 9h boosted)

Dolutegravir has the longest (12-15h)

41
Q

What is the mechanism of action of maraviroc?

A

small molecule CCR5 antagonist

prevents virus to attach to surface of CD4 T cells (prevents CCR5-gp120 interaction)

42
Q

What is the mechanism of action of enfuvirtide?

A

Fusion inhibitor

Blocks gp41 and prevents interaction required for membrane fusion within the host cell

43
Q

Contraindication for enfuvirtide therapy

A

Don’t use if patient has a known hypersensitivity

44
Q

Resistance mechanism for maraviroc

A

Mutation of CCR5 binding AA sequence in the gp120 protein

CXCR40 tropic virus (check using Trofile assay)

45
Q

Drug interactions of maraviroc

A

CYP substrate, so concentration is altered by rifampins, ritonavir

46
Q

What ART drug should be avoided for pregnant patients?

A

Efavirenz

47
Q

A patient tests positive for HLA-B5701. What drug is contraindicated?

A

Abacavir

48
Q

Which ART drug is affected by both gender and pretreatment CD4 count?

A

Nevirapine

49
Q

How is TB treated for patients receiving ART?

A

Rifabutin is used instead of rifampin to avoid interaction with PIs and NNRTIs

Exception: Efavirenz is less affected by Rifampin than other NNRTIs

Patient will require monitoring and dose adjustments

50
Q

What are the preferred combinations for ART in naive patients?

A

2 NRTIs and either 1 NNRTI or 1 PI

Examples:

Tenofovir + Emtricitabine + Efavirenz

Abacavir + Lamivudine + Atazanavir (+ritonavir booster)

51
Q

Reasons for HAART treatment failure

A

Virologic suppression failure

Immunologic failure

Drug resistance

52
Q

Do triple NRTI regimens work?

A

Not indicated. High rate of nonresponse in naive patients

53
Q

Rationale for not combining atazanavir + indinavir

A

Can cause hyperbilirubinemia

54
Q

Rationale for not combining didanosine + stavudine

A

High incidence of toxicity, lactic acidosis

“STeVe DIeD”

55
Q

Rationale for not using 2 NNRTIs in combo

A

Combination (EFV + NVP) has more adverse effects than separate

EFV and NVP both reduce concentrations of ETV

56
Q

Rationale for not combining Emtricitabine + Lamivudine

A

They have similar resistance profiles

“Resist LAMe EMTs”

57
Q

What is the rationale for not combining etravirine + unboosted PI

A

Induced PI metabolism decreases concentrations, effectivity

58
Q

Rationale for not combining Etravirine + boosted ATV, FPV or TPV

A

Induced PI metabolism, decreases concentrations, effectivity

59
Q

Rationale for not using Nevirapine in naive women with CD4>250, men CD4>400

A

High incidence of hepatotoxicity when CD4 counts are higher

60
Q

Rationale for not combining Stavudine and Zidovudine

A

They are antagonistic

“STeVe hateZ ants”

61
Q

How was one man cured of HIV?

A

He received a stem cell transplantation from someone with a CCR5 mutation

MHD2/Pharm Block 5 (5 decks)

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