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Pharmacology > HIV Therapy > Flashcards

HIV Therapy Flashcards

1
Q

Does ART cure HIV?

A

NO - it only keeps the viral load low

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2
Q

What is the major target cell of HIV?

A

CD4+ T cells

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3
Q

What is the normal CD4 T cell count?

A

800-1500 cells/mm3

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4
Q

At what level of CD4 cells are patients at increased risk for infections?

A

Less than 500 cells/mm3

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5
Q

What is used to determine the viral load in HIV?

A

PCR-based load assessment testing

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6
Q

When do you start ART?

A

ART is recommended for all HIV-infected individuals, regardless of CD4 T lymphocyte cell count, to reduce the morbidity and mortality associated with HIV infection

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7
Q

Where is HIV-2 endemic?

A

West Africa

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8
Q

What class are these drugs?

  1. Abacavir
  2. Didanosine
  3. Emtricitabine
  4. Lamivudine
  5. Stavudine
  6. Tenofovir
  7. Zidovudine
A

Nucleoside/Nucleotide RT Inhibitors

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9
Q

NRTI MOA

A

They are nucleotide or nucleoside analogs that will compete for incorporation into viral genome and when they are they terminate the DNA strand

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10
Q

What are naive patients?

A

Patients not previously treated with ART are considered to be “naïve”

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11
Q

NRTI SE

A

Inhibit DNA polymerase γ, blocking production of mtDNA and inhibiting oxydative phosphorylation complexes. This promotes production of cytosolic lactate, and may induce lactic acidosis-hepatic steatosis syndrome.

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12
Q

Which of the NRTIs can cause lactic-acidosis-hepatic steatosis syndrome?

A
  • Didanosine
  • Stavudine
  • Zidovudine
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13
Q

What is the main DNA polymerase in humans?

A

DNA polymerase α

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14
Q

What can be a complication of NRTI discontinuation?

A

Discontinuation of agents that have anti-HBV

activity is associated with increase in HBV titer - HBV flare

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15
Q

Abacavir Contraindications

A

HLA-B 5701+ patients - can cause hypersensitivity that can be lethal

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16
Q

Zidovudine Contraindications

A

Stavudine antagonistic - not for co-administration

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17
Q

Which NRTIs are preferred for naive patients?

A
  • Emtractitabine

- Tenofovir

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18
Q

What are NNRTIs?

A

Nonnucleotide RT Inhibitors

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19
Q

What drug class are these?

  1. Delavirdine
  2. Efavirenz
  3. Etravirine
  4. Nevirapine
  5. Rilpivirine
A

NNRTIs

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20
Q

NNRTI MOA

A

Noncompetitive inhibitors bind to RT and induce a conformational change that greatly reduces enzyme activity

21
Q

Are NRTIs and NNRTIs used as mono therapies?

A

No

22
Q

NNRTI SE

A

CYP450 interaction

23
Q

Efavirenz Contraindications

A

1st trimester pregnancy or in women planning to conceive

24
Q

Nevirapine SE

A

Severe hepatotoxicity

25
Q

Nevirapine Contraindications

A

Women with pretreatment CD4 greater than 250 cells/mm and men with CD4 greater than 400 cells/mm

26
Q

What drug class do the following drugs belong to?

  1. Ritonavir
  2. Fosamprenavir
  3. Atazanavir
  4. Indinavir
  5. Nelfinavir
  6. Saquinavir
  7. Tipranavir
  8. Darunavir
A

Protease Inhibitors

27
Q

Protease Inhibitor MOA

A

PIs inhibit HIV aspartyl protease, block

processing of viral proteins required to produce a mature viral particle.

28
Q

How effective are protease inhibitors?

A

Highly effective in the majority of patients when used in combination therapy.

29
Q

What are some drugs that should not be administered alongside protein inhibitors due to CYP metabolism?

A
  • Quinidine
  • Rifampin
  • Warfarin
  • St. John’s Wart
30
Q

Ritonavir SE

A

Paresthesia - not well tolerated at high doses that are effective

31
Q

Why is ritonavir used in ART even though it cannot be tolerated at the needed doses?

A

Ritonavir is a potent CYP inhibitor that enhances the half life of other protease inhibitors and allows for reduced dose and frequency

32
Q

What can PIs induce?

A

Metabolic Syndrome

33
Q

What are the features of metabolic syndrome?

A
  • Hyperlipidemia
  • Diabetes
  • Central Obesity
  • Atherosclerosis
34
Q

What dyslipidemia drugs should be avoided in patients on protease inhibitors?

A

Statins that are CYP3A4 substrates like pravastatin and fluvastatin

35
Q

Integrase Inhibitor MOA

A

Inhibits integrase enzyme of HIV that leads to the integration of viral DNA into the host DNA

36
Q

Raltegravir MOA

A

Blocks the insertion of reverse-transcribed

viral DNA into the host DNA by binding the Mg++ cofactors required for the strand transfer - integrate inhibitor

37
Q

What drug class are:

  • elvitegravir
  • dolutegravir
A

Integrase Inhibitor

38
Q

Enfuvirtide MOA

A

This peptide binds to HIV surface glycoprotein

gp41 to block conformation required for membrane fusion with host cell - fusion inhibitor

39
Q

What is the route of administration of enfurvitide?

A

Injection

40
Q

Maraviroc MOA

A

Small molecule slowly-reversible antagonist of

the CCR5 interaction with gp120, blocks CCR5-tropic HIV-1 entry

41
Q

What is the problem of rifampin co-administered with ART?

A

Rifampin induces CYP enzymes and reduces exposure to PIs and NNRTIs

42
Q

What is the general recommendation for starting ART?

A
  1. 1 NNRTI + 2 NRTI

OR

  1. 1 PI + 2 NRTI
43
Q

What is the preferred NNRTI?

A

Efavirenz

44
Q

What is the preferred PI combination?

A

Atazanavir + Rifonavir

45
Q

Virology Suppression Failure

A

The inability to achieve or maintain suppression of viral replication to levels below the limit of detection

46
Q

Immunologic Failure

A

The inability to achieve and maintain an adequate CD4 T-cell response despite virologic suppression

47
Q

Should ART ever be mono therapy?

A

NO

48
Q

A 29 year-old male was previously diagnosed with M. tuberculosis infection and rifampin treatment was initiated. In a follow up exam, lab results reveal
the patient to be infected with HIV, and lab results are as follows: CD4+ count = 460 cells/mm3
viral load = 41,000 copies/ml resistance testing = HIV1
Which of the following treatment regimens would be a recommended option, if any?

A. efavirenz, tenofovir, and emtricitabine
B. Nevirapine, tenofovir, and emtricitabine
C. Atazanavir, darunavir, and tipranavir
D. Didanosine, abacavir, and lamivudine
E. None of the above

A

A. efavirenz, tenofovir, and emtricitabine

Pharmacology (74 decks)

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