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MID II > HIV antiretroviral therapy > Flashcards

HIV antiretroviral therapy Flashcards

1
Q

What is HAART?

A

Highly Active AntiRetroviral Therapy

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2
Q

What are the 6 classes of antiretrovirals?

A
  • Nucleos(t)ide reverse transcriptase inhibitors (NRTIs)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • Protease Inhibitors (PIs)
  • Fusion inhibitor
  • CCR5 antagonist
  • Integrase inhibitors
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3
Q

Whats the difference between Nucleoside and Nucleotide

A

Nucleoside = needs to be phosphorylated
Nucleotide = already diphosphorylated

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4
Q

What is the process of HIV infectino of CD4 cell?

A

HIV binds the CD4 receptor –> glycoprotein capsid is released during fusion –> RNA is reverse transcribed to DNA –> DNA is integrated from cytoplasm into host nucleus (this is why it has latency, bc it integrates in the the host genome of CD4+ cell) –> at time of reactivation, uses normal host machinery to make RNA –> new RNA is integrated into virion making viral particles (catalyzed by the enzyme protease)

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5
Q

Which steps can antiretrivirals inhibit?

A

Binding to the CD4 receptor

Synthesis of viral DNA via Reverse Transcriptase

Integration into host chromosomal DNA

Assembly of virus and budding from the cell

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6
Q

How do NRTI’s work?

A

Compete with host nucleotides- competitive inhibitor, chain terminators

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7
Q

What are the NTRIs?

A

Nucleoside: block replication with “ZEAL”
Zidovudine = AZT
Emtricitabine
Abacavir
Lamivudine

Nucelotide:
Tenofovir

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8
Q

What are the side effects of nucleoside RTI’s?

A

Lactic acidosis, neuropathy

Abacavir = hypersensivity syndrome

Anemia = AZT

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9
Q

What are the side effects of nucleotide RTIs?

A

Nephrotoxicity

Fanconi’s syndrome = kidney

Bone mineralization

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10
Q

What’s the mechanism of action of NNRTIs?

A

Inhibit RT through binding the enzyme near the active site & locking it in an inactive conformation

Active against HIV-1 only

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11
Q

What are the NNRTIs?

A

ENE

Efiravenz (1G)

Nevirapine (1G)

Etravirine (2G)

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12
Q

What are the side effects of NNRTIs?

A

1st gen = susceptible to resistance, neuro, teratogen “Efavirenz effs with your dreams and yo baby”

All have rash, liver, DDI (CYP3A4)

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13
Q

How do proteas inhibitors work?

A

Bind active iste of protease, prevent cleaving of precursor proteins for important enzymes (gag and gag-pol)

Leads to production of virions that are incomplete and noninfectious

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14
Q

What are the PI’s

A

“messes with your LARD”

Lopinavir

Atazanavir

Ritonavir

Darunavir

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15
Q

What are the side effects of PIs?

A

GI, dyslipidemia, atherosclerosis, DDI (CYP3A4)

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16
Q

Why is ritonavir always included when administering other protease inhibitors?

A

Inhibits CYP3A4, making it a great “booster” to increase conc of other drugs

17
Q

Which drugs have higher barriers to resistance? Lower barrier?

A

Protease inhibitors - you need accumulation of several mutations

NNRIs: one mutation can lead to resistance

18
Q

How do fusion inhibitors work?

Which drug is it?

What is the side effect?

A

Prevents entry by binding to the glycoprotein on the viral envelope - binds gp41 envelope glycoprotein

Enfuvirtide
“Enfelope” binding

Injectible only

Injection site effects

Very potent/ salvage therapy for those who have multidrug resistance HIV

19
Q

What is the CCR5 antagonist?

What is its mechanism?

A

Maraviroc
“Rocblocks CCR5”

Prevents entry by binding to the chemokine coreceptor on the host CD4+ cell

Active against CCR5 tropic virus only

20
Q

How do integrase inhibitors work?

A

Inhibit DNA integration into genome

21
Q

What are the 2 integrase inhibitors?

A

Raltegravir

Elvitegravir (combo with cobicistat-booster, tenofovir-NRTI, and emtricatabine- NRTI)

”-gravir” are integrase inhibitors

22
Q

What are the side effects of integrase inhibitors?

A

Low barrier to resistance, cross resistance in the class, take it 2x/day, headache, rash

23
Q

What are the 2 boosters?

A

Ritonavir: early protease inhibitor, used to boost other PIs. can cause GI discomfort and dyslipidemia

Cobicistat: not an antiretroviral agent, coformulated with integrase inhibitor elvitegravir; can cause renal dysfunciton

Both are potent inhibitors of CYP3A4

24
Q

Which drugs treat both HIV and Hep B?

A

Lamivudine

Emtrictabine

25
Q

What is the backbone for HAART?

A

tenofovir

Emtricitabine

26
Q

What are the three first line antiretroviral therapy options?

A

2NRTI + one of the following:

1NNRTI

1PI/r

1 INSTI

27
Q

What are the goals of ART?

A

Decrease viral load

Rise CD4+ count

Decrease in HIV associated morbidity and mortality

28
Q

What is the risk of percutaneous exposure for HIV?

MID II (22 decks)

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