Anti-retrovirals

Question 1

“Old” Drug Classes

Answer 1

• Nucleoside Reverse Transcriptase Inhibitors
• Non-Nucleoside Reverse Transcriptase Inhibitors
• Protease Inhibitors

Question 2

“New” Drug Classes

Answer 2

• Fusion inhibitors
• Entry inhibitors
• Integrase inhibitors
• Attachment/post-attachment inhibitors

Question 3

NRTIs - Pyrmidines

Answer 3

• C analogs: Emtricitabine* (FTC), lamivudine

- T analogs: zidovudine, stavudine

Question 4

NRTIs - Purines

Answer 4

• G analogs: abacavir

- A analogs: tenofovir* (TDF –> TAF)

Question 5

NRTIs MOA, pharm/clin manifestations

Answer 5

• Nucleoside/tide analogs interfere with HIV viral RNA-dependent DNA polymerase (inhibition of viral replication)
• Induce mitochondrial dysfunction
• Clinical manifestations: neuropathy, myopathy, CMP, pancreatitis, hepatic steatosis, lactic acidosis

Question 6

NRTIs ADRs (thymine, cytosine, adenine, guanine analogs)

Answer 6

• Zidovudine (thymine): anemia/neutropenia, hyperpigmentation of oral mucosa/nailbeds
• Stavudine (thymine): pancreatitis, peripheral neuropathy
• Emtricitabine (cytosine): +HBV activity
• Tenofovir (adenine): +HBV activity
• Abacavir (guanine): hypersensitivity rxn - fever, rash, fatigue, GI, respiratory sxs; HLA B*5701

Question 7

NNRTIs - 1st gen (ADRs)

Answer 7

• Nevirapine (HTX and severe rash)

- Efavirenz: teratogenic in monkeys, rash common, drug interactions

Question 8

NNRTIs - 2nd gen, MOA, ADRs

Answer 8

• Etravirine
• Doravirine
• Rilpivirine* (RPV)
• MOA: directly binds reverse transcriptase, blocks HIV polymerase acitivites/replication
• ADRs: severe rash may occur (SJS)

Question 9

Protease Inhibitors, MOA

Answer 9

• Darunavir*

- MOA: bind to HIV protease, does not allow HIV to be infectious (formation of immature, noninfectious viral particles)

Question 10

PI Pharmacology

Answer 10

• Ritonavir and cobicistat are used to increase concentration of other PIs (decrease dosage frequency)
• Meds to watch: statins, roids, PDE5 inhib, antiplatelets/anticoags, abx, CCBs
• 3A4 interactions

Question 11

PI ADRs

Answer 11

• NVD
• Hyperglycemia, insulin resistance, hyperlipidemia
• HTX
• Darunavir is a sulfonylarylamine*

Question 12

INSTIs, MOA, ADRs

Answer 12

• tegravir drugs
• MOA: inhibits integrase, prevents integration of proviral gene into human DNA
• ADRs: NVD, abd pain MC

Question 13

Fusion inhibitors, MOA

Answer 13

• Enfuvirtide

- MOA: binds to gp41 subunit of the envelope glycoprotein

Question 14

Entry inhibitors, MOA

Answer 14

• Maraviroc

- MOA: CCR5 antagonist -> binds to chemokine coreceptor located on CD4 cells -> cell entry blocked

Question 15

Post-attachment inhibitors, MOA

Answer 15

• Ibalizumab-uiyk*
• MOA: recombinant humanized CD4 directed monoclonal ab that blocks entry of HIV into CD4 cells
• Used only in MDR-HIV

Question 16

Attachment inhibitors, MOA

Answer 16

• Fostemsavir
• MOA: gp120
• Used only in MDR-HIV