Anti-retroviral

Question 1

General Guideline for HIV management in Treatment of Naive patient:

Answer 1

Add Tenofovir/Emtricitabine to ALL

Truvada=Tenofovir/Emtricitabine

RTV=los-dose ritonavir as boosting agent

• NNRTI-based backbone
  
  • Efavirenz (alternative choice)
• PI-based backbone
  
  • Darunavir + RTV
    
    • first choice
  • Atazanavir + RTV
    
    • alternative choice
• INSTI-based backbone:
  
  • Dolutegravir
    
    • first choice
  • Raltegravir
    
    • first choice

Pregnant Patient:

• Lopinavir/ritonavir +
  
  • zidovudine/lamivudine
  • abacavir/lamivudine
  • tenfovoir/emtricitabine

Question 2

5 classes of HIV drugs:

Answer 2

• Drugs that inhibit enzymes need for HIV replication:
  
  • Reverse Transcriptase Inhibitors:
    
    • Nucleoside (NRTIs)
      
      • aka nukes
      • block reverse transcription
    • Non-Nucleoside (NNRTIs)
      
      • aka non-nuke
      • block reverse transcription
  • Protease Inhibitors (PI)
    
    • block budding
  • Integrase Strand Transfer Inhibitors (ISTI)
    
    • block integration
• Drugs that inhibit viral entry into host cell:
  
  • CCR5 antagonists
    
    • block binding
  • Fusion Inhibitor
    
    • block fusion and uncoating

Question 3

HAART

Answer 3

Combination of 3 drugs:

• 2 nukes +
  
  • 1 PI
  • 1 Non-nuke
  • 1 integrase I

Question 4

Preferred Regimen for Treatment of Naive Patients:

Answer 4

All have Tenofovir/emtricitabine=Truvada

• Efavirenz
• Atazanavir (boosted)
  
  • RTV=boost
• Darunavir (boosted)
  
  • RTV=boost
• Raltegravir

Question 5

NRTIs: General Features

• MOA
• PK
• side effects

Answer 5

• MOA:
  
  • nucleoside/tide analog
  • require intracellular activation (phosphorylation)
  • Inhibit HIV-1 reverse transcriptase
    
    • decrease replication in infected cells
  • Incorporated into viral DNA causing early chain termination
• PK
  
  • not metabolized by CYPs
• Side effects:
  
  • cause lactic acidosis w/hepatic steatosis (rare but fatal)

Question 6

NRTIs: Drugs

Answer 6

• Emtricitabine
  
  • 1st line treatment of naive pt (+tenofovir DF)
  • well tolerated but hyperpigmentation of palms and soles
• Tenofovir Disoproxil Fumurate
  
  • 1st line for:
    
    • treatment of naive pt (+ emtricitabine)
    • HIV/HBV co-infected
• Abacavir & Lamivudine
  
  • alternate backbone

Question 7

NNRTIs: General Features

• MOA
• PK
• Side effects

Answer 7

• MOA:
  
  • Direct non-nucleoside inhibitors of HIV-1 reverse transcriptase
    
    • inhibit HIV-1 reverse transcriptase
      
      • decrease replication
    • Incorporate into viral DNA causing early chain termination
  • No used as monotherapy bc resistance develops rapidly
• PK
  
  • metabolized by hepatic CYPs
    
    • many DDIs
• Side effects:
  
  • Elevated Liver Function Enzymes
  • hypersensitivity reactions (Rash)

Question 8

NNRTIs: Drugs

Answer 8

• Efavirenz (most important)
  
  • 1st line NNRTI for treatment of naive
  • Side effects:
    
    • rash
    • diarrhea
    • insomnia
    • nightmares
    • dyslipidemia
    • tertogenecity
  • Pregnancy Category D
  • Substrate, inhibitor, & inducer of CYP3A4
• Rilpivirine
• Etravirine
• Nevirapine
• Delaviridine

Question 10

PIs: General

• MOA
• PK
• side effects

Answer 10

• MOA
  
  • prevent the HIV protease enzyme from cleaving the polypeptide (and structural proteins) into mature infectious particles
  • All PIs bind reversibly to active site of the enzyme
• PK
  
  • all extensively metabolized by CYP3A4
• Side effects:
  
  • Hyperlipidemia
  • Fat malditribution
  • Hyperglycemia
  • Insulin Resistance
  • Breast enlargement
    
    • except atazanavir

Question 11

PIs: Drugs

Answer 11

-navir

• Ritonavir
  
  • potent CYP3A4 inhibitor
  • Never administered alone
  • Used at low doses to “boost” plasma levels of other PIs
    
    • increase metabolism of other PIs
• Atazanavir
  
  • 1st line PI for treatment of naive
    
    • boosted with ritonavir
    • alternate choice
  • One of the most used
  • can cause changes in heart rythm=prolong PR
• Darunavir
  
  • 1st line PI for treatment of naive
    
    • boosted with RTV
    • first choice
  • Developed specifically for resistant HIV;
  • allergic to sulfa-dont give; similar to sulfa
  • one of the most used
• Lopinavir:
  
  • 1st line PI for treatment of naive pregnant women
    
    • boosted with RTV

Question 13

Rifampin

Answer 13

• Major TB drug
• Increases drug metabolizing enzymes
• Decrease the blood levels of NNRTIs and PIs
  
  • not therapeutic anymore
  • Subtherapeutic resistance

Question 14

ISTI: General:

-MOA