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Week 18 > Anti-retroviral > Flashcards

Flashcards in Anti-retroviral Deck (14)
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1

General Guideline for HIV management in Treatment of Naive patient:

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

2

5 classes of HIV drugs:

  • 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

3

HAART 

Combination of 3 drugs:

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

4

Preferred Regimen for Treatment of Naive Patients:

All have Tenofovir/emtricitabine=Truvada

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

5

NRTIs: General Features

-MOA

-PK

-side effects

  • 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)

6

NRTIs: Drugs

  • 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

7

NNRTIs: General Features

-MOA

-PK

-Side effects

  • 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)

8

NNRTIs: Drugs

  • 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

9

10

PIs: General

-MOA

-PK

-side effects

 

  • 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

11

PIs: Drugs

-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

12

13

Rifampin

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

14

ISTI: General:

-MOA