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What is the main drawback to Lamivudine?
Resistance increases with every year of therapy
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What drugs would you use for Lamivudine resistant strains of HBV?
Adefovir or Entecavir
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What are the main issues with Oral HBV drugs?
Resistance and exacerbation of disease upon D/C
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What dictates the treatment in HCV?
Genotype
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Which is the most difficult genotype to treat in HCV?
G1 = found mainly in the US
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What are the treatment indications for HCV?
- Positive HCV antibodies for > 6 months
- Positive HCV RNA
- Elevated serum aminotransferase levels
- Histologic evidence of inflammation (liver biopsy)
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How long are usual HCV treatments?
12-48 weeks (depending on genotype)
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What is the dosing for Peginterferon-α2a (Pegasys)
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What is the dosing for – Peginterferon-α2b (PegIntron)?
- 1.5 mg/kg
- Once weekly SUBQ
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Peginterferons always come in combination with what other drug for the treatment of HCV?
Ribavirin
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What is the dosing for Ribavirin
- < 75 kg = 1000mg
- > 75 kg = 1200mg
- Weight-based daily PO
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What are the direct acting agents for treatment of HCV?
- 1st Gen:
- Boceprevir
- Telaprevir
- 2nd Gen:
- Sofosbuvir
- Simeprevir
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What is the dose for Boceprevir in HCV treatment?
- 800mg PO TID
- Requires 4 week lead in period with Interferon + Ribavirin
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What is the dose for Telaprevir in HCV treatment?
- 1125mg PO BID
- Must be given with Interferon + Ribavirin
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What is the dose for Sofosbuvir in HCV treatment?
400mg PO Daily
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What is the dose for Simeprevir in HCV treatment?
150mg PO Daily
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What is the MOA of direct acting agents used for HCV?
Block viral replication at specific region of HCV genome
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What are the advantages of second generation Direct acting agents over 1st gen in treatment of HCV?
- 2nd gen are QD (vs. BID/TID)
- 2nd gen do not have to be given with Ribavirin and Interferon
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What are the CIs for Interferon Alpha?
- Current or HX of psychosis
- Severe depression
- Neutro/thrombocytopenia
- Symptomatic heart disease
- Decompensated cirrhosis
- Uncontrolled seizures
- Organ transplantation
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What are the CIs for Ribavirin?
- Pregnancy (Category X)
- Risk of pregnancy
- End-stage renal failure
- Anemia
- Hemoglobinopathies
- Severe heart disease
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If a patient is interferon eligible, has Genotype 1 and is treatment Naïve, what would you treat them with?
Sofosbuvir, Ribavirin, and IFN weekly x 12 weeks
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If a patient is interferon INeligible, has Genotype 1 and is treatment Naïve, what would you treat them with?
- Sofosbuvir + Simeprevir + Ribavirin x 12 weeks
- OR
- Sofosbuvir + Ribavirin x 24 weeks
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Do NOT treat decompensated cirrhosis caused by HCV genotype 1 with what two drugs?
Interferon or Simeprevir
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How should you treat HCV genotype 2, treatment naïve patients?
Sofosbuvir + Ribavirin for 12 weeks
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What should you not use to treat HCV genotype 2, treatment naïve patients?
- Monotherapy with any drug
- Interferon + Ribavirin for 24 weeks
- Telaprevir, Boceprevir, or Simeprevir based regimens
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