Antiviral Agents

Question 1

Aciclovir/Valaciclovir/famciclovir

Answer 1

• Guanosine (nucleoside) analogue which becomes incorporated into viral DNA and prevents elongation (chain terminator)
• It is specific to viral DNA because:
  1. Higher affinity to viral DNA than host cells DNA
  2. Requires viral enzyme, thymidine kinase, for activation
• Aciclovir is PO/IV, Valciclovir is PO with high bioavailability
• Adverse effects uncommon (neurotoxicity, nephrotoxicity)

Question 2

Foscarnet

Answer 2

• Non-competitive inhibitor of viral DNA polymerase
• Does not require activation by kinase enzyme
• Active against CMV and HSV
• Given by slow IV infusion, or by intravitreal implants (for CMV retinitis)
• Can be given for CMV infection where ganciclovir is contraindicated e.g. neutropenia
• Nephrotoxic, so drink plenty

Question 3

Cidofovir

Answer 3

• Cytidine (nucleotide) analogue - competitive inhibitor of viral DNA synthesis
• Effective against CMV and HSV
• Does not need activation by viral enzyme
• Indicated as 3rd line treatment for CMV in the immunocompromised
• IV infusion, or local cream
• Side-effects - nephrotoxic, so drink plenty and give with probenicid

Question 4

Ganciclovir

Answer 4

• Effective against CMV and HSV but mainly used for CMV
• Guanosine (nucleoside) analogue which prevents viral DNA synthesis
• Requires activation by UL97 viral enzyme
• Given IV (slow infusion)
• Side-effects include bone marrow suppression, neutropenia, hepatic and liver dysfunction

Indications

• CMV infection in immunocompromised
• Congenital CMV infection

Question 5

HSV encephalitis - treatment

Answer 5

IV aciclovir 10mg/kg TDS for 21 days

Question 6

HSV meningitis - treatment

Answer 6

• Treatment not usually indicated

- For the immunocompromised, give IV aciclovir for 3-4 days and PO aciclovir for 10 days