MI: Antivirals Pt.2

Question 1

Describe pre-emptive therapy for CMV

Answer 1

Used for HSCT transplant patients

• Monitoring with weekly blood CMV PCR
• Gancicolvir/valganciclovir initiated when viral load reaches certain threshold e.g. 1000 c/ml
• This threshold is a reached a week before the onset of disease

Question 2

What is the mechanims of action of ganciclovir? How is it activated?

Answer 2

• Nucleoside analogue that inhibits viral DNA polymerase and also halts chain elongation
• Activated by viral UL97 kinase

Question 3

What is the pro-drug of ganciclovir?

Answer 3

Valganciclovir (given PO)

Question 4

What are 2nd line treatments for CMV?

Answer 4

1. Foscarnet (IV/intravitreal)
2. Cidofovir
3. Maribavir

Question 5

What is the mechanism of action of foscarnet?

Answer 5

• Non-competitive inhibitor of viral DNA polymerase

NOTE: does not require activation

Question 6

What is a major side-effect of foscarnet?

Answer 6

Nephrotoxicity

Question 7

What is the mechanism of action of cidofovir?

Answer 7

Cytidine analogue that competitively inhibits viral DNA synthesis

NOTE: does not require activation

Question 8

What is a major side-effect of cidofovir?

Answer 8

Nephrotoxicity (requires hydration and probenecid)

Question 9

How is CMV pneumonitis treated?

Answer 9

Ganciclovir with IVIG

Question 10

What are three strategies for the treatment of CMV in transplant patients?

Answer 10

1. TREAT established disease
2. PROPHYLAXIS (mainly in solid organ transplant patients)
3. PRE-EMPTIVE THERAPY (for bone marrow transplant patients)

Question 11

What is the mechanism of action of maribavir?

Answer 11

Inhibits viral kinase UL97

Effective in vitro, currently undergoing clinical trials

Question 12

What is the mechanism of action of letermovir? What is it used for?

Answer 12

• CMV DNA terminase inhibitor
• Used for CMV prophylaxis in IgG-positive HSCT patients

Question 13

In which cells does EBV cause continuous low-grade viral replication?

Answer 13

B cells

Question 14

What is post-transplant lymphoproliferative disease (PTLD)?

Answer 14

• Polyclonal expansion of B cells associated with immunosuppression used in organ transplant
• This is due to breakdown of immunosurveillance keeping the B cells and EBV in check
• This predisposes to lymphoma

Question 15

How is post-transplant lymphoproliferative disease diagnosed and treated?

Answer 15

Diagnosis: EBV viral load >10^5 c/ml in blood + positive biopsy

Treatment

• Reduce immunosuppression
• Rituximab (anti-CD20)

Question 16

What are the roles of haemagglutinin and neuraminidase in the influenza virus?

Answer 16

• Haemagglutinin - mediates viral binding and entry into target cell
• Neuraminidase - allows release of progeny virus particles from the host cell to infect neighbouring cells

Question 17

Name two examples of neuraminidase inhibitors.

Answer 17

• Oseltamivir (Tamiflu) - oral
• Zanamivir (Relenza) - dry powder