MI: Antivirals Pt.3

Question 1

What is the most common cause of bronchiolitis?

Answer 1

RSV

Question 2

List three treatments for bronchiolitis and their mechanism of action

Answer 2

• Ribavirin - guanosine analogue
• IVIG - often used as adjunct to treatment of viral pneumonitis in immunocompromised patients
• Palivizumab - monoclonal antibody against RSV F (fusion) protein. Used for prophylaxis against serious infection in high-risk infants (e.g. BPD)

No real drug against active RSV.

Question 3

What drug is used to treat monkeypox? When is it used?

Answer 3

Tecoviromat

• Severe disease - >100 lesions, encephalitis, sepsis
• Anatomical concern - eye lesions, dysphagia, urinary retention
• High-risk patient - immunocompromised, pregnant, paediatric

Question 4

What is BK virus? What diseases can it cause and in which groups of patients?

Answer 4

A ubiquitous virus that is asymptomatic

• Can cause haemorrhagic cystitis in HSCT patients
• Can cause BK nephritis and ureteric stenosis in renal transplant patients

Question 5

Outline the treatment of BK haemorrhagic cystitis.

Answer 5

• Bladder washouts
• Reduce immunosuppression
• Cidofovir IV (may consider intravesical)

Question 6

Outline the treatment of BK nephropathy.

Answer 6

• Reduce immunosuppression
• IVIG

NOTE: cidofovir cannot be used because it is nephrotoxic

Question 7

In which subgroup of patients is adenovirus a major issue?

Answer 7

Paediatric transplant patients - can cause disseminated disease

Adenovirus is very common and usually causes self-limiting respiratory, GI, and conjunctival infection

Question 8

Outline the treatment of adenovirus infection in transplant patients.

Answer 8

• Cidofovir IV
• IVIG

Question 9

Describe how cellular immunotherapy may be used to treat viral infection

Answer 9

Patient CD8 T cells are isolated then exposed to specific viral antigens, and then reinfused

Now increasingly used as second line therapy for a range of viral infections in transplant recipients.

Question 10

What is the main cause of antiviral drug resistance?

Answer 10

Inadequate drug levels

Question 11

How can antiviral drug resistance be prevented?

Answer 11

• Combination drug therapy
• Increasing adherence (e.g. therapies with lower pill burden)
• Sequencing to identify baseline drug resistance

Question 12

Describe two types of drug resistance assays.

Answer 12

• Genotypic assay - identify drug resistance mutations - used in HIV
• Phenotypic assay - grow the virus in monolayers in the presence of increasing concentrations of antiviral drugs (plaque reduction assay) - routinely used for HSV

Question 13

What are most cases of HSV drug resistance caused by?

Answer 13

Mutations in viral thymidine kinase

Question 14

What are most cases of CMV drug resistance caused by?

Answer 14

Mutations in UL97 protein kinase gene

Question 15

What are the main treatment options for drug resistant HSV and CMV infection?

Answer 15

Foscarnet and cidofovir

Question 16

How does oseltamivir resistance occur?

Answer 16

Neuraminidase mutation

Question 17

Name some pre- and post-exposure uses of antibodies?

Answer 17

Pre-exposure

• Palivizumab - RSV bronchiolitis

Post-exposure

• HBV Ig - neonate
• Rabies Ig - risky bite in unvaccinated
• VZIG - pregancy