Antivirals

Question 1

Which viruses does acyclovir treat?

Answer 1

HSV, VZV, EBV

Question 2

How does acyclovir work?

Answer 2

Activated by viral thymidine kinase. Once activated, can block viral DNA extension by competitively inhibiting viral DNA polymerases

Question 3

What is acyclovir an analogue for?

Answer 3

Guanosine

Question 4

Why is acyclovir not an effective treatment for CMV?

Answer 4

CMV lacks the thymidine kinase enzyme

Question 5

Which viruses does gangciclovir treat?

Answer 5

CMV, EBV, HHV-6

Question 6

What is a side effect of ganciclovir?

Answer 6

Bone marrow suppression

Question 7

Who requires treatment for CMV?

Answer 7

Neonates (congenital)
Immunocompromised
Pregnancy
HIV

Question 8

RCHEP is a mnemonic for the effects of CMV. What does it stand for?

Answer 8

Retinitis
Colitis
Hepatitis
Encephalitis
Pneumonitis

Question 9

What do cells infected with CMV show on microscopy?

Answer 9

Owl’s eye inclusions

Question 10

If resistant/allergic/sever side effects to ganciclovir, which 2 antivirals can be used instead?

Answer 10

Foscarnet

Cidofovir

Question 11

What is foscarnet an analogue of?

Answer 11

Pyrophosphonate

Question 12

How does foscarnet work?

Answer 12

Inhibits nucleic acid synthesis without requiring activation

Also used as prophylaxis post organ transplant

Question 13

What are the main uses of cidofovir?

Answer 13

Treating CMV retinitis (esp in HIV pts)

Treatment of non-herpes viral infections in opportunistic post-transplant setting (eg BK virus, adenovirus, JC virus)

Question 14

How does cidofovir work?

Answer 14

Inhibits viral replication by selectively inhibiting viral DNA polymerases

Also incorporates itself into viral DNA hence inhibiting viral DNA synthesis during reproduction

Question 15

Which organ do foscarnet and cidofovir cause toxicity to, and how is this side effect mitigated?

Answer 15

Nephrotoxic

Maintain hydration and co-administer probenecid

Question 16

The mnemonic for HSV (genital, oral, encephalitis, disseminated) treatment is Act Very Fast, what does this stand for?

Answer 16

Acyclovir
Valaciclovir
Famciclovir

Question 17

In a serious HSV infection what should be stared as early as possible?

Answer 17

IV acyclovir

Question 18

What is the treatment for a serious HSV infection + ganciclovir resistance?

Answer 18

Foscarnet/cidofovir

Question 19

In which pts does VZV require treatment?

Answer 19

Immunocompromised
Pregnant
Adults with pneumonitis

Question 20

What is the preemptive therapy for CMV in bone marrow transplants?

Answer 20

Monitor CMV viral load in the blood during high risk period

Question 21

What is the acute therapy for CMV in bone marrow transplants?

Answer 21

1st line: ganciclovir (but has marrow toxicity!)
2nd line: foscarnet (nephrotoxic) / ganciclovir+foscarnet combo
3rd line: cidofovir (nephrotoxic)

Question 22

What are the 3 criteria for deciding when to treat hep B (HBV)?

Answer 22

1) Serum HBV DNA levels (>2000IU/ml)
2) Serum aminotransferase (ALT, AST) levels (>normal upper limit)
3) Liver biopsy histological grade + stage: moderate-severe active necroinflammation and/or fibrosis

Question 23

What are the treatment goals when treating Hep B?

Answer 23

• Prevent progression to cirrhosis and hepatocellular carcinoma (HCC)
• Maintain serum HBV DNA level as low as possible
• Attain histology improvement
• ALT normalisation
• Loss of HBVeAg and seroconversion to HBVeAb

Question 24

One treatment option for HBV is pegylated interferon (INF) alpha 2a. How is this administered?

Answer 24

Subcut

Question 25

What are the 2 modes of action of pegylated interferon (INF) alpha 2a?

Answer 25

Direct antiviral effect

Upregulates expression of MHC on cell surfaces

Question 26

HBV can also be treated with nucleoside and nucleotide analogues. What are the 2 groups of these drugs?

Answer 26

Inhibitors of viral polymerase

Inhibitors of reverse transcriptase

Question 27

List 4 inhibitors of viral polymerase, used in the treatment of HBV

Answer 27

Lamivudine
Adefovir dipivoxil
Entecavir (no resistance)
Telbivudine

Question 28

Name an inhibitor of reverse transcriptase used in the treatment of HBV

Answer 28

Tenofovir

Question 29

What is the preferred 1st line treatment combination for HBV?

Answer 29

Entecavir
AND
PegINF alpha 2a
AND
Tenofovir

Question 30

What are the treatment goals when treating Hep C (HCV)?

Answer 30

• Sustained virologic response (SVR): persistant absence of HCV RNA in serum >6/12 after completing antiviral treatment
• Prevent progression to cirrhosis / HCC / decompensated liver disease requiring liver transplantation

Question 31

What is the treatment for HCV?

Answer 31

Combination of:

• PegINF alpha 2a/2b
• Ribavirin (RNA nucleoside analogue)

Question 32

What is the major side effect of ribivirin?

Answer 32

Haemolytic anaemia

Question 33

How many distinct genotypes of HCV are there and why is this clinically significant?

Answer 33

6 - genotype predicts response to treatment

Question 34

In which HCV genotypes is treatment more successful?

Answer 34

2 and 3 (~50% of UK burden)

Question 35

In which HCV genotypes is treatment less successful?

Answer 35

1, 4, 5 and 6 (~50% of UK burden)

Question 36

How are respiratory viruses diagnosed?

Answer 36

PCR-BAL
Throat swab
Nasopharyngeal aspirate (NPA)

Question 37

Which treatments are used for influenza and what is their route of administration?

Answer 37

Zanamivir (inhaled)
Oseltamivir (PO)
Amantadine (PO)

Question 38

What is the treatment for respiratory syncitial virus (RSV) /parainfluenza?

Answer 38

Ribavirin (guanosine analogue)