Anti-virals

Question 1

What does a HIV antiretroviral regimen generally comprise of?

Answer 1

2 nucleoside reverse transcriptase inhibitors and either a(n)
integrase strand transfer inhibitor OR
protease inhibitor OR
non-nucleoside reverse transcriptase inhibitor.

Question 2

Name 2 examples of long-term toxicities associated with HIV antiretroviral treatment

Answer 2

1. metabolic syndrome
2. lipodystrophy syndrome

Question 3

Name the nucleoside reverse transcriptase inhibitors (NRTIs) and state which riboside’s analogue they each are

Answer 3

1. Abacavir - guanosine
2. Emtricitabine - cytosine
3. Tenofovir - adenosine
4. Lamivudine - cytosine
5. Zidovudine - thymidine

Question 4

What is the mechanism of action of nucleoside reverse transcriptase inhibitors?

Answer 4

NRTIs are analogs of native ribosides.
Upon cell entry, they are phosphorylated to the corresponding triphosphate analog, which is preferentially incorporated into the viral DNA by reverse transcriptases. Because the 3′-OH group is not present, a 3′,5′-phosphodiester bond between an incoming nucleoside triphosphate and the growing DNA chain cannot be formed, and DNA chain elongation is terminated.

Question 5

Which 2 NRTIs should not be co-administered?

Answer 5

Emtricitabine and lamivudine as they are both cytosine analogues

Question 6

Which NRTIs can also be used in the management of Hepatitis B?

Answer 6

1. Emtricitabine
2. Tenofovir
3. Lamivudine
   (An ART regimen for patients with both HIV and HBV should include (TAF or TDF) plus (3TC or FTC))

Question 7

Name 2 advantages of tenofovir alafenamide over tenofovir disproxil fumarate?

Answer 7

Tenofovir alafenamide has more favorable effects on renal and bone markers

Question 8

Which NRTI can only be used in HLA-B*5701–negative individuals?

Answer 8

Abacavir

HLA-B5701 is a genetic variation that is linked to hypersensitivity to the antiretroviral (ARV) drug abacavir. A person who tests positive for HLA-B5701 should not use abacavir or any other abacavir-containing medicine.

Question 9

What is the mechanism of action of integrase inhibitors?

Answer 9

The inhibitor binds and inhibits the catalytic site of the HIV integrase, which terminates integration of HIV DNA into the host genome.

Question 10

Name 3 examples of integrase inhibitors

Answer 10

1. Dolutegravir
2. Elvitegravir
3. Raltegravir

Question 11

What is the mechanism of action of protease inhibitors?

Answer 11

Protease inhibitors bind to the site where protein cutting occurs, and prevent the viral enzyme protease from releasing the individual core proteins.

Question 12

Name 2 examples of protease inhibitors

Answer 12

1. Darunavir
2. Atazanavir
3. Ritonavir is a PK enhancer

Question 13

Name at least 3 adverse effects associated with protease inhibitors

Answer 13

1. GI disturbances: Nausea, vomiting, and diarrhea.
2. Hyperglycaemia
3. Hyperlipidaemia
4. Hepatic injury
5. Lipodystrophy

Question 14

What is the mechanism of action via which the pharmacokinetic enhancer such as ritonavir works?

Answer 14

Low doses of ritonavir used have no significant anti-protease activity, but sufficient CYP450- inhibitory activity that interferes with the metabolism of protease inhibitors.

Question 15

Drug-drug interactions is a common problem associated with which class of HIV anti-viral drugs?

Answer 15

Protease inhibitors
(Drug interactions are a common problem for all protease inhibitors as they are not only substrates but also potent inhibitors of CYP450 isoenzymes.)

Question 16

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTI)?

Answer 16

NNRTIs bind HIV reverse transcriptase at an allosteric hydrophobic site to induce a conformational change resulting in enzyme inhibition.

Question 17

How does the entry inhibitor enfurvitide work?

Answer 17

Enfuvirtide is a polypeptide that binds to HIV fusion protein gp41, preventing the conformational change, and interfering with HIV-1 entry by inhibiting the fusion of viral and cellular membranes.

Question 18

How is enfurvitide administered?

Answer 18

Subcutaneous injection

Question 19

What is the mechanism of action of maraviroc?

Answer 19

Maraviroc blocks the binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor

Question 20

How may HIV acquire resistance to maraviroc?

Answer 20

They may preferentially express CXCR4 co-receptor, which would then limit the ability of maraviroc to block HIV entry.

Question 21

Who is pre-exposure prophylaxis used for?

Answer 21

It is useful when people are at a high risk of getting infected with HIV. (e.g. sex workers)

Question 22

Name an anti-viral combination that is used as PrEP.

Answer 22

Tenofovir disoproxil fumarate and emtricitabine (Truvada®)

Question 23

How long after the last possible exposure to HIV should an individual taking PrEP continue the medication before he/she stops?

Answer 23

He/she should continue for at least 4 weeks after the last significant exposure.

Question 24

Name 2 examples of NNRTIs

Answer 24

1. Nevirapine
   2.Efavirenz

Question 25

How soon after an exposure to HIV should an individual initiate Post-Exposure Prophylaxis?

Answer 25

He should initiate PEP within the first 72 hours.

Question 26

Is PEP and PrEP treatment regimen the same?

Answer 26

No. PEP treatment is similar to the treatment used for an established HIV infection. It will use the recommended 3 anti retrovirals regimen.

Question 27

How long must an individual take PEP following an exposure?

Answer 27

28 days

Question 28

Name a drug that is used in the management of conditions related to Herpes simplex virus type 1 and 2 and varicella-zoster virus such as cold sores, oral and genital herpes, and chicken pox.

Answer 28

Acyclovir
Valacyclovir
(More effective against HSV than VZV)

Question 29

Can acyclovir and ganciclovir be used at full dose in patients with renal impairment?

Answer 29

No. Caution is advised as the drug is cleared by glomerular and tubular filtration. Hence it can accumulate in patients with renal dysfunction. Dose adjustment will be required.

Question 30

What is the mechanism of action of acyclovir?

Answer 30

Acyclovir is a nucleoside analogue that is phosphorylated by viral thymidine kinase to acyclovir monophosphate, and host cell enzymes to acyclovir triphosphate form. It
1. Competitively inhibits viral DNA polymerase
2. Incorporates into and terminates the growing viral DNA chain, and
3. Inactivates the viral DNA polymerase.

Question 31

Which anti-viral is commonly used as a prophylaxis in immunocompromised patients against cytomegaloviral infections?

Answer 31

Ganciclovir
Valganciclovir

Question 32

Which antiviral has a better oral bioavailability, acyclovir or valacyclovir?

Answer 32

Valacyclovir

Question 33

What is the mechanism of action of ganciclovir?

Answer 33

It is monophosphorylated intracellularly by viral thymidine kinase and viral phosphotransferase during HSV and CMV infections respectively before being phosphorylated to diphosphate and triphosphates by cellular enzymes.

The triphosphate is a competitive inhibitor of the native deoxyguanosine triphosphate for incorporation into DNA and preferentially inhibits viral rather than host cellular DNA polymerases. Incorporation into viral DNA causes termination of DNA chain elongation.