Anti Viral Agents

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

Abacavir - guanosine
Emtricitabine - cytosine
Tenofovir - adenosine
Lamivudine - cytosine
Zidovudine - thymidine

Question 4

Which two NRTI should not be used together?

Answer 4

Emtricitabine and lamivudine as they are both cytosine analogues

Question 5

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

Answer 5

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 6

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

Answer 6

1. Emtricitabine
2. Tenofovir
3. Lamivudine

Question 7

What should be used for patients with hepatitis B/ HIV virus coinfection?

Answer 7

An ART regimen for patients with both HIV and HBV should include Tenofovir alafenamide or tenofovir disoproxil fumarate(TAF or TDF) plus lamivudine or emtricitabine(3TC or FTC))

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 2 examples of integrase inhibitors and what is their route of administration?

Answer 10

Dolutegravir
Elvitegravir
Oral

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

Darunavir
Atazanavir
Ritonavir

Question 13

What are ritonavir and cobicistat used for?

Answer 13

They are used as pharmacokinetic boosters

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 decreases the metabolism of protease inhibitors.

Question 15

Name at least 2 adverse effects associated with protease inhibitors.

Answer 15

GI disturbances: Nausea, vomiting, and diarrhea.
Hyperglycaemia
Hyperlipidaemia
Hepatic injury
Lipodystrophy

Question 16

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

Answer 16

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 17

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

Answer 17

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

Question 18

Who is pre-exposure prophylaxis used for?

Answer 18

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

Question 19

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

Answer 19

Tenofovir and emtricitabine

Question 20

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

Answer 20

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

Question 21

Name 1 examples of NNRTIs

Answer 21

1.Efavirenz

Question 22

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

Answer 22

He should initiate PEP within the first 72 hours.

Question 23

Is PEP and PrEP treatment regimen the same?

Answer 23

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

Question 24

How long must an individual take PEP following an exposure?

Answer 24

28 days

Question 25

Name 2 drugs that are 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 25

Acyclovir
Valacyclovir (pro drug of acyclovir) (has greater bioavailability) (can be dosed less frequently)

Question 26

What is the mechanism of action of acyclovir?

Answer 26

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 27

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

Answer 27

Ganciclovir
Valganciclovir (pro drug) (can be dosed less frequently)
Notes that they has inhibitory activity against all herpesvirus.

Question 28

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

Answer 28

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 29

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

Answer 29

Valacyclovir

Question 30

What is the mechanism of action of ganciclovir?

Answer 30

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.

Question 31

Why should food be taken with valganciclovir?

Answer 31

It increases the bioavailability of valganciclovir.

Question 32

What are some adverse effects of Ganciclovir?

Answer 32

GIT related
Potential mutagenicity and carcinogenesis if patents crush or chew the drugs and touch such crushed tablets

Question 33

What is 1 type of HIV drug with compliance issues?

Answer 33

Protease inhibitors –> high number of capsules that need to be taken (“pill burden”)

Question 34

Name 1 advantage of tenofovir alafenamide over tenofovir disproxil fumarate?

Answer 34

Tenofovir alafenamide has more favorable effects on renal and bone markers –> use tenofovir alafenamide in pts with kidney impairment