Diseases of The Immune System - HIV/AIDS II

Question 1

Briefly highlight the mechanism of action of Protease Inhibitors (PIs).

Answer 1

Protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

Question 2

What are the general adverse effects of PIs?

Answer 2

1. Lipodystrophy (Crix belly)
2. Hyperlipidaemia
3. Diabetes mellitus type 2
4. Kidney stones
5. Elevations in LFTs

Question 3

Mention 5 Protease Inhibitors (PIs)

Answer 3

1. Saquinavir (SQV)
2. Indinavir (IDV)
3. Ritonavir (RTV)
4. Lopinavir (LPV)
5. Atazanavir (ATV)
6. Nelfinavir (NFV)

SIRLAN

Question 3

Most PIs are usually administered as Boosted PIs whereby low-dose ritonavir (/r) (100-200mg) is co-administered with other protease inhibitors to block intestinal and hepatic 3A metabolism hence making it a once daily regimen.

True or False?

Answer 3

True.

Question 3

Highlight 4 drug interactions of PIs

Answer 3

1. Statins: PIS Increase the amount of statins in the body, leading to an increase in statins
   side-effects, such as muscle pain and kidney damage.
   Simvastatins and Lovastatins are
   contraindicated in all PIs.
2. Herbal supplements such as St. John’s Wort
3. OTCs such as antacids and fluticasone.
4. Prescription drugs: anticoagulants, anticonvulsants, antidepressants, antidiabetics, antibiotics and anti-anxiety medications

Question 3

PIs are also used to treat Hepatitis C

True or False?

Answer 3

True.

Question 3

What is the mechanism of action of capsid inhibitors?

Answer 3

They block the HIV-1 virus protein shell known as the capsid.

Question 3

Name one capsid inhibitor.

Answer 3

Lenacapavir (Sunlenca)

Question 4

Post-attachment Inhibitors are also known as ____.

Answer 4

Monoclonal antibodies

Question 5

What is the mechanism of action of Post-attachment Inhibitors?

Answer 5

They block the body’s HIV-infected cells from spreading the virus to those that are uninfected.

Question 6

An example of Post-attachment Inhibitor/Monoclonal antibody is ____.

Answer 6

Ibalizumab-uiyk (Trogarzo)

Question 7

Highlight the WHO recommended first-line regimen for HIV treatment.

Answer 7

1. Dolutgravir (DTG) + NRTI backbone - preferred first-line for adults and adolescents, as well as infants and children with aproved DTG dosing
2. EFV 400mg + NRTI backbone - alternative first-line for adults and adolescents initiating ART
3. Raltegravir (RTG)-based regimen - alternative first-line for adolescents as well as infants and children for whom approved DTG dosing is not available
4. Raltegravir-based regimen - preferred first line regimen for neonates

Question 8

Highlight the WHO recommended second-line regimen for HIV treatment.

Answer 8

1. DTG + optimised NRTI backbone - preferred second-line for people living with HIV for whom non-DTG-based regimen is failing. For adults, adolescents and children with approved DTG dosing
2. Boosted PIs + optimized NRTI backbone - preferred second-line for people living with HIV in whom DTG based regimens are failing

Question 9

Mention 7 factors affecting ARV regimen selection.

Answer 9

i. Virologic efficacy
ii. Toxicity
iii. Pill burden
iv. Dosing frequency
v. Drug-Drug interaction potential
vi. Drug resistance testing results
vii. Comorbid conditions

Question 10

LPV/r (Lopinavir/ low-dose ritonavir) is the PI available as a fixed drug combination.

True or False

Answer 10

True

Question 11

What are the primary goals of antiretroviral therapy?

Answer 11

i. Maximal and durable suppression of viral load
ii. Restoration and preservation of immunologic function
iii. Improvement of quality of life
iv. Reduction of HIV-related morbidity and mortality.

Question 12

What are the counselling points on ART?

Answer 12

i. ARVs do not offer a cure. HIV may be suppressed but is not eradicated from the body
ii. Use of ARVs is associated with improved quality of life and long term survival
iii. ARVs need to be taken daily for life to prevent development of resistance and treatment
failure
iv. ARVs, like other medications, are associated with side effects
v. Better results are obtained with good adherence to the treatment regimen
vi. Some patients may fail to respond to treatment and may require changes in their
treatment regimen.
vii. If patient thinks other treatment or their religious/traditional beliefs alone can manage their condition, they must be counselled to access those options now than after they have commenced treatment because the drugs are ‘unforgiving’ if not taken as they should be