CPTP 3.9 - HIV Treatment

Question 1

How does HIV bind to T-cell receptors?

Answer 1

Via GP120 molecule (facilitates cell entry)

Question 2

Describe HIV virus?

Answer 2

Retroviral RNA
Enveloped
P24 Ag encapsulates the viral RNA (capsid for protection)

Question 3

Which three proteins are found within the P24 capsid?

Answer 3

Reverse transcriptase - converts viral RNA into DNA
Integrase - Inserts this viral DNA into the hosts own DNA
Protease - cleaves the large polyprotien structure synthesised into smaller active proteins

Question 4

Define ‘chemotherapeutic index’?

Answer 4

Maximum tolerable dose per kg of body weight/minimum dose per kg of body weight - that will cure a disease (the higher the C.I the better)

Question 5

Name four categories of HIV treatments?

Answer 5

Nucleocidal reverse transcriptase inhibitors
Non-nucleocidal reverse transcriptase inhibitors
Fusion inhibitors (CCR5 and T20)
Integrase inhibitors

Question 6

Name a nucleocidal reverse transcriptase inhibitor and describe its mechanism of action?

Answer 6

Tenofovir
Looks like a free nucleotide and is mistakenly placed within the growing chain of the new viral DNA (made from reverse transcriptase) - further growth stops
Cellular effects = inhibits mitochondria by inhibit DNA polymerase which is essential for mitochondrial replication

Question 7

Describe two ways in which HIV resistance may occur against nucleocidal reverse transcriptase inhibitors?

Answer 7

Single point mutations =

1. Tenofovir (nucleotide analogue) is recognised by a mutant reverse transcriptase and removed by a cleavage process known as pyrophosphorylysis (PPi)
2. Lack of binding of viral reverse transcriptase to the tenofovir analogue to add it in the first place

Question 8

Name a non-nucleocidal reverse transcriptase inhibitor and describe its mechanism of action?

Answer 8

Efavirenze
Binds directly to the viral reverse transcriptase - preventing its function to add new nucleotides to the growing viral DNA chain

Question 9

Which mutation can lead to pan-resistance to non-nucleocidal reverse transcriptase inhibitors?

Answer 9

Mutation K103

Question 10

Name a protease inhibitor and describe its mechanism of action?

Answer 10

Darunavir

Protease breaks up the polyprotein formed by the mRNA into smaller active proteins used to make new HIV viruses

Question 11

How would HIV drug resistance be identified?

Answer 11

Suspected when viral load increases OR lack of viral suppression

Question 12

How are non-nucleocidal reverse transcriptase inhibitors and protease inhibitors metabolised?

Answer 12

Efavirenze and darunavir are both metabolised by CYP450 enzymes inside the liver