HIV

Question 1

Modes of HIV transmission

Answer 1

• sexual
• blood products
• vertical (mum to child)
• needles

Question 2

Progression of HIV infection

Answer 2

Question 3

How does HIV seroconversion present?

Answer 3

HIV seroconversion = the time taken in which HIV antibodies develop and become detectable

• usually 3-12 weeks from an initial infection
• often (60-80%), but not always accompanied by symptoms of glandular fever (fever, swollen lymph nodes, rash, muscle aches)

Question 4

Features of HIV infection

Answer 4

Features

• sore throat
• lymphadenopathy
• malaise, myalgia, arthralgia
• diarrhoea
• maculopapular rash
• mouth ulcers
• rarely meningoencephalitis

Question 5

When to test for HIV infection in an asymptomatic patient?

Answer 5

• testing for HIV in asymptomatic patients should be done at 4 weeks after possible exposure
• after an initial negative result when testing for HIV in an asymptomatic patient, offer a repeat test at 12 weeks

Question 6

What’s HIV antibody test

Answer 6

• HIV antibody test*
• most common and accurate test
• usually consists of both a screening ELISA (Enzyme Linked Immuno-Sorbent Assay) test and a confirmatory Western Blot Assay
• most people develop antibodies to HIV at 4-6 weeks but 99% do by 3 months

Question 7

What confirms the diagnosis of HIV?

Answer 7

HIV PCR and p24 antigen tests can confirm the diagnosis

Question 8

What’s p24 test used for?

Answer 8

• p24 antigen test*
• usually positive from about 1 week to 3 - 4 weeks after infection with HIV
• sometimes used as an additional screening test in blood banks

Question 9

What’s the therapeutic management of HIV and its principles?

Answer 9

Highly active anti-retroviral therapy (HAART)

• involves a combination of at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)
• This combination both decreases viral replication but also reduces the risk of viral resistance emerging

Question 10

When are the patients start on HAART?

Answer 10

As soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated

Question 11

(2) aims of HAART

Answer 11

• to slow down HIV replication -> help the immune system to recover and fight other infections more effectively
• to reduce number of viruses -> viral number is low

Question 12

Why are there few drugs used in combination in HAART?

Answer 12

• typical treatment regimen involves taking 2 - 3 of these medications at the same time

if only one taken ⇒ usually the virus would get resistant

if few drugs given ⇒ virus dies before it becomes resistant

Question 13

In general, what drugs used in HAART act on?

Answer 13

The types of ART act on different steps of viral entry into CD4+ cell/replication pathway

Question 14

(6) drug classes used in HAART - just name

Answer 14

1. Fusion inhibitors
2. CCR5 antagonists
3. Nucleoside reverse transcriptase inhibitor (NRTI)
4. Non-nucleoside reverse transcriptase inhibitor (NNRTI)
5. Integrase inhibitor
6. Protease inhibitor

Question 15

Mode of action of fusion inhibitors

Answer 15

Fusion inhibitors

Bind to GP120 protein on HIV virus → virus cannot enter CD4+ cell

Question 16

Mode of action of CCR5 antagonist

Answer 16

CCR5 antagonist

Binds to co-receptor on CD4+ cell → so HIV virus cannot enter the cell

Question 17

Mode of action of Nucleotide Reverse Transcriptase Inhibitor (NRTI)

Answer 17

Nucleoside reverse transcriptase inhibitor (NRTI)

• NRTI → viral RNA cannot be converted into DNA (that otherwise could attach to host’s DNA)
• reverse transcriptase enzyme usually attaches nucleosides together to form a strand → NRTI attaches itself to nucleosides and prevents other nucleosides to attach to each other

Question 18

Mode of action of non-reverse transcriptase nucleotide inhibitor

Answer 18

Non-nucleoside reverse transcriptase

(NNRTI)

NNRTI → reverse transcriptase enzyme is prevented directly from acting on RNA (enzyme action inhibitor)

Question 19

Mode of action of integrase inhibitor

Answer 19

Integrase inhibitor

Enzymes called viral integrase would attach viral DNA into host DNA

• Integrase inhibitor prevents viral integrase enzyme → so virus cannot attach itself to the host’s DNA (the main trigger for cellular apoptosis)

Question 20

Mode of action of protease inhibitor

Answer 20

Protease inhibitor

• RNA polymerase would transcribe DNA (host + viral) into mRNA to produce
• proteins in ribosomes and protease enzymes would allow new proteins to be created

Question 21

Two mnemonics to remember HIV drugs action

Answer 21

• ‘Navir tease a pro’: HIV drugs that end with -navir are protease inhibitors e.g. ritonavir
• ‘It’s grave/great you integrate’: HIV drugs that end with -gravir are integrase inhibitors e.g. raltegravir