Human Immunodeficiency Virus (HIV)

Question 1

How can HIV be transmitted?

Answer 1

Sex without a condom
Passed from mother to baby
Sharing injecting equipment
Contaminated blood transfusions + organ transplants

Question 2

What is the Point of Care Testing (POCT)?
Diagnosis

Answer 2

HIV Ab test (4-8 after exposure)
Finger prick test or mouth swab
Result in 20-30mins
High accurate >6 weeks exposure
Less sensitive than 4th generation

Question 3

What is the Fourth Generation Assay?
Diagnosis

Answer 3

HIV Ab + P24 Ag test (protein produced 2-3 after infection)
Blood sample sent to lab
Result may take 7-21 days
Highly sensitive after 4 weeks

Question 4

What is viral load (VL)?
Markers

Answer 4

Number of copies of HIV RNA in 1ml of blood

Question 5

What is undetectable?

Answer 5

<50 of viral load

Question 6

What is another marker?

Answer 6

The number of CD4+ T cells in 1mm3 blood

Question 7

What happens in the primary infection experienced after contracting HIV?

Answer 7

Seroconversion illness = fever, weight loss, mouth sores, myalgia, headache, rash + nausea + vomiting

Question 8

What is clinical latency?

Answer 8

Declining CD4 count
Stable viral load
Asymptomatic

Question 9

What does a declining CD4 count increase risk of?

Answer 9

Increased risk of opportunistic infection + lymphomas

Question 10

What is AIDS?

Answer 10

Advanced Immuno-Deficiency Syndrome

Question 11

What are the drug targets?

Answer 11

Attachment
Reverse transcriptase
Integration
Budding, release + maturation

Question 12

What are the goals of treatment?

Answer 12

Extend life expectancy + QOL
Viral load undetectable within 4-6months <20 copies/ml
Preserve + restore CD4 cell count
Prevent transmission

Question 13

What is treatment dependent on?

Answer 13

Presentation with or without AIDs

Question 14

When should treatment only be started?

Answer 14

When the patient is ready

Question 15

What are the PROS of early treatment?

Answer 15

Increased immunological recovery
Reduced transmission
Reduced disease progression
Reassurance to patient

Question 16

What are the CONS of early treatment?

Answer 16

Poor preparedness = low adherence + drug resistance
Long term side effects
Cost

Question 17

What do you do with the presentation of AIDs?

Answer 17

Start treatment within 2 weeks of antimicrobials

Question 18

What is IRIS?

Answer 18

Immune Reconstitution Inflammatory Syndrome
= initiation of ART = immune system recovers rapidly = increased inflammatory activity + autoimmune syndromes
May be fatal

Question 19

What is post-exposure prophylaxis (PEP)?

Answer 19

Needle stick injury
28 days treatment initiated within 72hr after exposure
TenofovirDX/emtricitabine + raltegravir 2 months (2xNRTI + integrase inhibitor)

Question 20

What is pre-exposure prophylaxis (PrEP)?

Answer 20

Take daily or PRN by HIV negative individuals
To prevent transmission for higher risk individuals
TenofovirDX/emtricitabine (2xNRTI)

Question 21

What are the 5 main classes of ARVs?
Need to be targeting 2 sites

Answer 21

NRTIs
Protease inhibitors
Integrase inhibitors
NNRTIs
Entry inhibitors

Question 22

What are examples of NRTI backbones?

Answer 22

TenofovirDX/emtricitabine
DX = disoproxil
TenofovirAF/emtricitabine
AF = alafenamide

Question 23

What are examples of protease inhibitors?

Answer 23

Darunavir/ritonavir
Darunavir/cobicistat

Question 24

What are examples of NNRTIs?

Answer 24

Efavirenz
Rilpivirine
Doravirine

Question 25

Describe the NNRTI backbone

Answer 25

Use 2 NRTI drugs + 1 drug from another class

Question 26

What is the MoA of NRTIs?

Answer 26

Block addition of nucleosides to DNA chain during retrotranscription Structurally resemble nucleotides BUT act to terminate building of DNA chain

Question 27

What are the pros of TenofovirDX/emtricitabine?

Answer 27

Preferred 1st line Superior to abacavir/lamivudine

Question 28

What are the cons of TenofovirDX/emtricitabine?

Answer 28

Cautioned in stage3-5 CKD Long terms effects on bone density

Question 29

What are the pros of TenofovirAF/emtricitabine?

Answer 29

Preferred 1st line Equivalent efficacy to TenofovirDX/emtricitabine Benefit in patients with renal/bone disease

Question 30

What are the cons of TenofovirAF/emtricitabine?

Answer 30

Cost Lack of experience - 2016

Question 31

Describe the structure of Tenofovir

Answer 31

Salts TenofovirDX/AF BOTH prodrugs

Question 32

What are the differences between TenofovirDX/AF?

Answer 32

DX = activated in plasma AF = activated intracellularly AF = lowers plasma conc + fewer side effects

Question 33

Why Abacavir avoided?

Answer 33

8% people allergic = associated with potentially fatal hypersensitivity reactions

Question 34

What is the MoA of protease inhibitors?

Answer 34

Bind to catalytic site of HIV protease Prevents processing of viral enzymes + core proteins Incomplete + non-infectious virions released

Question 35

What is the MoA of integrase inhibitors?

Answer 35

Viral integrase incorporates the HIV genome into host cell genome Block access to integrase

Question 36

What is the MoA of NNRTIs?

Answer 36

Bind to reverse transcriptase + impair function Viral DNA formation terminated

Question 37

What are the major CONS of protease inhibitors?

Answer 37

Horrible side effects = peripheral neuropathy, headache, vomiting, diarrhoea, abdominal pain, rash

Question 38

When are protease inhibitors good?

Answer 38

Can be started when unknown resistance = need resistance tests first for other drugs

Question 39

So what is treatment guidelines?

Answer 39

NRTI backbone = TDF/emtricitabine OR TAF/emtricitabine Third agent = darunavir/r or darunavir/c

Question 40

What are the causes of treatment failure?

Answer 40

Resistance Poor adherence Drug-drug interactions

Question 41

Describe ARV injectables

Answer 41

New option of patients with psychological or physical specific needs Deep IM gluteal injection every 2 months Strict criteria

Question 42

What drugs can be used for ARV injections?

Answer 42

Cabotegravir or Rilpivirine

Question 43

What is the criteria to be give ARV injectables?

Answer 43

Adult Virally suppressed (6 months) No existing or previous failure Commitment to 8 weekly appointments BMI <30