Week 2 - F - HIV life cycle, treatment, and reduced transmission

Question 1

HIV is spread only in certain body fluids from a person infected with HIV. These fluids are blood, semen, pre-seminal fluids, rectal fluids, vaginal fluids, and breast milk.

If a patient presents with Cd4+ count less than 200, what drug should be given as prophylaxis? (what does it help prevent) What is given if the patient also has rectal chlamydia?

Answer 1

If the CD4 count is less than 200 - give low dose co-trimoxazole as pneumocytic pnemonia prophylaxis

(also helps to prevent toxoplasmosis (appears at <150cells/mm3))

• If the patient has rectal chlamyida - treat with doxycycline

Question 2

What cell types have the CD4 receptor for the HIV virus to bind to?

Answer 2

Mainly the T helper lymphocytes

But also dendritic cells, macrophages and microglia

Question 3

As well as the CD4+ receptor, the HIV virus binds to one coreceptor Name one of the two coreceptors that the HIV virus binds to as well as the CD4+ receptor to enter the cell? How often does the HIV virus replicate?

Answer 3

The coreceptors that it binds to are either CCR5 or CXCR4 - these are different chemokine receptors

HIV virus replicates every 6-12 hours in the early stages of infection

Question 4

In the HIV cycle, the free virus binds to the CD4+ receptor and then the virus fuses with the cell wall and enters the cell

Once the virus enters the cell, what happens up until transcription?

Answer 4

The reverse transcriptase enzyme from the virus produces own viral DNA from its RNA genome

The integrase enzyme then (from the virus) then integrates the virus into the cell’s own DNA

It is at this stage when transcription occurs

Question 5

What happens at transcription of the virus after it is integrated into the cells own DNA? What is the other enzyme that helps turn the immature virus into a mature new working virus?

Answer 5

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Question 6

If you’re diagnosed with HIV, you’ll have regular blood tests to monitor the progress of the HIV infection before starting treatment. Two important blood tests are what?

Answer 6

HIV viral load test - monitors the viral load in your blood

CD4+ lymphocyte cell count - monitors how the HIV is affecting immune system (<200cells/mm3 means chances of opportunistic infection greatly increased)

Question 7

Mono and dual therapy were tried as therapy for the HIV virus but the virus was very good to developing resistance to the treatment What are the three enzymes that are targeted for during treatment of HIV?

Answer 7

Target the reverse transcriptase, integrase and protease enzymes

Question 8

What is the current HIV treatment? What is special about the drugs for this treatment?

Answer 8

High active anti-retroviral therapy (HAART)

A combination of three drugs from at least 2 different drug classes that the virus is suscepitble to

Question 9

What is the purpose of the HAART therapy for HIV? IS this a cure to HIV?

Answer 9

The purpoe is to lower the viral load and restore immunocompetence - this reduces mortality and morbidity

This inst a cure to HIV

People were given 2 drugs of one class and another drug of another class – therefore working at two different points in the virus cycle, the drugs began to work

CD4 cells should ccme up again, and viral load should be reduced to be undetectable

Question 10

What are the different type of drugs that are available for use in HAART treatment of HIV? (there are 4 main types)

Answer 10

• * Nuecleoside reverse transcriptase inhibitors (NRTI)
• * Protease inhibitors (PI)
• * Ingtegrase strand transfer inhibitors (InSTI)
• * Non-nucleoside reverse transcriptase inhibitors (NNRTI)

Question 11

What is the key to preventing drug resistance in HIV?

Answer 11

Adherence is the key to preventing drug resistance in HIV

Question 12

What are the aims of the anti-retovrial treatment of HIV? (to ensure compliance)

Answer 12

• Low toxicity
• Low pill burdern
• Low dosing frequency
• Minimal drug interactions
• High barrier to resistance

Hard for the virus to make three simultaneous mutations against the medication

Question 13

What is a normal CD4 count again?

Answer 13

Normal CD4+ lymphocyte count is 500-1600 cells/mm3

Question 14

What was the first anti-HIV drug to be discovered? What class of anti-retroviral was it?

Answer 14

This was zidovudine - it is a nucleoside reverse transcriptase inhibitor (NRTI)

Question 15

There are many different toxicities asscoaited with different HAART medications Which two anti-retoviral groups cause GI upset?

Answer 15

Protease inhibitors and integrase strand transfer inhibitors (InSTI)

Question 16

Which two drugs can cause Steven-Johnson syndrome?

Answer 16

Abacavir (NRTI) and nevirapine(NNRTI)

Question 17

Which ART group is a potent liver enzyme inducer? Which group is generally potent liver enzyme inhibitors?

Answer 17

NNRTI are generally potnet liver enzyme inducers

Protease inhibitors are generally potent liver enzyme inhibitors

Question 18

What does the protease effect on the cytochrome p450 system mean for the ceoncentration of other drugs?

Answer 18

Due its effect of inhibiting liver enzymes, this will increase the concentration of other drugs in the body

Question 19

TB, largely driven by HIV and the treatments have large drug interactions What makes treatment for HIV more diffculties nowadays due to the age affected?

Answer 19

The age at when people become affected by HIV is increasing meaning there is more drug interactions as more co-morbidities come with increased age groups

Question 20

HIV can affect the psychoscocial well being of a person How is this so?

Answer 20

HIV can cause people to feel shame, confusion, guilt, blame and it is important not to forget this aspect of the disease

Question 21

Is it mandatory to notify your partner that you have HIV?

Answer 21

It is not mandatory but it is advised that the patient tells their partner that they have HIV

Question 22

If the GP knows that the patient and also has a patient who is with the1st one and the 1st is diagnosed with GP What does the GP do?

Answer 22

The GP should advise the 1st patient to voluntary tell the partner but as the GP has a duty of care to both patients, the GP must tell the partner if the diagnosed patient does not

Question 23

How is the onwards transmission of HIV prevented (for sexual intercourse)? What is a sero-adaptive sexual behaviour?

Answer 23

• Condnom use
• HIV treatment
• STI screening and treatment
• Sero-adaptive sexual behaviours - this is where patients seek out other HIV carriers to have sex with
• Disclosure
• Pre and post exposure prophylaxis

Question 24

What is done for pre and post expsorure prophylaxis? (PReP and PEP)

Answer 24

PReP - pre-exposure prophylaxis - if you are someone HIV negative sleeping with someone positive – can take medication to make likelihood of HIV very unlikely

Post exposure prophylaxis - must be started within 72 hours as HIV virus wont have infected CD4+ cells and is continued for at least 28 days

Question 25

HIV+ male, HIV- female WHat treatment is given here?

Answer 25

Treatment for the HIV + male (HAART)

And pre-exposure prophylaxis for the HIV negative female

Question 26

What is the likelihood of transmission of HIV in a patient with an undetectable viral load?

Answer 26

Likelyihood of transmission in a patient with an undetectable viral load is basically unheard of

Question 27

What is the prevention of mother to infant transmission of HIV? (ie if the mother is detectable or undetectable viral load)

Answer 27

• HAART treatment druing pregnancy
• Vaginal birth if undetectable viral load
• Caesarean section if detectable viral load and 4 weeks of PEP (postexposure prophylaxis) for neonate
• Exclusive formula feeding

Question 28

How is HIV transmission reduced? Via the sexual intercourse route How is Mother to child transmission (MTCT) reduced?

Answer 28

Sexual intercourse

• Condoms, disclosure, HIV treatment, STI screening and treatment, sero-adaptive sexual behaviours, Pre&post exposure prophylaxis

MTCT

• * HAART during prgenancy
• * Vaginal delivery if undectable viral load
• * Caearaen if detectable&4 weeks of PEP for neonate
• * Exclusive formula feeding for neonate

Question 29

What are the four different types of HIV drug treatments again?

• Which are potent liver enzyme inducers?
• Which are potent liver enzyme inhibitors?
• What was the first HIV drug? WHat group was it from?
• Which two can cause steven-johnson syndrome?

Answer 29

• * Nucleoside reverse transcriptase inhibitors (NRTI)
• * Non-nuecleoside reverse transcriptase inhibitors
• * Protease inhibitors
• * Integrase strand transfer inhibitors *
• NNRTI - potent liver enzyme inducers
• * PI - potent liver enzyme inhibitors
• * FIrst HIV drug - Zidovudine - NRTI
• * Both abacavir (NRTI) & Nevirapine (NNRTI) cause steven johnson syndrome