HIV and AIDS (lecture 1), Diseases- Yr 3,Wk 1

Question 1

How can HIV be spread?

Answer 1

• sexual transmission
• injection drug misuse
• blood products
• vertical transmission
• organ transplant

(think of high risk and unknown risk)
(High risk: multiple sexual contacts, men having sex with men and drug abusers)
(people who are not high risk are not low risk but instead they are unknown risk)

Question 2

HIV testing:

1) can an unconscious patient be tested for HIV?
2) Does having a negative HIV test affect your insurance premiums?

Answer 2

1) Unconscious patients can be tested if you think it is in the patient’s interest to have the test
2) Having had a negative HIV test does not affect insurance premiums

Question 3

Describe the Classification of HIV infection?

Answer 3

• Original classification was clinical
• Pragmatic approach is to consider symptomatic vs asymptomatic disease

(-CD4 cell count is a measure of your immune weakness/ immune damage
-HIV test is an ANTIBODY test so if recent exposure then may not have sufficient time to develop appropriate antibodies
Aids= ACQUIRED IMMUNODEFICIENCY SYNDROME
People can present with late stage HIV with AIDS related infection)

Question 4

What are the classification categories of HIV?

Answer 4

Clinical stage I-IV

Question 5

Describe clinical stages I-IV :

Answer 5

• Clinical stage I: Virus no symptoms
• Clinical stage II: mild symptoms (shingles)
• Clinical stage III: more marked symptoms (weight loss, diarrhoea)
• Clinical stage IV: more unusual condition- AIDs related conditions

Question 6

What are the top 3 questions asked at first doctors appointment?

Answer 6

• Do I have AIDs or HIV?
• How long have I had this infection?
• How long will I need to be on treatment?

Question 7

What are AIDs illnesses?

Answer 7

Certain infections and tumours that develop due to a weakness in the immune system are classified as AIDs illnesses

Question 8

When is it HIV infection ONLY?

Answer 8

If you have no symptoms then you have HIV infection only.

Question 9

Describe what usually happens to people with an AIDs illness?

Answer 9

virtually everyone with an AIDs illness should recover from it and then be put on antivirals to keep them free from any future illness
(HIV AND AIDS ARE IN EQUILLIBRIUM: ie 2 arrows pointing in opposite directions)
(present with AIDs and then treat it and put them on anti-virals and they should be asymptomatic
Or you can present with HIV and prevent it from progressing to AIDs with the use of anti-virals)

Question 10

What are the main type of cells of the immune system that HIV infects and destroys?

Answer 10

HIV infects and destroys cells of the immune system especially the T-Helper cells that are CD4+ (have a CD4 receptor on their surface)

Question 11

Are CD4 receptors exclusive to lymphocytes?

Answer 11

CD4 receptors are not exclusive to lymphocytes- they are also present on the surface of macrophages and monocytes, cells in the brain, skin, and probably many other sites

Question 12

What are the most important targets for HIV infection?

Answer 12

CD4 lymphocytes (T helper cells)- these are the most important targets for HIV

(CD4+ lymphocytes; needs this receptor to attach to the cell and thus it attaches and destroys the cell and thus there are not enough new ones produced in order to compensate for their destruction)

Question 13

Over the course of the infection; describe the cell count pattern:

Answer 13

over the course of the infection:
CD4 count declines and HIV viral load increases
-increasing risk of developing infections and tumours
-the severity of these illnesses is greater the lower the CD4 count
-Most AIDS diagnoses occur at CD4 count <200

(Different patients’ disease progress at different rates and a few have normal life expectancy with untreated HIV)

(The lower the CD4 cell count, the worse; don’t normally get symptoms until its less than 350)

Question 14

Describe the graph which shows HIV RNA load against CD4 against time

Answer 14

as time progresses, HIV RNA count increases and CD4 count declines and as time progresses, increasing likelihood of symptomatic HIV infection and opportunistic infections

(The greater the virus, the more damage to the CD4 cells)

Question 15

When are opportunistic pathogens (opportunistic infections) only capable of causing infection?

Answer 15

ONLY when the host defences are compromised

Question 16

What are the 2 types of infection that opportunistic infections can be?

Answer 16

-new infections (eg PCP, cryptospoidiosis)
or
-re-activation of existing infection (eg toxoplasmosis, CMV)

Question 17

Give an example of a reactivation of infection in HIV:

Answer 17

shingles

Question 18

List some HIV infection: opportunistic infections: NEW INFECTIONS:

Answer 18

• pneumocystis jiroveci (carinii) pneumonia
• candidiasis
• mycobacterium avium complex
• cryptosporidiosis

Question 19

List some HIV infection: opportunistic infections: reactivation infections:

Answer 19

• cerebral toxoplasmosis
• tuberculosis
• CMV disease

Question 20

In a patient who comes from Africa recently and has presented with TB….what do you want to do now?

Answer 20

HIV test

remember if CD4 count is high then they have better outcomes

Question 21

Give some AIDs defining conditions for the systems of:

a) respiratory
b) neurology
c) dermatology
d) Gastroenterology
e) oncology
f) gynaecology
g) opthalmology

Answer 21

a) Tuberculosis, pneumocystis
b) cerebral toxoplasmosis, primary cerebral lymphoma
c) Kaposi’s sarcoma
d) persistent cryptosporidiosis
e) Non-Hodgkin’s lymphoma
f) cervical cancer
g) cytomegalovirus retinitis

Question 22

Give some other conditions where HIV testing should be offered:

Answer 22

bacterial pneumonia, aspergillosis, aseptic meningitis/ encephalitis,
cerebral abscess, dementia, oral candidiasis

Question 23

Give the usual “natural history” of HIV infection:

Answer 23

acute infection- seroconversion –> asymptomatic –> HIV related illnesses –> AIDS defining illness –> death

(time from start to finish is extremely variable)

Question 24

Describe what happens when you have a declining CD4 population:

Answer 24

declining CD4 population- at risk of symptoms - introduce treatments -ART (anti-retroviral treatment) and you get the CD4 count higher and you lose the symptoms
-the later the diagnosis the worse the prognosis

Question 25

Describe Primary HIV/ seroconversion:

Answer 25

• Approx 30-60% of patients have a seroconversion illness (when HIV antibodies first develop)
• Abrupt onset 2-4 weeks post exposure, self limiting 1-2 weeks
• Symptoms generally non-specific and differential diagnosis includes a range of common conditions

(Primary HIV infection- when you get infected with a virus and your body recognises there is a virus. This is like a more severe form of glandular fever (high fever, high lymphocyte count- FAST onset)

Question 26

Give some symptoms which may occur in a primary HIV infection:

Answer 26

• flu-like illness
• fever
• malaise and lethargy
• pharyngitis
• lymphadenopathy
• toxic exanthema

(“looks like glandular fever but EBV serology not in keeping)

Question 27

If you suffered a seroconversion illness then….

Answer 27

…. then we can date the onset of the infection to that time

Question 28

If you had no seroconversion illness then…..

Answer 28

…..then the most accurate way of telling how long HIV has been present is to test stored samples of blood (if available)

Question 29

If no seroconversion illness or no stored blood samples then then…..

Answer 29

….then you should consider when you were at most risk

if you still don’t know, the stage of illness at presentation IS NOT helpful in estimating duration of infection

Question 30

In HIV infection, what are some ways of monitoring the disease?

Answer 30

• CD4 lymphocyte count
• HIV viral load
• Clinical features

Question 31

Name same antiviral drugs:

Answer 31

AZT, DDI, DDC, 3TC, D4T

There are a large number of antiviral drugs

Question 32

Describe the basis of antiretroviral therapy:

Answer 32

Different classes of drugs acting on different stages in the HIV lifecycle

Question 33

Describe combination antiretroviral therapy:

Answer 33

means at least 3 drugs from at least 2 groups

adherence needs to be over 90%- support patient

Question 34

Can cART lead to a normal life

Answer 34

cART can lead to a normal life but side effects can be significant eg metabolic, lipodystrophy

Question 35

Where to the treatments act?

Answer 35

1) Binding and entry: ENTRY INHIBITORS
2) Reverse transcription: REVERSE TRANSCRIPTION INHIBITORS
3) Integration: INTEGRASE INHIBITOR
4) Transcription
5) Assembly
6) Release and Protease: PROTEASE INHIBITORS

( RNA HIV virus attaches to CD4 receptor- virians get inside – the RNA transcribed to dna- the dna gets integrated into host cell dna by enzyme called integrase- the virus then matures and the protein maturation occurs and the protease inhibitors)

Question 36

When do you start and what do you start with?

Answer 36

When to start: When CD4 <350 cells/ mm3 or rapidly falling

What to start: Three drug combination with treatment adjustment if VL not adequately suppressed after 4-6 weeks of therapy

(As soon as your diagnosed, start treatment
Start treatment before they become symptomatic- to prevent AIDs related illness developing
Transmission in pregnancy around the time of delivery- if detected before this then it decreases the risk of transmission)
(vertical transmission
VL= viral load- measured after 4 weeks- to make sure that its undetectable in the blood)

Question 37

Improving Outcomes with evolving antiretroviral regimens:

Answer 37

This is what can be achieved with monotherapy and specifically with nucleoside analogues since those were the first drugs available. One can see a modest rise in CD4+ cell counts of approximately 50 cells/mm3 and a relatively modest decline of 1.0 to 1.5 log10 copies/mL in viral load. However, if a patient stays on monotherapy, over time one sees a decline back toward baseline in CD4+ cell count and a rise toward baseline in viral load.

If one samples the viral population in a patient who has shown this kind of response, one will find that the predominant virus is resistant to the drug the patient is on. This was demonstrated primarily with zidovudine because that was the first drug used as monotherapy, but subsequently, with other drugs given as monotherapy, we saw exactly the same effect. With monotherapy with nucleoside analogues, one would typically see a response of around 18 months, meaning that at approximately 18 months after starting therapy with a nucleoside analogue, one would see the CD4+ cell count and viral load return to baseline.

Question 38

What is the current life expectancy?

Answer 38

Life expectancy according to CD4 Nadir (lowest CD4 before starting therapy) in patient diagnosed aged 20:

<100: 52
100-200: 62
>200: 70+

Question 39

Why is AIDs diagnosis going down?

Answer 39

Due to antivirals

Question 40

How long will the patient need to be on treatment for?

Answer 40

• Once you start treatment you need to continue it for the rest of your life. The treatment may need to be changed from time to time but you will always need to be taking some form of antiviral medication.
• In many ways, the treatment of HIV is similar to that of a chronic condition (like hypertension) rather than to the treatment of an infection.

Question 41

Why do treatments fail?

Answer 41

Due to poor adherence which leads to viral mutation and resistance

(resistance usually due to poor drug compliance with medication- not taken regularly enough)

Question 42

List some antiviral drugs and their side effects:

Answer 42

-Nucleoside reverse transcriptase inhibitors:
marrow toxicity, neuropathy, lipodystrophy

-Non-nucleoside reverse transcriptase inhibitors:
skin rashes, hypersensitivity, drug interactions

-Protease inhibitors:
drug interactions, diarrhoea, lipodystrophy and hyperlipidaemia.

-Integrase inhibitors:
rashes

(Side effects of the drugs is not extremely important as the drugs are getting more and more cleaner)

Question 43

What should happen in someone with lipodystrophy (change in where fat develops: centrally and lose fats from the legs, more to the face):

Answer 43

• Change drugs: Less likely to occur with newer agents
• Cosmetic procedures: facelift, liposuction, fillers

(side effect of anti-virals: redistribution of body fat- redistribute the fat centrally)

Question 44

Describe Cardiovascular disease and HIV:

Answer 44

• Hyperlipidaemias
• Insulin resistance
• Direct drug effect
• Increased incidence of MI through unknown mechanism in patients with HIV

Question 45

List some challenges associated with HIV care:

Answer 45

• osteoporosis
• cognitive impairment
• malignancy
• DM
• IHD
• Renal disease
• Cerebrovascular disease

(challenges is about an ageing population: patients are more likely to get some of these side effects)

Question 46

List some ways in which HIV prevention can take place:

Answer 46

-Behaviour change and condoms
-Circumcision
-Treatment as prevention
(VL undetectable = transmission risk of 1 in 100,000)
-Pre-exposure prophylaxis (PrEP)
-Post-exposure prophylaxis for sexual exposure (PEPSE)

(Circumcision reduces the risk of infection)

Question 47

Give an example of a study which took place in South America:

Answer 47

Iprex study

Question 48

What is PEP ‘TALK’?

Answer 48

PEP is a 4-WEEK course of pills you can take if you have been at serious risk of getting HIV

• PEP may stop HIV after it has entered your body
• The course must be started ASAP and no later than 72 hours after exposure to the virus