Lecture - HIV Public Health (2hours)

Question 1

How epidemiology helps guide provision of care:

1. Health service providers need to know prevalence of diagnosed cases to plan care - what questions should they ask? (4)
2. With better survival, what is happening that is adding to the challenges of providing HIV care?
3. What is the pattern of diagnosis of AIDS over the years and newly reported cases of HIV?
4. What is the cost like for govt for people receiving ARTs?

Answer 1

1. HOW many people need care,
   - 3000

WHO needs care
-Males more than females (mostly MSM)

WHERE do they live
-Auckland

WHAT are future needs of people with HIV

2. Many people under care are now ageing
3. AIDS - going down and death from AIDS going down but HIV diagnosis increasing. So the number under care/prevalence for HIV in NZ over the past few years is going up. This means we have to plan for more health care for people with HIV
4. In 2015, was 32mil

Question 2

How epidemiology helps guide prevention:

1. What can you say about the diagnoses in NZ among MSM?
2. What about heterosexuals?
3. Where should we aim specific HIV control? (3 groups)
4. What’s some prevention advice for individuals?
5. What are some health promoting strategies at population levels?

Answer 2

1. Basically, MSM is the target group for prevention (so gay or bi men). Like, we’re in bottom third of high-income countries but still HIV diagnoses in MSM is going up
2. Very small numbers as compared to MSM. The overseas infected people dropped off because tighter immigration laws now
3. MSM, groups with high prevalence (and areas where sexual conteact) annnnnd injecting drug users (although low HIV prevalence in NZ). Also, sex workers, general heterogeneity pop and if you control STIs then you also control HIV
4. Avoid risky sexual behaviours, unprotected sex esp with strangers and don’t share needles. You can manage factors that increase HIV acquisition so avoid other STIs and get circumcised.
5. Involve the affected communities, infected people, create a supportive environment, have support committed leadership and aim to de-stigmatise the disease and groups affected

Question 3

Epidemiology helps guide HIV testing (who should be tested)

1. Why is early diagnosis important for individual and population?
2. Who should the HIV test be offered to?
3. What’s the consent like for HIV testing?
4. Where does majority of the HIV transmission come from?
5. Can you say statistically say probability of transmitting is 0?

Answer 3

1. Individual: have improved immune system recover if catch early (before CD4 gets low aka catch when it’s still high). For the population: treatment as prevention.
2. If you have certain signs or symptoms like immunosuppression (have a clinical possibility go HIV)
   - If you have an STI
   - If you’re at risk of HIV (like have unprotected sex, inject drugs)
   - All pregnant women
   - Blood donations and immigration
3. It is oral consent and done once in a life time at least (it’s just like any other blood test)
4. From people unaware of their infection
5. Very hard to statistically say you can’t transmit it buttttt it seems impossible to transmit when have undetectable viral load

Question 4

How is HIV detected? Using what?

Answer 4

Use an antigen like p24 (in nucleocapsid) or HIV genome

Question 5

What is the window period?

Answer 5

When neither the AB, RNA or P24 antigen are there (but you have been infected)

Question 6

ELISA test is used to detect anti-HIV AB in human serum - how?

Answer 6

1. Coat wells with p24 antigen
2. Add patent serum (which should include the ABs you have made against it)
3. Wash so all the unconjugated AB go away
4. Then have an AB for the human AB and that will have an enzyme attached to it
5. Again, wash
6. Then add substrate for that enzyme
7. Then the colour should change if you have HIV bc the enzyme will react. See, if you didn’t have HIV (aka didn’t have AB) then in the washing steps, you wouldn’t have left any enzyme that could react with substrate to change colour)

Question 7

What is a 3rd vs 4th generation assay and when are they used?

Answer 7

3rd generation assays used to be used but they detect the AB only. 4th detect both AB and p24 antigen present in serum (so the ELISA test but opposite). ABs get made after the antigen is detectable so using 4th means you can detect and diagnose HIV earlier

Question 8

What are rapid tests that can be used with detecting HIV?

Answer 8

These are point of care tests that have immediate result. If a skilled person uses them then you’ll get a similar result to the lab test although lab test is gold standard. There is obviously potential for technical error if you aren’t skilled (since they aren’t automated) and you could be colourblind and not be able to read the result. Also, can use oral fluid but that increases false positives

Question 9

You can also use real-time reverse transcription polymerase chain reaction to detect the viral genome RNA of HIV - what is this?

Answer 9

So yeah, use reverse transcriptase and make DNA and then PCR to amplify it. Then use the probes and see the colour change. With the detection of fluorescence, can see how many visions in blood (basis of measuring viral loads)

Question 10

What’s the flowchart for HIV testing?

Answer 10

1. Do the test for the antigen and AB in lab
2. If negative then well, you’re either all good or you just tested early on in window period so test again later on
3. If positive then do the AB differentiation immunoassay which will tell you what sort of HIV you have.
4. If you get -ve for the AB differentiation assay then either you are negative (so first one was done wrong) or the differentiation was just done wrong or you have antigen but no AB yet. So either you do the test after a while (once Ab come round) or you do real time PCR.

Question 11

Testing in special circumstances:

1. Screening of blood donations - what sort of sensitivity is required and what is tested?
2. Pregnancy - what sorta test?
3. Infants - test what?

Answer 11

1. High sensitivity and test RNA, plus the lab test
2. Low pre-test probability (aka low probability that you have the condition) and you need rapid test. Only the lab test done
3. Test RNA.

Question 12

Interpretations of HIV screening test:

1. What is sensitivity?
2. What is specificity?
3. When you ask yourself, “does a person with a positive test actually have HIV” - what term is it and what is it dependent on?

Answer 12

1. Proportion of people with the disease who test positive (true positives)
2. People w/o disease who test negative (true negatives)
3. Positive predictive values - across rows. It’s dependent on prevalence. The higher number of people there are with the disease, the more that will test positive and so the higher the PPV.

Question 13

History of treatment:

1. How was treatment back in the day?

Answer 13

1. With treatment - we’ve swung from treating evreyone from get-go to then treating only those who need it and now treating everyoneeeee. There weren’t many options and didnt know how to use them

So what they did: they used to treat everyone then CD4 count improved and viral load dropped off and within weeks, their viral load would come back up, CD4 would drop off and resistant mutaitons would increase (bc only used one medication at a time). What they’d do this when one medication failed, they’d go to the next one in line and then when that failed, they’d use the next one in line etc. This created tons of resistance

Question 14

What is HAART?

Answer 14

Where you use 3 different drugs to target at least 2 different spots in cell cycle of HIV

Question 15

Management of a patient with HIV:

1. What do you do in the assessment?
2. You need to prevent other infections and problems - how?
3. What about discussing prevention of onward transmission - what can they do?
4. In terms of support, what can they do?

Answer 15

1. WHen perosn comes in with HIV, assess whether sick or healthy etc. HIV IS a notifiable disease NOW and AIDs is also so need to notify. First check CD4 count and viral load and other things like lier function
2. Do things like put on medication if CD4 real low so don’t get opportunistic infections.
   - Screen for Hep A, B and C and other STIs and TB (bc HIV patient can’t control TB and they’re more infectious to others).
   - You should advise them to stop smoking and take other measures to maintain CV health
3. Have safe sex, screen for other STIs (other STIs promote transmission of HIV), discuss pregnancy, safely inject etc
4. Disclose

Question 16

What’s the law around disclosure?

Answer 16

If using condom, then not legally required to disclose HIV status to your partner

Legal requirement - if have unprotected sex then need to disclose

Question 17

When are you considered for ART? What is assessed? And what is done for good adherence?

Answer 17

1. ART considered when CD4 is below 500 or you’re symptomatic or you develop AIDS or you’re pregnant or you are at high risk of transmission (like always have unprotected sex)
2. Readiness is assessed
3. On-going support

Question 18

What’re the principles of ART?

• complete what?
• how many drugs and how many classes?
• use a minimum of how many drug and from how many classes?
• what’s the currnent regimens?

Answer 18

• Aim for complete virologic suppression
• Currently > 20 drugs from 5 classes
• Use minimum of 3 drugs from 2+ classes
• Current regimens
– once daily
– fewer pills
– No food restriction

Question 19

What are some complications like side effects etc?

Answer 19

1. Side effects:
   - short term can be nausea, vivid dreams
   - long term can be lipodystrophy
   - emerging can be CV risk (since now ppl living longer)
2. Long term adherence can be a challenge - resistance may develop and you’re more likely to get resistance if poorer adherence

Question 20

Now onto drugs!

Entry inhibitors:
1. What are the two and what do they do?

Reverse transcriptase inhibitors (RTIs):
2. What are the two and how do they work?

Integrase inhibitors:
3. How does it work?

Protease inhibitors:
4. How do they work?

Answer 20

1. CCR5 inhibitor (e.g. maraviroc) prevents the binding of gp120 to co-recepto. There are also fusion inhibitors (e.g. efuvirtide) - peptide analogue of fusion domain of gp41 inhibits fusion
2. Nucleoside analogues (NRTI) and non-nucleoside RT inhibitors (NNRTIs). The first one is where they look like normal nucleosides but they aren’t so it will be incorportated by reverse transcriptase in viral DNA copy but then wont get integrated by DNA pol in the host DNA so toxic to virus but not host cell. the NNRTI just bind to another site on RT and prevent it from functioning.
3. Prevent integration of HIV cDNA into host
   genome. Increasingly being considered bc stop from virus integrating in genome so reduce reservoir
4. So as we know, GAG and POL require cleavage by protease for virus assembly. So if you get a substrate analogue - it will bind to the active site and prevent the maturation step of these poly-proteins

Question 21

Go read the rest of the slides for drugs and mutations in McAllister

Answer 21

-

Question 22

What are ways you can prevent HIV?

Answer 22

Behavioural (eg condoms)
• Circumcision
– 58% reduction in risk of infection

• Antenatal screening and treatment
• Treatment as prevention

• Post-­‐exposure prophylaxis (PEP)
– Start within 72 hours of exposure, continue 4 weeks
-Like if get needle stick from HIV infected patient then start ART - extremely effective so start asap

• Pre-­‐exposure prophylaxis (PrEP)
– Daily pill to reduce risk of becoming infected
– 44-­‐62% protection against infection
-So this is for people undertaking risky sexual behaviour who are uninfected. They can take a pill beforehand and if they are good at taing pills then good at reducing infection. Only good if you’re good at taking it

• Microbiocides
– 23 microbiocide products in various stages of clinical development

• Vaccines

Question 23

Prevention of mother to child transmission - how?

Answer 23

Risk of transmission without intervention ~30%

• Diagnosis essential
– Antenatal screening

• Antiretroviral therapy
– Mother from 14 weeks gestation or at diagnosis
– Baby from birth for 6 weeks

• Consider C-­‐section if viral load not suppressed

• Avoid breast-­‐feeding
– Extra 10% risk of transmission

• Reduces transmission to <1%
• Follow-­‐up testing of baby