HIV PT 1: Epidemiology, Transmission, Disease Course, Laboratory Tests

Question 1

Northern Alberta Program

Answer 1

• Northern Alberta Program ~ 2500
  patients
• 3 sites: KEC, RAH, STI clinic
• Interdisciplinary Team: ID
  physicians, pharmacists, nurses,
  social workers, dietitian,
  psychologist, psychiatrist,
  neurologist
• Antiretrovirals:
  – High drug cost program
  – Available at Rexall KEC and RAH
• Partnerships with pharmacies,
  community agencies, other
  programs (e.g. ACE team)

Question 2

Human Immunodeficiency Virus
Infection

Answer 2

• acquired immunodeficiency
  syndrome (AIDS) first
  recognized in 1981
• human immunodeficiency
  virus type 1 (HIV-1) - major
  cause of AIDS
• HIV-2 also recognized to
  cause AIDS but is much less
  prevalent

Question 3

Global HIV Statistics

____ of people living with HIV were accessing
antiretroviral therapy
____of people living with HIV knew their status

Answer 3

~38 million people were living with HIV at the end of
2021
– more than 2/3 living in Sub-Saharan Africa
(poverty and HIV denialism contributors)
* 75% of people living with HIV were accessing
antiretroviral therapy
* 1.5 million people became newly infected in 2021
* 85% of people living with HIV knew their status

Question 4

Targets for Ending the HIV/AIDS
Epidemic

HIV Testing and Treatment Cascade
Global -2019

Answer 4

ok

Question 5

Epidemiology in Canada
Key populations disproportionately affected
how many not aware of status

Answer 5

~62,790 people living with HIV in Canada in 2020
* 1 in 8 are not aware of their status
* 1722 new HIV diagnoses in 2021
* Key populations disproportionately affected
– Indigenous peoples
– Gay and bisexual men
– People who use drugs
– People with experience in the prison system
– People from countries where HIV is endemic

Question 6

Importance of community in policies,
testing and treatment of HIV

Answer 6

• Policy and programs aimed at supporting HIV prevention
  (and testing/treatment) need to address the needs of
  populations most impacted by HIV (e.g., Safer injection sites)
• Community-based organizations and individuals with lived
  experience play a critical role in advocacy but also in policy,
  programs and delivery of care (e.g., peer navigators, peer
  testing)
• Examples: Canadian Aboriginal AIDS Network, Canadian AIDS
  Society, HIV Edmonton, Canadian HIV/AIDS Legal Network,
  Alberta Community Council on HIV

Question 7

Transmission of HIV

Answer 7

sexual
parenteral
perinatal

parental as you can imagine
is, is anything from needle stick injuries to contaminated blood to sharing needles. or you know any other way that blood there’s blood contact that’s that’s has HIV

Perinatal transmission: 25% wihtout intervention, much higher than hep C
interestingly, it can also be transmitted through breastfeeding, which is, this is a bit unusual for some of these viruses

Question 8

Risk of Transmissible HIV

Answer 8

• Risk increases with higher HIV viral load
• STIs can increase risk of transmission
• U = U (undetectable = untransmissable)

substantial
low but nonzero
negligible or none

Stis can increase the risk of transmission of of HIV and some concurrent sti’s increase the risk even more
So some stis can cause more lesions and and sores which create a nice portal for entry.

if people are on treatment and their virus is controlled, it’s not possible to transmit sexually.

But what happens when you get a local infection? So whether it’s on your skin, or you know genital area, or what what happens in your body’s immune response. You get more inflammation and you get more information and you get cells that move to those sites to try to help out.

Question 9

Risk of Transmission by Exposure Type

Answer 9

• Highest risk
  with anal
  receptive
  intercourse
  and needle
  sharing

low risk oral
moderate: insertive anal, vaginal

Question 10

Perinatal Transmission

Answer 10

• Risk ~ 25% in the absence of treatment
• Risk increased with higher HIV viral load,
  duration of ruptured membranes, mode of
  delivery, breastfeeding

in countries that exclusively breastfeed or breastfeed for much longer than the average in in develop in in countries like Canada.
Some of the literature says it’s more like 30 t0 35% risk of transmission overall in the absence of treatment so again, highest risk with viral load.

if there was no interventions, the longer the re membranes are ruptured at the time of delivery. The type of delivery, as well as breastfeeding, can contribute

Vaginal delivery would increase the risk versus c-section in someone who’s not on treatment.
but fortunately with treatment vaginal delivery is safe and and actually preferred.

Question 11

Strategies for HIV Prevention

Answer 11

• Safer sex practices (e.g. condom use)
• Identifying and treating STIs
• Needle exchange programs, sterilized
  equipment, opiate agonist therapy
• Pre-exposure prophylaxis (PrEP)
• Post-exposure prophylaxis (PEP)
• Treating individuals living with HIV
  – includes pregnant individuals (perinatal)

Question 12

Benefits of Expanding Testing

Answer 12

. Why is it so important to drive down by remaining the community

it’s people that don’t know
that they have HIV. So again, they’re a smaller percentage of of the overall group but
account for about almost 40% of of new cases of HIV. So again just comes down to not being able to to reduce risk of transmission.

that has become a lot more
aware and and shown in studies and and leading to changes in how we we manage things.

Question 13

Clinical Progression of HIV

Answer 13

blue squares are your CD. 4, Your immune cells and the the Red Triangles are HIV Rna, or what we call viral load

when you first get exposed to HIV again you have, or acute HIV syndrome. Those flu like symptoms, weight loss, increased lymph glands
- what’s happening in this phase that you get really, really really high rates of of HIV replication.
- it just seeds all types of organs and and other parts of the body it’s referred to as the HIV Reservoir.

after that acute syndrome, what happens is is the viral load tends to to go down and reach what we call a set point.
and everybody’s set point is is different, and it really comes down to kind of how well everyone’s immune system can control the virus.

actually so there are some people who actually are living with HIV. They’re by far a very small percentage, but they’re called long term non predecessors, and some of them actually have an undetectable vir load without even treatment; or some have very, very low amounts of viral load

bottom line is is without intervention. On average kind of 8 years. People would then start to get more and more symptoms, opportunistic infections. Their immune system sort of loses control completely of the virus, and ultimately, on average, death would happen in about 10 years,

Question 14

Acute Retroviral Syndrome:
Signs and Symptoms

Answer 14

Most common symptoms:
– Fever
– Maculopapular rash
– Lymphadenopathy
– Myalgia or arthralgia
– Pharyngitis
– Oral ulcers
– Weight loss

Question 15

Definition of AIDS (CDC 1993)

Answer 15

• CD4 < 200 cells /μL (CD4 cell count not part of case
  definition in Canada)
• opportunistic infections (e.g. PJP, CMV, MAC,
  esophageal candidiasis, cryptococcus)
• HIV-associated encephalopathy
• HIV-associated wasting
• HIV-related neoplasms
  – Kaposi’s sarcoma, non-Hodgkin’s lymphoma

Question 16

Establishing HIV Infection

Answer 16

HIV initially replicates in MPs, CD4+ lymphocytes, andpossibly dendritic cells in tissue and blood
– normally dendritic cell presents a captured antigen to a CD4+ T cell → stimulates cell to activate and proliferate
– infected cells bring HIV particles to lymphoid tissues
* HIV infects activated T cells - dendritic and other APC’s promote additional rounds of HIV infection and replication
* Firmly establishes HIV infection in the lymphoid organs, where replication continues at a very high rate

it starts to replicate in those cells, like the antigen presenting cells and dendritic cells that that are in those tissues.
and what those dendrite cells, then do is, take that antigen the this to CD 4 cells. So it takes it back into the lymphoid tissues, and to seed the body, and HIV then just starts to to really start, to replicate and and continue to to seeds throughout the body.

there is again a so window of time before it gets into more the lymphoid organs that you can interrupt that transmission and prevent transmission from from establishing itself.
once it does get into those lymphoid organs, and it’s more disseminated. Then, at this point we don’t have a way of of.
you know, preventing long term infection.

Question 17

Testing for HIV

Answer 17

• Consideration and discussion of HIV testing should be a
  component of routine medical care
  – Based on body of good quality evidence demonstrating individual and
  public health benefits of normalizing HIV testing
• Offer HIV testing when screening for other STBBI
• Earlier diagnosis and treatment with combination antiretroviral
  therapy (cART) – decrease transmission to others as well as
  reduce morbidity and mortality due to HIV infection
• Expanding options for testing needed to reach the undiagnosed
• Re-testing and frequency:
  – Individuals at high risk of HIV should be screened annually

one thing we’ve learned with HIV it’s not just the opportunistic infections or the advanced stages of of HIV that cause problems, but that actually HIV itself and the resultant. If inflammation that happens when the virus is not under control, can lead t0 0ther comorbidities
- Eg. CV conditions
HIV is associated with higher risk of of cardiovascular disease

Question 18

Testing in Pregnancy

Answer 18

• Pregnant individual should be offered HIV testing at
  the first pre-natal visit (opt-out)
• Pregnant individuals who test negative but continue to be at risk of HIV acquisition (e.g. ongoing risk behaviour, HIV-positive partner)
  – could benefit from regular retesting and testing at point of delivery
• Pregnant individuals who arrive for delivery without a prenatal HIV test on record – offer rapid HIV testing

individuals that are pregnant should be offer testing at their first prenatal visit. So that’s because that’s called opt out testing. So we’ve been doing this in Alberta since 1998

it’s been critical in reducing risk of transmission during pregnancy, b

individuals that are negative, but still higher higher risk of acquisition. The guidelines suggest a regular re testing, and certainly testing at the point of delivery, because the risk of transmission is the highest in and around delivery.
if someone did not get tested, it’s recommended to do a rapid test,

95 t0 96% of of women end up opting to be tested, and and very few opt out

Question 19

Standard HIV testing

Answer 19

• Performed by public health laboratories (e.g. Provincial Lab)
  – “Gold standard”
• Uses venous blood sample – requires blood draw
• 2-step process in the lab:
  – Step 1: Antibody/antigen screening (4th generation tests)
  – Step 2: Confirmatory testing of reactive results to step 1
  – *Results are not reported until Step 2 is complete for positive
  test results “True positives”
• Results typically take a week to return
• Available through family physician, STI clinic, ER, hospitals

Question 20

Point-of-care HIV testing (POCT) –
Rapid HIV test

Answer 20

• Only Health Canada approved test (to date): INSTI® HIV1/HIV-2 antibody test
  – Results available in 1 minute
  – Uses fingerstick blood sample – very easy to use
  – Equivalent to 3rd generation standard tests used by PHL (>99%
  sensitivity & specificity)
• Considered an HIV “screening test”
  – A reactive test result requires a standard test to confirm HIV
  diagnosis
  – False positive results are uncommon, but are more likely in a setting
  with a low prevalence of HIV (ie. low risk people/areas)
  – A negative result can be considered a true negative, unless the person
  is in the window period of infectivity

if you’ve been exposed in the last
2 t0 3 months, it has very high sensitivity and specificity of of picking it up last 2 t0 3 months or longer, so it doesn’t detect it if you were just exposed to the last couple of weeks.
However, it is just a screening test. So you still need to get a blood test to to confirm the diagnosis

Question 21

Provides patient information to
make informed decision to test for
HIV by POC

Answer 21

• What is HIV and how it is transmitted
  (allows assessment of personal risk)
• Benefits of knowing one’s status
• Discuss HIV test method and
  meaning of reactive/non-reactive
  result (including window period)
• Explore patient response if result is
  reactive
• Next steps following preliminary
  screening result (e.g., confirmatory
  testing, results forwarded to public
  health, linkage to care)
• Obtain verbal consent

Question 22

Provides opportunity to discuss with
patient the implication of result and
next step of action:

Answer 22

Inform patient of result
- Non-reactive - discuss window
period, need for repeating testing,
risk reduction counselling, referral
services and supports
- Reactive – preliminary resultconfirmatory testing needed; focus
on positive messages; immediate
needs and social support; answer
questions and explore concerns; risk
reduction counselling

Question 23

HIV self-test in Canada

Answer 23

• Licensed in Canada Nov 2, 2020
  – Uses fingerstick blood sample – very easy to use
  – >99% sensitivity & specificity
• Considered an HIV “screening test”
  – reactive test result requires a standard test to confirm HIV diagnosis
• Can be purchased online (and in pharmacies) or distributed by
  community based organizations
• Challenges:
  – Delivery of pre- and post-test counselling & linkage to care (e.g., print inserts,
  telephone hotlines, websites, online videos, apps)
  – Support or counselling
• Canadian CIHR Centre for Reach 3.0
  – Working with community based organizations to launch tele-health program
  and distribute 60,000 kits
• Saskatchewan first province to announce free HIV self-test kits

Question 24

Dried Blood Spot Testing

Answer 24

• Can detect antibodies to HIV as well as HIV RNA
• Opportunities to expand availability of DBS (see
  advantages and disadvantages from HCV lecture)

Question 25

What lab tests are used to monitor HIV
infection?
Viral Load (HIV RNA)

Answer 25

• Measures amount of virus in the blood
  (copies/mL)
• Indications:
  – diagnosing acute HIV infection
  – surrogate marker for treatment response
  – assess risk of HIV transmission (e.g. perinatal,
  sexual etc)

The the main test we use is called a viral load, so it looks for the quant of quantifying HIV Rna.

it’s our main test. We use to to to see what treatment response is. So, again, what we call an undetectable or below the limited detection, which is less than 40 copies or not detected in in
Alberta’s assay is is the goal. but it also helps us assess risk of transmission.

Question 26

Viral Load (HIV RNA)
* Therapeutic monitoring:

Answer 26

– Goal: HIV RNA below limit of detection (VL <20-
50 copies/mL, depending on assay)
– Measured at baseline, and 4-8 weeks after
starting treatment; repeated every 3-4 months
* In very stable patients with suppressed viral load may
repeat every 6 months

Question 27

CD4+ T-Cell Count (reference range
360-1600 x 106/L)

Answer 27

• Major indicator of immunocompetence
• Strong predictor of disease progression and
  survival
• Ordered at baseline and typically every 3-6
  months initially
  – In stable patients with suppressed viral loads,
  yearly CD4 monitoring (or less frequently) is
  reasonable

We do CD. 4, maybe at the beginning. But if if someone has a high CD 4 and assess, especially once, your viral load is suppressed.
It’s not really necessary to monitor, because it’s not going to go down when someone is, is fully suppressed and taking t