HIV/AIDS Flashcards
When did HIV begin?
1981 - initially called GRID - gay related immune deficiency
Who are over 50% of new infections transmitted by?
People who are unaware of their HIV status
** why encouraging the public to know their HIV status is a critical public health initiative
What populations are most affected by HIV infections in Canada?
- Men who have sex with men
- Injection drug users
- Aboriginal people
**Aboriginal people overrepresented in Canada’s HIV epidemic = rate of new infections 2.7x higher than other groups
What is the largest population of people living with HIV?
Globally 38.4 million people living with HIV
Largest population is sub-Saharan Africa = 69% of all global HIV infections
Compare and contrast HIV-1 and HIV-2.
Similarities: both have similar structure and function
Differentiated by: envelope glycoproteins, point of origin, latency period
Where is HIV-1 found? Where was it believed to have originated?
Central Africa **origin
North America,
Europe,
Australia
What are the major classes of HIV-1?
M = main
N = new
O = outlier
+/- P = newest class
Where is HIV-2 found and what are the diseases general characteristics?
Found primarily in West Africa
1. milder disease
2. less virulent
3. longer latency period,
4. no clades
What are clades?
Distinctive branches or subtypes that HIV can be further divided into
- HIV has lots of clades due to the rapid rate of mutation
* individuals can be infected with more than one clade of HIV
How many clades are within HIV-1?
9 clades within the 3 main classes
What fluids can HIV be transmitted by? (5)
- Blood
- Semen
- Pre-ejaculate
- Vaginal secretions
- Breast milk
HIV transmission is a result of what?
Exposure to body fluids of infected individuals
Nature of exposure = risk of infection
What are the 3 main modes of HIV transmission?
- Sexual contact
- Blood contact
- Vertical/mother-to-child transmission (MTCT)
What are the 3 types of sexual contact that can result in HIV transmission?
- Anal sex - homo or heterosexual, higher risk of tearing/injury
- Vaginal sex
- Oral sex - oral lesions & contact with infections semen/secretions
What age group is more vulnerable to contacting HIV through vaginal sex and why? (3)
Young women, 13-25 yr are more vulnerable due to:
1. immature genital tract mucosa = less reliable mucous production = higher risk of injury
2. More likely to practice unsafe sex
3. Less likely to seek out or access healthcare
What are 3 categories of transmission under blood contact? Give examples of each.
- Injections/needles - sharing needles, needle stick injuries, infected tattoo/skin piercing instruments
- Contact with broken skin - sports, occupational hazard, developing countries
- Transfusions or transplant of infected organs or tissues - higher incidence in developing countries
When can MTCT or vertical transmission occur?
Pregnancy
Delivery
Breastfeeding
What 6 factors influence vertical transmission of HIV?
- Stage of infection
- Breastfeeding pattern
- Oral lesions in baby or breast lesions in mother
- GI illness
- Antiretroviral therapy
- Invasive procedures
How does stage of infections influence risk of vertical transmission?
Higher viral load occurs early in infection = increased risk of transmission = if an infection occurs during of just before pregnancy
How does breastfeeding pattern influence vertical transmission of HIV?
Breastfeeding patterns: exclusive vs mixed
- Exclusive has decreased risk than mixed
- Risk of transmission increases with duration of breastfeeding
How do oral or breast lesions influence vertical transmission of HIV?
Oral lesions in baby or breast lesions in mother = increase risk due to:
- increased portals of entry
- increased exposure to blood
How does GI illness in baby influence vertical transmission of HIV?
GI illness = weakened gut = increased portals of entry for virus in breastmilk
How does antiretroviral therapy (ART) influence vertical transmission of HIV?
ART significantly decreases risk during of transmission during pregnancy & labour/delivery
How do invasive procedures influence vertical transmission of HIV?
Ex. of invasive procedure = use of forceps during delivery
– can cause increased portals of entry and increase blood exposure
What virus family does HIV belong to?
Retrovirus family: viruses that carry their genetic material in the form of RNA and use the reverse transcriptase enzyme to convert RNA into viral DNA
What genus does HIV belong to?
Lentivirus genus: viruses (within the retrovirus family) that
- affect the nervous and immune systems
- have long latency periods
- have persistent viremia
- have more complex genome structure than other retroviruses
Describe the main elements of HIV’s structure.
- Envelope - gp120 spikes with gp41 stems
- Core - bullet shaped, surrounded by the capsid
- Within the core
- 2 identical strands of RNA
- 3 critical enzymes: reverse transcriptase, integrase, protease
Where can HIV be found at any given time? (5)
- Mucous membranes - macrophages & dendritic cells
- Actively infected CD4 lymphocytes
- Latently infected CD4 lymphocytes (can be latent for 2 years)
- Memory CD4 cells
- Floating or “free” virus
What are the ‘sanctuary sites’ of HIV? (2)
- Brain & CNS
- Immune system
What are the vulnerable target cells for HIV?
Uninfected but activated CD4 cells - they become infected when they arrive at the site of injury
Describe HIV’s summary of infection and what the result of that is.
- Portal of entry
- Virus taken up by macrophages +/- T-helper cells
- Virus replicates
- Either become latent or is released
- If released (cytolysis of infected cell facilitates virus release)
- increased viral load in blood,
- loss of B cell function
- immunodeficiency – opportunistic infections
What are the target cells for HIV?
** any cell that has CD4 receptors – T-helper cells, dendritic cells, microglia
Explain the receptors and co-receptors that are required for HIV to bind to host cells.
gp120 protein spike binds to CD4 receptors
co-receptors are required for different cell types:
- CCR5: co-receptors for binding to macrophages (are m-trophic)
- CXCR4: co-receptors for binding to T-helper cells (are t-trophic)
When do certain cell types become infected?
Macrophages become infected during early stages of infection
T-helper cells become infected during later stages of infection
What are the three phases of the HIV course of infection?
- Acute primary HIV infection phase
- Chronic asymptomatic or latency phase
- AIDS phase
How long is the progression of infection in an untreated person?
8-12 years
Define the acute primary HIV infection phase.
–> the time from initial infection to development of a detectable antibody response
usually 6-8 weeks
What lab results occur early in the acute infection phase?
In first 2 weeks:
- large amount of viral replication = increased viral load
- decreased CD4 count
What is peak viremia?
The mild flu-like symptoms (most experience rash to trunk) that occur 10-25 days after exposure and last 1-2 weeks
What is seroconversion?
The point in the acute phase where the immune system starts controlling viral replication = antibodies are present
– occurs 3 weeks to 3 months after infection (depending on health of person)
What is the window period or lag time?
The time between exposure and seroconversion where the person is infection but doesn’t have antibodies yet
- would give a false negative test
What is the viral set point?
The amount of virus that’s present after initial viremia and seroconversion (immune control) after
What important information does the acute phase tell providers?
The events of the primary infection = duration & intensity of symptoms –> important indicators of the individual’s disease course
Describe the chronic asymptomatic or latency phase of infection.
Where individual has stable viral load and doesn’t have signs or symptoms
What does ‘stable viral load’ mean?
When the number of newly infected cells equals the number of cells that die from infection
What happens to the CD4 count during the chronic asymptomatic phase?
CD4 count drops by 50-90 cells/microL per year = this accelerates over time
What is the median time for the latency phase?
In an untreated person = 10 years
What does the AIDS phase typically present with? (3)
- Opportunistic infections
- Secondary neoplasms/cancer
- Wasting syndrome
What are examples of opportunist infections that can occur during the AIDS phase?
- Karposi’s sarcoma
- lymphoma
- varicella
- bacterial & pneumocystis pneumonia
- TB
- toxoplasmosis
- cytomegalovirus (frequently occurs at end of life for AIDS patients)
Define wasting syndrome.
Unintended weight loss of >10% body weight – resulting in weakness, diarrhea, nutritional deficiencies
What is the CD4 count of a person in the AIDS phase?
< 200 cells/microL
What diagnostic information does the CDC use for staging HIV infections?
- CD4 count
- symptoms (more in developing countries)
What is a normal CD4 count?
1000-1200 cells/microL
What are the 3 stages and their CD4 counts that the CDC uses?
Stage 1: no significant immunocompromise = CD4 > 500
Stage 2: advanced immunocompromise = CD4 200-499
Stage 3: severe immunocompromise (AIDS) = CD4 < 200
Why is CD4 count useful in HIV staging?
** determining degree of immunocompromise
- can be used to reinforce clinical decision-making
- long-term prognosis is related to lowest measured CD4 count
What is important to note about CDC stages?
They can be downgraded but not upgraded – aka you can get worse but not better
What factors influence the time it takes for the immune system to create HIV antibodies? (4)
- genetics
- how transmission occurred
- the amount of virus person was exposed to
- if post-exposure prophylaxis occurred
What are 3 methods of screening for HIV?
- Point of care (POC)/rapid HIV testing = looks for antibody presence (seroconversion)
- 3rd generation EIA (enzyme immunoassay)
- Home test kit
What confirmatory tests are used for HIV?
Is a 2-step process
Step 1: 4th generation EIA - if positive = proceed to next step
Step 2: western blot - gold standard
What test is used for acute HIV infection testing? Who is it used for?
P24 antigen test to diagnose acute infection - detects viral RNA in plasma
- used for high-risk exposures, high risk populations, infants
When can the p24 antigen test be used?
As early as 2-3 days after symptoms start
Peaks at 3-4 weeks after exposure
What is the P24 antigen test called in BC?
RNA NAAT
What are 4 important lab values that are monitored
- CD4 count
- CD8 count
- CD4/CD8 ratio
- Viral load
What happens to CD4 count 6 months after seroconversion?
CD4 count drops by ~30%
What happens to CD8 count 6 months after seroconversion?
CD8 count rises by ~40%
What is the normal CD4/CD8 ratio?
Person without HIV, ratio > 1 = usually 4:1
What is the CD4/CD8 ratio in HIV positive individual? What is the result?
ratio < 1 – usually 0:08
Result – less CD4 cells to activate CD8 cells = less able to activate cell-mediated immunity = it’s less effective
What is viral load reported as?
** the actual amount of free virus in the plasma
Reported as # of virus copies detected in 1ml
What are 3 tests that can measure viral load?
- HIV RNA amplification (RT-PCR) test
- Branched chain DNA (bDNA) test
- Nucleic acid sequence based amplification assay (NASBA)
How is baseline viral load measured?
2 measurements 2-4 weeks apart after positive serology test
- continue monitoring every 3-4 months
What is baseline viral load used to determine?
- when to start antiretroviral therapy
- making adjustments to ART
What does viral load tell us?
- relationship between the virus & rate of disease progression
- rate of viral turnover
- relationship between immune system activation & viral replication
What happens to CD4 and CD8 counts as viral load increases?
CD4 decreases
CD8 increases
What are the 5 categories of antiretroviral drugs?
- Fusion inhibitors
- Protease inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
- Co-receptor inhibitors
How do fusion inhibitors work?
Inhibits ability of virus to fuse with host cells by binding to gp41 - becomes rigid & can’t make configurational change
** enfuviritide (fuzeon) or T20
How to protease inhibitors work?
Blocks protease enzyme which blocks viral assembly
** atazanavir (Reyataz)
side effects: lipodystrophy & hyperglycemia
What are the two types of reverse transcriptase inhibitors?
- Nucleoside reverse transcriptase inhibitors (NRTIs) = nukes
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) - non-nukes
How do nucleoside reverse transcriptase inhibitors work?
Blocks reverse transcriptase = premature termination of DNA strand
Side effects: lactic acidosis, hepatomegaly
** AZT or ABC
How do non-nucleoside reverse transcriptase inhibitors work?
Bind to reverse transcriptase = prevents conversion of RNA to DNA
side effects: rash
** delaviridne (rescriptor)
How to intgrase inhibitors work?
Stops transfer of viral RNA into host DNA
** kaltegravir (isentress)
How do co-receptor inhibitors work?
CCR5 Antagonist - blocks co-receptor to prevent fusion of virus to host cell
** maraviroc (celsentri)
What are the treatment recommendation and clinical stages from the BC centre for excellence in HIV/AIDS?
- if symptomatic or have CD4 < 500 = start treatment
- if asymptomatic with CD4 > 500 but have risk factors = start treatment
What 5 risk factors are considered by the BC Centre for Excellence in HIV/AIDS when starting treatment?
- Increased risk of disease progression
- Age > 50
- HIV-associated kidney disease
- Pregnancy
- Risk of HIV transmission
What is the first indication of success HIV treatment via antiretrovirals?
Decrease in viral load
How is the efficacy of HIV ART monitored?
Regular assessment of viral load and CD4 count
– checked at 4 weeks, then every 4-8 weeks until suppression is achieved, then every 3-4 months for the first year
How is the ART concentration in the blood monitored and what is it used for?
Peak & trough values
Used to:
- predict toxicity
- max efficiency
- evidence of adherence
What are some of the reasons why ART may fail to suppress viral replication? (5)
- Incomplete adherence
- Poor absorption
- Toxicity/side effects = pts lowering or missing doses
- Pharmacokinetic interactions
- Infected with resistant viruses
What are some of the long-term side effects of ART? (7)
- Kidney problems
- Liver problems
- Decreased bone density
- Skin rash
- Nerve problems
- Pancreatitis/diabetes
- Changes in fat metabolism
What information do we know about ‘curing’ HIV?
- Only 5 people globally have been cured
- Difficult to determined if ‘cured’ due to long latency period
- Cure was: person had blood cancer, underwent stem cell transplant from donor with CCR5 mutation
What is HIV resistance testing useful to determine?
- What drugs not to use in patients with increasing viral loads despite therapy
- Used in previously untreated individuals who may be infected with resistant HIV strain
** similar to C&S testing for bacteria
