HIV Intro Flashcards
Differentiate between HIV 1 and HIV 2
Common?
Progression?
Transmissibility?
Location?
Testing?
Common?
- HIV-1 more common
Progression?
- HIV-2 immunodeficiency progresses slower
Location
- HIV-2 is mostly in west Africa
Transmissibility?
- HIV-2 is less transmissible
Testing
- HIV-1 tests do not reliably detect or quantify HIV-2
Where are the majority of people living with HIV
Africa
How is the progress on HIV treatment in Canada
% Diagnosed with HIV
% On treatment
% on treatment suppressed
89% know their HIV status
85% positive for HIV initiate treatment
95% on treatment are virally suppressed
What type of virus HIV?
What does it attack
Retrovirus (RNA virus with DNA intermediate)
Attacks the CD4 lymphocytes
- type of WBC required for immunity against bacteria, viruses, and parasites
How does HIV attack CD4 cells (2)
Progressive depletion of CD4 cells due to
- Decrease production
- Increase destruction
What is the HIV life cycle (6)
- Attachment and fusion
- HIV will bind CD4 cell
- Capsid (genetic material) released into cell and nucleus - Reverse transcription
- HIV’s reverse transcriptase converts single-stranded HIV RNA into double-stranded DNA - Integration
- Integrase hides virus DINA into host DNA in a loop
- Becomes a pro-virus (can remain dormant for years) - Transcription and translation
- When provirus is activated, RNA polymerase will begin making virus DNA into RNA
- Long viral proteins are made - Assembly
- Proteases will chop up virus protein chains into smaller individual proteins
- Small proteins come together to make new HIV particles - Budding
- New virus particle will exist cell via budding (taking part of CD4 human membrane with it) - destroys CD4 human cell
How is HIV transmitted?
What must it come in contact with
Bodily fluids
- Blood
- Breast milk
- Vaginal fluids
- Semen
- pre-seminal fluid
- Rectal fluids
Must come in contact with
- Mucous membrane
- A damaged tissue
- Injected in blood stream
How is HIV not transmitted
- Air or water
- Saliva, sweat, tears, closed-mouth kissing
- Insects or pets
- Sharing toilets, food, or drinks
What is the usual range of CD4 for those w/o HIV infection
500-1200 cells (~800)
What is the danger zone of CD4 counts where opportunistic infections can prevail
<200 cells
T/F You can have HIV without Aids
True
- AIDS is the last stage of the HIV disease
What does having AIDs means? (2)
- CD4 count <200 cells (or CD4% <14%)
OR
Presence of an AIDs-defining condition
(candidiasis, lymphoma, pneumonia)
What is the presentation of acute HIV infection? (7)
Onset?
- Fever
- Fatigue
- Swollen lymph nodes
- Sore throat
- Muscle/joint pain
- Maculopapular rash on the trunk
- Night sweats
Within 2-4 weeks after exposure
What does the RNA test determine?
HIV viral load
What does the HIV p24 antigen determine
Viral protein that makes the HIV core
- useful for diagnosing EARLY infection (acute) when antibody levels are below detection limits
Which antibodies does the HIV antibody test for? (2) What is the onset?
IgM antibodies
- produced after exposure to an infection
- ~3 weeks
IgG antibodies:
- A later response to infection
- ~infection
What does the 4th generation HIV antibody test for?
HIV antigen AND p24 antigen (sooner detection ~ 16 days)
What are the current recommendations for HIV testing in order (3)
- 4th gen test (HIV antibody + p24 antigen)
- Differentiation immunoassay (HIV-1 or HIV-2)
- If negative/intermediate, perform a NAT (PCR) - detects HIV RNA or DNA in WBCs
What do the Point of Care HIV rapid test detect?
What is the recommendation of when to test?
Detects HIV antibodies ONLY (3rd gen)
Test at baseline, 3 weeks, 6 weeks, 3 months
When was triple therapy and viral load testing discovered
1996
What are the goals of HIV drug therapy (5)
- Suppress HIV replication
- <40 copies/mL - Restore/preserve immune system
- aim for absolute - Reduce HIV-associated morbidity
- Prolong duration and quality of survival
- Prevent HIV transmission
Which surrogate markers are good indicators of treatment response? (2)
Onset?
Statistically significant values?
HIV RNA/HIV Viral load
- less HIV RNA after starting treatment (dec risk of progression to AIDs or death)
- Minimal statistically significant HIV RNA change is 3-FOLD
- Should have viral suppression 8-24 weeks after treatment (if adherent)
Protease inhibitor may take up to 24 weeks
Which surrogate marker is an indicator of immune function in PLWH?
What response do you expect in an older age or a low CD4 count patient with this surrogate marker?
CD4 count
- strongest predictor of disease progression and survival
- important for starting prophylaxis for opportunistic infection
- assess urgency to initiate antivirals
If low CD4 count at baseline or OLDER AGE
- a blunted increase in CD4 counts (despite antivirals)
T/F A poor CD4 response in a patient with viral suppression is an indication to modify ARV
False
What is a significant change between 2 tests in CD4 counts considered? (2)
30% change in absolute count
OR
Change in CD4% by 3%
What was the final outcome of the HPTN trial when they looked at HIV transmission between sero-discordant couples?
Early ARV in HIV positive partner reduced HIV transmission by 96% in sero-discordant couples
How did the START and TEMPERANO trial shape our treatment
A beneficial effect of immediate ART was evident for BOTH
serious AIDS-related
and non-AIDS related events
**NO increased rate of ADRs assosicated with this strategy
T/F starting ARTs early is associated with a trend for decreased likelihood of loss to follow-up and death
True
What is the worldwide ideal recommendation for when to start ARTs?
Ideally within 7 days, including same day
OR
At first clinic visit if patient is ready (financially) and no suspicion of opportunistic infection
When would we delay starting ARVs (3)
- No opportunistic infections at time of diagnosis (CD4 <200), can cause IRIS
- Patient has coverage for drug
- Patient is willing/ready to start (do not want to promote resistance)
What is IRIS (immune reconstitution inflammatory syndrome)
What is its variability of early complication of ART initiation depend on? (4)
Abnormal inflammatory and clinical deterioration
Geography
baseline morbidity
Degree of immunosuppression
- Lower CD4 count = greater risk of IRIS
Associated opportunistic infection
- CNS TB infection
- Cryptococcal meningitis
Prevention strategies of IRIS (3)
- optimize ARV initiation
- Screen for and treat OIs prior to ART
- OI prophylaxis in advanced HIV infection
What are treatment strategies for IRIS (3)
- Optimal treatment of underlying pathogen
- Supportive measure
- Immunosuppression with corticosteroids
**DO NOT STOP/HOLD TREATMETN FOR IRIS
- treat through it
How often do you monitor viral load VL
Baseline
Repeat in 6 weeks
Then every MONTH until undetectable
once undetectable, check every 3-6 months
How often do you monitor CD4 cells at baseline if
CD4 <300
CD4 300+
When do you stop checking
CD4 <300
- q3 months
CD4 300+
- q6 months for 2 years
- if VL undetectable test YEARLY
Stop once:
VL undetectable and CD4 500+
Define Blips in VL
Can occur due to missed dose (adherence issues), during sickness
Can drive resistance
- esp if 1st gen INSTI (3rd gen is more tolerant to resistance)
What is low-level viremia considered
HIV VL of 40-200 copies/mL
- could be that there is a mutation and the drug is not quite effective enough
Define Virologic failure levels
unable to achieve/maintain VL <200
DO RESISTANCE TESTING
When to test do drug resistance testing
Timing of test?
What levels of VL does it work best in?
When to test
- baseline
- ART initiation
- upon virologic failure
Timing
- need to be on an ART within 4 weeks
Works best when VL copies 250+/mL
T/F resistance test will not provide useful information if not done within 4 weeks of ART
False
- just need to recognize that previously selected resistance mutations can be missed
- results from prior resistance testing can be helpful in constructing a new regimen
What does the following adherence levels mean for resistance and transmission
Non-adherence
Intermediate adherence
Near-perfect adherence
No adherence:
- Ongoing replication of wild-type HIV -> patient can transmit wild-type HIV
Intermediate adherence:
- selection for drug resistant HIV -> patient can transmit drug-resistant HIV
Near-perfect adherence:
- No development of drug resistance -> near-complete interruption of transmission (“treatment as prevention”)
What else should be checked when testing for HIV
Due to shared routes of transmission,
If checking for HIV, should also check for Hep A and Hep B (which would also check for Hep D)
