HIV Flashcards
(47 cards)
1
Q
What type of virus is HIV? Other features
A
Retrovirus
- single stranded
- positive-sense
- enveloped
- genus: Lentivirus
2
Q
What is the main effect of HIV?
A
CD4+ T cell depletion
<500 = AIDS
3
Q
What is HIVs mechanism of attacking CD4+ T cells?
A
- CD4 binding
- Co-receptor binding on chemokine receptor:
- CCR5 OR
- CXCR4 - Fusion, including integration of proviral DNA
- Budding
- Maturation
- New HIV virion
Usually first infect cells like dendritic cells, which will take virus to lymph nodes and cause immune reaction. Infects CD4 T cells and monocytes in lymphoid tissue which go everywhere else.
4
Q
What are the key types/subtypes?
A
HIV1: Group M (A-K) Group N Group O Group P
HIV2
- less virulent/infective/prevalent
5
Q
Transmission
A
- Sex - rectal or vaginal
- IV drugs
- IV infected blood/blood products
- Vertical
- Others
6
Q
Most common symptoms of primary HIV infection (in descending order)
A
- fever
- fatigue
- rash
- headache
- lymphadenopathy
- pharyngitis
- myalgia/arthralgia
- diarrhoea
7
Q
How many cases asymptomatic?
A
40-90%
8
Q
How soon can HIV anti-body be detected?
A
22-27 days post infection
9
Q
How soon can HIV RNA be detected in plasma?
A
1-3 weeks before antibody
10
Q
What is the difference between early (Acute) vs chronic infection?
A
Early:
- CD4+ T cell depletion, especially in gut
- This will then recover quickly
Chronic: Immune activation and inflammation in lymphoid tissues caused by: - Macros/monos - Dendritic cells - CD4+ T cells Slow decrease over time
11
Q
What are the different stages/symptoms?
A
- Seroconversion
- Fever
- Myalgia
- Arthralgia
- Adenopathy
- Malaise
- Rash
- Meningitis - Asymptomatic or non-OI disease
- Thrombocytopenia
- Reactive arthritis
- Polymyositis
- Bell’s Palsy
- CIDP - Mucutaneous OIs
- Deb. dermatitis
- Warts
- Molluscum
- HZV
- HSV
- Candidiasis
- Hairy Leukoplakia
- TB - Severe OIs (AIDS, stage IV)
- Pneumocystosis
- Toxoplasmosis
Cryptosporidosis
- Cryptococcosis
- MAC
- CMV
- Kaposi’s Sarcoma
- Lymphoma
- Cervical Cancer
12
Q
Other pathogens causing disease as a result of HIV-induced immunodeficiency
A
- herpes
- Heps
- HPV
- TB
- Strep pneumoniae
13
Q
What cancers are HIV patients more prone to?
A
- Kaposi’s sarcoma - HHV-8
- Lymphoma - EBV
- Primary cerebral lymphoma - EBV
- Carcinoma of cervix/anus – HPV
- Smooth muscle tumours – EBV
Note: infection-related cancers higher in HIV than transplant recipients
14
Q
Why does HIV make them more prone to these viruses?
A
CD4 T cells – interferon gamma (chronic interferon activation, therefore chronic inflammatory disease) – activate macrophages etc.
If no CD4s, macrophages can’t work Also CD8s can’t work properly – therefor viral infections such as EBV, CMV. Therefore more prone to cancers relating to viruses.
Path:
- HIV Replication
- CD4+ depletion, particularly in GALT (gut associated lymphoid tissue)
- Transloctaion of microbial products from gut AND HIV replication cuases immune activation and inflammation in lymphoid tissue
- This results in depletion of naive T cells, memory B cells and NK cells. B cells persistently stimulated and less likely to deal with pathogens.
- Immune activation/inflammation also results in non AIDS HIV disease:
- atherosclerosis
- osteoporosis
- Type 2 diabetes
15
Q
What neuro diseases can HIV cause?
A
Encephalopathy (brain)
- HIV-associated neurocognitive defect (HAND)
• Dementia when severe
Myelopathy (spinal cord)
- Spastic parapareisis
Neuropathy (peripheral nerves)
- Distal symmetric polyneuropathy (DSPN)
- Mononeuropathy multiplex
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Progressive lumbosacral polyradiculopathy
16
Q
MISC HIV diseases:
A
- Thrombocytopaenia
- Nephropathy
- Primary pulmonary HT
17
Q
What is the problem of HIV latent reservoir?
A
Latent infected CD4+ T cells
They aren’t replicating so can’t be targeted by treatments
18
Q
Effects of smoking and HIV?
A
HIV significantly affects mortality in HIV patients
19
Q
Treatment interruption
A
Results in more hIV and non-HIC associated disease outcomes and death
Meds even reduce things like CVD risk:
- frailty and bone disease
- liver disease
- diabetes
- cognitive decline and dementia risk
- CVD
- Cancer risk
- Immune Senesence
20
Q
Why does HIV affect bone aging?
A
Twice rate of osteopenia and OP due to high bone turnover
Osteoclasts driven by B cell s which are persistently activated in HIV infection.
NOT entirely stopped by treatment
21
Q
How does HIV increase CVD risk?
A
Chronic inflammatory state - vascular and endothelial dysfunction:
- HT
- Atherosclerosis
- MI
This risk is reduced hugely by cessation of smoking but still higher than background population.
22
Q
How does HIV result in poorer fat profile?
A
Due to virus, environment, genetics. Adipose tissue and liver dysfunction: - lipodystrophy - insulin resistance - dyslipidaemia
23
Q
Biomarkers
A
- CD4 T cell counts
- sCD163 - reduced only with aviremic HIV RNA level
- sCD14 - not influenced by any level of HIV RNA level
- CXCL10
24
Q
How effective is HIV treatment?
A
Effectively prevents AIDS
Limitations in preventing systemic inflammation and long term morbidities
25
How due CD4 T cell counts change as disease progresses?
Stage I: Asymptomatic
- Acute phase
- Weeks 0-9
- Large dip and then started ro recover
Stage II: Minor symptoms
- Weeks
- slight recovery in count
Stage III: Moderate symptoms
- Over years
- Count slowly declines
- Stage IV: AIDS
- 8+ years
- faster CD4 Depletion
NOTE: viral load is the inverse of CD4 count
26
What are the indications for HIV testing?
HIV Indicator disease (i.e. test for HIV if they have these diseases):
- Any AIDS defining condition
- TB
- STI
- HBV,HCV
- Lymphomat5
- Head and neck cancer
- Anal and cervical CIN 2+
- Unexplained thrombocytopenia, lymphopenia, neutropenia >4 weeks
- Recurrent/multidermatomal Shingles
- Severe psoriasis
- Severe Dermatitis
- Extensive warts/molluscum contagiosum
- Florid/difficult fungal infections
- Oral candida
- Oral hairy leukoplakia
- Necrotizing gingivitis
- Constitutional symptoms with no other apparent cause
- Mononucleosis type syndrome
- Any unexplained retinopathy
Other indictaions:
- IV drug users
- Partners of these people
- Men who have sex with men, and their female partners
- People from high prevalence countries
- Pregnant women
- Blood products before 1985
27
All asymptomatic MSM (men who have sex with men) should be tested for:
Pharyngeal swab, anorectal swab, first void urine:
- CT and GN
Serology:
- Syphilis
- HIV
- Hep A,B,C
28
How frequently should men be tested?
If any sexual activity in last 12 months:
- At least once a year
If unprotected anal sex, >10 partners in 6 months, group sex, drug use in sex, HIV positive:
- Up to 4 times a year
29
How should anal swab/urine be collected?
- Self collection of anal swab and urine sample is sufficient for asymptomatic patients
30
How is HIV tested?
Combined p24 antigen and HIV 1/2 antibody test on blood
31
Facts about p24 testing:
- The p24 antigen test may become negative 2-6 weeks after exposure, /peaking around 3-4 weeks
- Positive tests are subject to confirmatory tests and sometimes repeat blood collection may be needed e.g. Western blot Rapid test
- It may take 2-3 weeks for symptoms to occur and the p24 and antibody test to become positive
- The great majority of HIV infected patients will return a positive test by 6 weeks post exposure,
- 3 months post exposure remains the recommended time for final testing
32
Patterns of various markers
- /HIV antibodies start to appear in small quantities around 2-3 weeks. Remain elevated forever
- CD4s increase again and then decrease steadily over time
- HIV RNA in blood peaks within first year and then drops, increading again slowly over time
- P24 Ag similar to HIV RNA - peaks within first few weeks (2-3 weeks), then declines sharply, then increases steadily over time again
33
Window periods for serum markers?
HIV RNA:
- 10 days (7-21)
p24 Ag:
-17 days (13-28)
HIV Ab:
- 22 days (18-34 days)
34
/Pre-test counselling for HIV?
- Reason for testing and risk assessment
- Timing of risk and option of post-exposure prophylaxis (PEP)
- Need for other STI and blood-borne virus testing
- History of previous HIV testing
- Confidentiality and privacy issues
o Notifiable disease
o Contact tracing if positive
- Natural history of HIV and transmission info
- Prevention of transmission and risk reduction through behavior change
- Implication of a positive test result, including availability of treatment
- Implications of a negative result
- Explanation of the window period
- General psych assessment and assessment of social supports in event of positive result
- Logistics of tests – time taken for results to become available and method of delivering results
35
Factors contributing to rapid RNA virus evolution?
- Error-prone polymerases
- Lack of proof-reading mechanisms
- Magnitude of replication:
o large burden of infected cells
o generation time
- Selective pressures
o Drugs
o Cellular and anatomic compartments
36
Constraints on RNA virus evolution?
- Requirements for adaptation to multiple tissues or hosts (eg, arboviruses)
- Overlapping reading frames (eg, HBV)
- RNA structure
- Restriction of replication
o Fitness
o Latency
37
Describe HIV1 Drug resistance:
- Bell shaped curve – does not occur at 0 antiviral drug activity or 100% activity – so big problem with missed doses – adherence is a huge problem – literally can’t have any viral replication
- Emergence of drug-resistant virus is an inevitable consequence of the failure to fully suppress HIV-1 replication.
- Drug resistance leads to failure of antiretroviral therapy.
- Using combination therapy prevents drug resistance
- Requirement for high life long adherence
38
What are the most common drug combos?
```
o 2 (NRTI) RT inhibitors (reverse transcriptase) + integrate inhibitor 2 (NRTI)
o RT inhibitors + NNRTI
o 2 (NRTI) RT inhibitors + boosted protease inhibitors
```
39
What are the toxic effects of ART therapies?
```
o Pancreatitis
o Lactic acidosis
o Neuropathy
o Renal calculi
o Subcutaneous fat wasting
o Metabolic syndrome
o Hyperlipidemia
o Systemic drug hypersensitivity syndromes
```
40
Individual patient considerations when choosing antiretroviral drugs
o Adherence potential
o Risk factors for adverse drug effects
• HLA-B5701+ (if this genetic marker is present, then risk) (abacavir hypersensitivity syndrome)
• Renal dysfunction (tenofovir nephropathy)
o Other medical conditions
• TB, liver disease, cardiovascular disease, recreational drug use, pregnancy
o Pregnancy potential in women
o Co-infection with Hepatitis B virus
o Potential for infection by drug resistant HIV
o Potential for interactions between ART and other medications
41
How effective are ART therapies?
- >80% of patients achieve suppression of HIV RNA to undetectable levels in plasma
Only need outpatient care 2-4 times/year
42
ART for prevention?
96% in partners
43
PrEP?
>90%
Reverse transcriptase inhibitors
44
Who are PrEP candidates?
• Men who have sex with men (MSM), transgender individuals, heterosexual men and women, IVDUs At Substantial risk of acquiring HIV infection:
* HIV-positive sexual partner, pre-conception for women
* Recent bacterial STI
* High number of sex partners
* History of inconsistent/no condom use
* Commercial sex work
* High-prevalence area or network
45
Categories of treatment?
- Integrase Inhibitors (Viral DNA needs to integrate)
- Protease Inhibitors (Needed for budding to mature HIV virion)
- Reverse Transcriptase Inhibitors
- Fusion/entry inhibitors (i.e. virus needs to enter cell)
46
What is the SOAP system in reference to HIV?
```
- Subjective
o 1.Does he understand the diagnosis?
o 2.When transmitted?
o 3.Primary HIV?
o 4.AIDS symptoms?
o 5.Past medical issues?
o 6.Current or recent sexual relationships? Mental state
```
```
- Objective
o 1.Vital signs
o 2.Organ systems: - significant positives and negatives
o 3.Mental state
o 4.Results to date
```
- Assessment
o Individual – diagnosis, stage/severity, comorbidities
o Public health implications
```
- Plan
o 1.Further Ix
o 2.Referrals
o 3.Public health
o 4.Mental state
```
47
SPIKES for breaking bad news
- Setup
- Perception – what do they already know? How were they prepared for the test?
- Invitation – Ask if its okay to talk about it (readiness), or in front of their guests
- K knowledge – plain English
- Emotion – be empathetic
- Summarize/strategy
