HIV Flashcards
HIV is a ____virus which causes the ______ ________ ______. ____ related conditions are the single highest predictor of mortality in HIV.
HIV is a retrovirus which causes the acquired immunodeficiency syndrome.
AIDS related conditions are the single highest predictor of mortality in HIV.
Where did HIV originate?
HIV-2 in west African sooty mangabey
HIV-1 in central/west African chimpanzees
Which HIV is responsible for the global pandemic starting in 1981
HIV-1 group M
What is the target site for HIV?
CD4+ receptors
CD4 (cluster of differentiation) is a glycoprotein found on the surface of a range of cells including:
- T helper lymphocytes (CD4+ Cells)
- dentritic cells
- macrophages
- microglial cells
CD4+ Th lymphocytes are essential for….
Induction of adaptive immune response
How is adaptive immune response induced?
- recognition of MHC2 antigen-presenting cell
- activation of B cells
- activation of cyto-toxic T cells (CD8+)
- cytokine release
What effect does HIV infection have on the immune response?
- sequestration of cells in lymphoid tissues
- reduced proliferation of CD4+ cells
- reduction CD8+ (cytotoxic) T cell activatoin
- reduction in antibody class switching
- Chronic immune activation (microbial translocation)
Why does HIV cause Reduction CD8+ (cytotoxic) T cell activation?
- Dysregulated expression of cytokines
Why does HIV vause reduction in antibody class switching?
Reduced affinity of antibodies produced
HIV increases susceptibility to
Viral infections
Fungal infections
Mycobacterial infections
Infection-induced cancersl
What is a normal CD4+ Th Level?
500-1600 cells/mm3
What CD4 level causes risk of opportunistic infections?
<200 cells/mm3
Describe HIV viral replication
Rapid in very early and very late infection
New generation every 6-12 hours
Describe HIV infection pathogenesis?
Infection of mucosal CD4 cell (langerhans and dendritic cell)
Transport to regional lymph nodes
Infection established within 3 days of entry
Dissemination of virus
When do symptoms begin in primary HIV infection
about 2-4 weeks after infection
What are the initial symptoms of primary HIV infection
- fever
- rash
- myalgia
- pharyngitis
- headache/aseptic meningitis
Primary symptomatic HIV infection has what risk of transmission?
Very high risk
Describe what is happening during asymptomatic HIV infection?
Ongoing viral replication
Ongoing CD4 count depletion
Ongoing immune activation
RIsk of onward transmission if remains undiagnosed
What is an opportunistic infection?
An infection caused by a pathogen that does not normally produce disease in a healthy indivdual
What causes pneumocystic pneumonia?
Pneumocystic jirovecci
CD4 threshold <200
What are the symptoms of pneumocystis pneumonia?
Insidious onset;
SOB
Dry cough
What are the signs of pneumocystis pneumonia?
Exercise desaturation
What are the CXR findings in pneumocystis pneumonia and how is it diagnosed?
CXR may be normal- interstitial infiltrates, reticulonodular markings
Diagnosis: BAL and immunofluorescence +/- PCR
What is the treatment for pneumocystis pneumonia?
High dose cotrimoxazole +/- steroid
What is the prophylaxis for pneumocystis pneumonia?
Low dose co-trimoxazole
Which disease shows epidemiological synergy with HIV?
TB
What causes cerebral toxoplasmosis?
Toxoplasma gondii
CD4 threshold <150
Cerebral toxoplasmosis is a reactivation of latent infection (chorioretinitis). It presents with multiple cerebral abscesses.
What are the symptoms/signs;
- headache
- fever
- focal neurology
- seizures
- reduced consciousness
- raised ICP
What causes cytomegalovirus?
CD4 threshold <50
Cytomegalovirus is a reactivation of latent infection;
causes;
Retinitis
Colitis
Oesophagitis
How does cytomegalovirus present?
Reduced visual acuity
Floaters
Abdominal pain, diarrhoea, PR bleeding
Who should be screened for CMV?
All individuals CD4 <50
What skin infections are common in HIV
-
herpes zoster
- multidermatomal
- recurrent
-
herpes simplex
- extensive
- hypertrophic
- aciclovir resistant
-
human papilloma virus
- extensive
- recalcitrant
- dysplastic
-
weird/wonderful
- penicliiiosis
- histoplasmosis
What causes HIV-associated neurocognitive impairment?
HIV-1
What is the CD4 threshold for HIV-associated neurocognitive impairement?
Any increase incidence with increased immunosuppression
How does HIV-associated neurocognitive impairment present?
Reduced short term memory +/- motor dysfunction
What is progressive multifocal leukoencephalopathy?
Caused by JC virus
Reactivation of latent infection
What is the CD4 threshold for progressive multifocal leukoencephalopathy
<100
How does progressive multifocal leukoencephalopathy present?
Rapidly progressing
Focal neurology
Confusion
Personality change
What are the neurological presentations of HIV
- Distal sensory polyneuropathy
- Mononeuritis multiplex
- Vacuolarmyelopathy
- Aseptic meningitis
- Guillan-Barre syndrome
- Viral meningitis (CMV, HSV)
- Cryptococcal meningitis
- Neurosyphilis
What is slim’s disease?
HIV associated wasting
Multiple aetiologies;
- Metabolic (chronic immune activation)*
- Anorexia (multifactorial)*
- Malabsorption/diarrhoea*
- Hypogonadism*
What causes kaposi’s sarcoma?
Human herpes virus 8
What is a kaposi’s sarcoma?
Vascular tumour
What is the presentation and treatment for kaposi’s sarcoma?
Presentation
- cutaenous
- visceral- pulmonary, GI
- mucosal
Treatment
- Highly active antiretroviral therapy (HAART)
- local therapies
- systemic chemotherapy
What causes non-hodgkins lymphoma?
EBV (burkitt’s lymphoma, primary CNS lymphoma)
How does non-hodgkin’s lymphoma present?
More advanced
B symptoms
Bone marrow involvement
Extranodal disease
Increased CNS involvement
How is non-hodgkins lymphoma diagnosed, treated and what is the prognosis?
Diagnosis: as for HIV
Treatment: as for HIV, add HAART
Prognosis: approaching HIV
What causes AIDS related cervical cancer?
Persistence of HPV infection
What are the symptoms of non-oi symptomatic HIV?
Mucosal candidiasis
Seborrhoeic dermatitis
Diarrhoea
Fatigue
Worsening psoriasis
Lymphadenopathy
Parotitis
Epidemiologically linked conditions
- STIs*
- Hepatitis B*
- Hepatitis C*
What causes haematologic manifestation of HIV?
HIV
Opportunistic infections
AIDS malignancies
HIV drugs
What are the haematologic manifestations of HIV?
Anaemia
Thrombocytopenia (ITP)
Sexual transmission accounts for __% of new HIV infections in the UK;
Sex between men __%
Sex between men and women __%
Sexual transmission accounts for 95% of new HIV infections in the UK;
Sex between men 53%
Sex between men and women 42%
What factors increase the risk of sexual transmission of HIV?
Anoreceptive sex
Trauma
Genital ulceration
Concurrent STI
What is parenteral transmission?
Transmission via injecting drugs
Transmission of HIV by parenteral route accounts for _% of new cases in the UK
Transmission of HIV by parenteral route accounts for 2% of new cases in the UK
How is HIV transmitted from mother to child?
In utero/trans-placental
Delivery
Breast-feeding
There is a _ in _ risk at risk babies will become infected with HIV
_ in _ HIV+ infants will die before first birthday if untreated
There is a 1 in 4 risk at risk babies will become infected with HIV
1 in 3 HIV+ infants will die before first birthday if untreated
What is the risk of MTCT in UK over all?
1.2%
<1% if viral load undetected at delivery
In high prevalence areas in the UK (local prevalence >___%) HIV testing is recommended to;
(2)
In high prevalence areas in the UK (local prevalence >0.2%) HIV testing is recommended to;
- all general medical admissions
- all new patients registering at general practice
Where is HIV opt-out testing offered?
TOP services
GUM clinics
Drug dependency services
Antenatal services
Assisted conception services
Which groups should have regular screening?
- MSM
- female partners of bisexual men
- PWID
- partners of HIV+ people
What are high prevalence areas?
Sub-saharan africa
Caribbean
Thailand
How is HIV testing carried out?
- Document consent (or refusal)
- Obtain venous sample for serology
- Request via ICE (accelerate if clinically indicated)
- Ensure pathway in place for retrieving and communicating result
Which markers of HIV are used by labs to detect infections?
RNA (viral genome)- viral RNA
Capsule protein (p25)- antigen
What is seen during seroconversion
3 month period
initial risk and peak of viral load and p24, which then fall as antibody begins to rise
Describe HIV antibody tests
3rd generation
HIV-1 and HIV-2 antibof
Detect IgM and IgG
Very sensitive/specific in established infection
Window period: 20-25 days
What are 4th generation HIV tests?
Combined antibody and antigen (p24)
Shortens window period
What is the window period in 4th generation HIV tests?
13-28 days
variability beteween assays
Variabilit between labs
A negative 4th generation test performed at 4 weeks following an exposure is highly likely to ______ HIV ______
A negative 4th generation test performed at 4 weeks following an exposure is highly likely to exclude HIV infection
What are POCT?
Rapid HIV tests
Fingerprick or saliva
Results in 20-30 minutes
what are the 3rd generation and 4th generation POCT?
3rd- Ab only
4th- Ab/ag
Why is POCT disadvantageous?
Expensive ~£10
Quality control
Poor positive predictive value in low prevalence settings
Not suitable for high volume
Can’t be relied on in ?early infection
What are the targets for anti-retroviral drugs?
- reverse transcriptase
- integrase
- protease
- entry
- fusion
- CCR5 receptor
- Maturation
What is highly active anti-retroviral therapy?
A combination of 3 drugs from at least 2 drug classes to which the virus is susceptible
What is the purpose of highly active anti-retroviral therapy?
- reduce viral load to undetectable
- restore immunocompetence
- reduce morbidity and mortality
How can drug resistance in HIV be prevented?
- adherence!
How does drug resistance in HIV become more likely with poor adherance?
When you are taking your HIV medication correctly, HIV has little chance of getting through
The less you take your medication on time everyday, the weaker the wall becomes
If the wall is too weak HIV learns how to get through.
What are the GI side effects of HAART?
Protease inhibitors
Transaminitis, fulminant hepatitis (nevirapine, most others)
What are the skin side effects of HAART?
Rash, hypersensitivity, stevens-johnsons (abacavir, nevirapine)
What are the CNS side effects of HAART?
Mood, psychosis (efavirenz)
What are the renal side effects of HAART?
Proximal renal tubulopathies (tenofovor, atazanavir)
What are the MSK side effects of HAART?
Osteomalacia (tenofovir)
What are the CVS risks of HAART?
Increased MI risk (abacavir, lopinavir, maraviroc)
What are the haematological side effects of HAART?
Anaemia (zidovudine)
Protease inhibitors are generally potent _____ ______ ______
NNRTIs are generally potent _____ _____ _____
Some drugs require pharmacological boosting (with potent _____ _____ ______)
Protease inhibitors are generally potent liver enzyme inhibitors
NNRTIs are generally potent liver enzyme inducers
Some drugs require pharmacological boosting (with potent liver enzyme inhibitors)
What are common co-infections with HIV and what considerations must be made?
Hepatitis B- same treatment
Hepatitis C- drug interactions
Tuberculosis- drug interactions
Partner notification and disclosure is a _______ process
Partner notification and disclosure is a voluntary process
What are the different strategies for partner notification and disclosure?
Partner referral
Provider referral
Conditional referral
What are the barriers to partner notification and disclosure?
Fear- rejection, isolation, violence
Confidentiality
Stigma
How can sexual transmission of HIV be prevented?
- condom use
- HIV treatment
- STI screening and treatment
- Sero-adaptive sexual behaviours
- disclosure
- post-exposure prophylaxis
- pre-exposure prophylaxis
There is __ risk of transmission of HIV by casual/household contact
no
What are the conception options for sero-discordant HIV + male, HIV - female?
- treatment as prevention
- (+/- timed condomless sex)
- ? HIV PrEP for female partner
What are the conception options for serodiscordant HIV + female and HIV- male?
Treatment as prevention
+/- times condomless sex
self-insemination
?HIV PrEP for male partner
How can transmission of HIV from mother to child be prevented?
- HAART during pregnancy
- Vaginal delivery if undetected viral load
- Caesarean section if detected viral load
- 4/52 PEP for neonate
- Exclusive formula feeding
What is the PrEP eligibility criteria to determine if patient is high risk for HIV?
- HIV+ partner with detectable viral load
- MSM or transwoman
- UPAI >2 partners in 12/12 and likely to do so again in next 3/12
- Confirmed bacterial rectal STI in last 12/12
- Other high risk factor agreed with another clinician
What is the eligibility criteria for PrEP?
- Aged ≥ 16
- HIV negative
- Can commit to 3/12’ly follow up
- Willing to stop if eligibility criteria no longer apply
- resident in scotland
