HIV: pathophysiology and presentations Flashcards
What can HIV cause/lead to?
AIDS - Acquired Immunodeficiency Syndrome
Opportunistic infections
AIDS-related cancers
What is the life expectancy of people with HIV?
“near normal”
What is HIV?
A retrovirus
Describe HIV-1
Originated in Central/West African chimpanzees
Responsible for pandemic starting in 1981
Describe HIV-2
Originated in West African Sootey mangabey (Simian ID virus)
Less virulent
What is CD4?
CD4+ receptors are the target site for HIV
A glycoprotein found on the surface of a range of cells
What cells are CD4 receptors found on?
T helperlymohocytes (CD4+ cells)
Dendritic cells
Macrophages
Microglial cells
What do CD4+ Th lymphocytes do?
Essential for induction of adaptive immune response
Recognition of MHC2 antigen-presenting cell
Activation of B-cells
Activation of cytotoxic T-cells (CD8+)
Cytokine release
What does HIV do to the immune response?
Reduced circulating and proliferating of CD4 cells
Dysregulation expression of cytokines
Increased susceptibility to viral infections
Reduced affinity of antibodies produced
What are HIV sufferers susceptible to?
Viral infections
Fungal infections
Mycobacterial infections
Infection-inducing cancers
What is the normal range of CD4+Th cells?
500-1600 cells/mm*3
What number of CD4+Th cells give risk to opportunistic infections?
<200 cells/mm*3
Describe HIV viral replication?
Rapid replication in early and late infection
New generation every 6-12 hours
What is the prognosis of HIV without treatment (on average)?
9-11 years
How does the infection take place?
Infection of mucosal CD4 cell (Langerhans and Dendritic cells
Transport to regional lymph nodes
Infection established within 3 days of entry
Dissemination of virus
How long after infection does it take for symptoms to present?
Usually 2-4 weeks
What are the symptoms of a primary HIV infection?
Fever Rash (maculopapular) Myalgia Pharyngitis Headache/ aseptic meningitis
What occurs in asymptomatic HIV infection?
Ongoing viral replication
Ongoing CD4 count depletion
Ongoing immune activation
Risk of transmission
What is the definition of an Opportunistic infection?
An infection caused by a pathogen that does not normally produce disease in a healthy individual. But does when afforded the opportunity by a weakened immune system.
What organism causes Pneumocystis pneumonia and what CD4 count is needed for this?
Organism - Pneumocystis jiroveci
CD4 count: <200
What are symptoms and signs of Pneumocystis pneumonia
Symptoms: insidious onset, SOB, dry cough
Signs: Exercise desaturation
How do you diagnose Pneumocystis pneumonia?
BAL and immunoflourescence +/- PCR
What is the treatment and prophylaxis for Pneumocystis pneumonia?
Treatment: High dose co-trimoxazole (+/- steroid)
Prophylaxis: Low dose co-trimoxazole
What other opportunistic infection that effects the respiratory system can occur in HIV?
TB
What organism causes Cerebral Toxoplasmosis and what CD4 level is needed?
Organism: Toxoplasma gondii
CD4 level: <150
What is cerebral toxoplasmosis?
reactivation of latent infection
Multiple cerebral abscess (Chorioretinitis)
What are symptoms/signs of cerebral toxoplasmosis?
Headache Fever Focal neurology Seizures Reduced conscioussness Raised ICP
What organism causes Cytomegalovirus and what CD4 count is needed?
Organism: CMV
CD4 level: <50
What is CMV?
Reactivation of latent infection.
What are causes of CMV?
Retinitis
Colitis
Oesophagitis
How does CMV present?
Reduced visual acuity
Floaters
Abdo pain, diarrhoea, PR bleeding
When is screening for CMV done?
Individuals with a CD4 level of <50
What skin infections can occur with HIV?
Herpes zoster Herpes simplex HPV Penicilliosis Histoplasmosis
What is HIV-associated neurocognitive impairment?
Caused by HIV-1
Any reduced CD4 level
How does HIV-associated neurocognitive impairment present?
Reduced short term memory
+/- motor dysfunction
What is Progressive multifocal leukoencephalopathy?
Caused by JC virus
CD4 level of <100
How does Progressive multifocal leukoencephalopathy present?
Rapidly progressing
Focal neurology
Confusion
Personality change
List some other neurological presentations of HIV?
Distal sensory polyneuropathy Mononeuritis multiplex Vacuolar myelopathy Aseptic meningitis Guillan-Barre syndrome Viral meningitis (CMV, HSV) Cryptococcal meningitis Neurosyphilis
What causes kaposi’s Sarcoma and what is it?
Human Herpes virus 8 (HHV8)
Vascular tumour
What CD4 level is needed for Kaposi’s sarcoma?
Any reduced level
How does Kaposi’s sarcoma present?
Cutaneous
Mucosal
Visceral - pulmonary, GI
How do you treat Kaposi’s sarcoma?
HAART
Local therapies
Systemic chemotherapy
What organisms cause non-Hodgkins lymphoma and what CD4 level is needed?
EBV (Burkitt’s lymphoma), primary CNS lymphoma
Any reduced CD4 level
What is the presentation of non-Hodgkins lymphoma?
More advanced B symptoms Bone marrow involvement Extranodal diseaee Increased CNS involvement
What is the diagnosis and treatment of non-Hodgkins lymphoma?
Diagnosis - Same as HIV
Treatment: Same as HIV + HAART
What organism causes Cervical cancer?
HPV
What is cervical cancer?
Rapid progression to severe dysplasias and invasive disease
Name some non-OI of symptomatic HIV
Mucosal candidiasis Seborrhoeic dermatits Fatigue + diarrhoea Worsening psoriasis Lympadenopathy parotitis
What causes haematologic manifestations?
HIV
OI’s
AIDS - malignancies
HIV drugs
What are haematological manifestations of HIV?
Anaemia
Thrombocytopenia
What CD4 level is needed for haematological manifestations to present?
Any reduced CD4 level
What factors increase the risk of HIV transmission?
Anoreceotive sex
Trauma
Genital ulceration
Concurrent STI
What ways can a mother pass HIV on to her child?
In utero/trans-placental
Delivery
Breast-feding
What is the prevalence of HIV in the UK?
1.5/1000
How many people are living with diagnosed HIV in Tayside?
366
What markers of HIV are used in labs to detect infection?
RNA (viral genome) Envelope proteins (gp120) Capsule protein (p24)
When were HIV antibody tests first introduced?
1985
What is the window period for HIV antibody testing?
~63 days
What antibodies are detected in 3rd generation HIV?
IgG and IgM
What is the window period for 3rd generation HIV antibody testing?
~average of 20-25 days
Describe 4th generation HIV tests
Combined antibody and antigen (p24)
Shortens window period by ~5 days (around 14-28 days)
Variability between assays and between labs
What is POCT?
A rapid HIV test
results in 20-30 mins
3rd generation (ab only)
4th generation (ab/ag)
What are the advantages of POCT?
Simple to use No lab needed No venepuncture needed No anxious wait Reduce follow up Good sensitivity
What are the disadvantages of POCT?
Expensive -£10 Quality control Clinical governance Poor +ve predictive value in low prevalence settings Not suitable for high volume Cant be relied on in early infection
What does RITA stand for?
Recent Infection
Testing Algorithm
Describe RITA?
Used to identify if an infection occured within the preceeding 4-6 months
Measure different types of antibodies or strength of antibody binding
What are the advantages of RITA?
Surveillance Local epidemiology Assess HIV testing programmes Inform partner notification Safer sex advice Interpretation of CD4
What are the disadvantages of RITA?
Accuracy
Patient distress
Criminilisation
