HIV Flashcards
What is HIV?
Retrovirus
HIV-2 originated in West African Sootey mangabey
Less virulent
HIV-1 originated in Central/West African chimpanzees: HIV1 group M responsible for global pandemic
What is the target site for HIV?
CD4+ receptors
What cells are CD4+ receptors found on?
T helper lymphocytes
Dendritic cells
Macrophages
Microglial cells
What do CD4+Th lymphocytes do?
Essential for induction of adaptive immune response Recognition of MHC2 APC Activation of B cells Activation of cytotoxic CD8+ T cells CK release
What effect does HIV infection have on immune response?
Sequestration of cells in lymphoid tissues
-Reduced circulating CD4+ cells
Reduced proliferation of CD4+ cells
Reduction CD8+ (cytotoxic) T cell activation
-Dysregulated expression of cytokines
-Increasing susceptibility to viral infections (including HIV)
Reduction in antibody class switching
-Reduced affinity of antibodies produced
Chronic Immune Activation (microbial translocation)
What does HIV increase susceptibility to?
Viral infections
Fungal infections
Mycobacterial infections
Infection-induced cancers
At what CD4+Th count is there a risk of opportunistic infection?
<200cells/mm3
Normal is 500-1600
Describe HIV viral replication
Rapid in very early and very late infection
New generation every 6-12hours
How does HIV spread in the body?
Infection of mucosal CD4 cell (Langerhans/dendritic)
Transport to RLNs
Infection established within 3 days of entry
Dissemination of virus
When is the usual onset of HIV?
2-4wks after infection
What are the common symptoms of primary HIV infection?
Fever Rash (maculopapular) Myalgia Pharyngitis Headache/aseptic meningitis Up to 80% present with symptoms
What happens during the asymptomatic HIV infection?
Ongoing 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 individual. It uses the “opportunity” afforded by a weakened immune system to cause disease
What organism causes pneumocystis pneumonia?
Pneumocystis jiroveci
What are the symptoms and signs of pneumocystis pneumonia?
Insidious onset
SOB
Dry Cough
Exercise desaturation
How is pneumocystis pneumonia diagnosed?
CXR: May be normal, interstitial infiltrates, reticulonodular markings
BAL and immunofluorescence +- PCR
What is the treatment and prophylaxis for pneumocystis pneumonia?
Rx- High dose co-trimoxazole (+- steroid)
Proph: Low dose co-trimoxazole
What tuberculosis infections/conditions are more common in HIV+ than HIV- individuals?
Symptomatic primary infection Reactivation of latent TB Lymphadenopathies Miliary TB Extrapulmonary TB Multi-drug resistant TB Immune reconstitution syndrome
What organism causes cerebral toxoplasmosis?
Toxoplasma gondii
What happens in cerebral toxoplasmosis?
Reactivation of latent infection
Multiple cerebral abscess (chorioretinitis)
What are the symptoms/signs in cerebral toxoplasmosis?
Headache Fever Focal neurology Seizures Reduced consciousness Raised intracranial pressure
What does CMV cause?
Retinitis, colitis, oesophagitis
How does CMV present?
Reduced visual acuity Floaters Abdo pain Diarrhoea PR bleeding
What skin infections can be due to HIV?
Herpes Zoster: Multidermatomal, Recurrent
Herpes Simplex: Extensive, Hypertrophic, Aciclovir resistant
Human papilloma virus: Extensive, Recalcitrant, Dysplastic
Penicilliosis
Histoplasmosis
What causes HIV-associated neurocognitive impairment?
HIV-1
How does HIV-associated neurocognitive impairment present?
Reduced STM
+- motor dysfunction
What causes progressive multifocal leukoencephalopathy?
JC virus
Reactivation of latent infection
How does progressive multifocal leukoencephalopathy present?
Rapidly progressing
Focal neurology
Confusion
Personality change
What are 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 HIV-associated wasting aka Slim’s Disease?
Metabolic (chronic immune activation)
Anorexia (multifactorial)
Malabsorption/diarrhoea
Hypogonadism
What causes Kaposi’s sarcoma?
Human herpes virus 8 (HHV8)
What is the basic pathology of Kaposi’s sarcoma?
Vascular tumour
How does Kaposi’s sarcoma present?
Cutaneous
Mucosal
Visceral- pulmonary, GI
What is the treatment for Kaposi’s sarcoma?
HAART
Local therapies
Systemic chemotherapy
What causes Non-Hodgkins lymphoma?
EBV (Burkitt’s lymphoma, primary CNS lymphoma)
How does Non-Hodgkins lymphoma present?
More advanced B symptoms Bone marrow involvement Extranodal disease Increased CNS involvement
What should be offered to all with complicated HPV disease?
HIV testing
How can cervical cancer present?
Recalcitrant warts
High grade CIN, VIN, AIN, PIN
What are the clinical features of non-OI symptomatic HIV?
Mucosal candidiasis Seborrhoeic dermatitis Diarrhoea Fatigue Worsening psoriasis Lymphadenopathy Parotitis Epidemiologically linked conditions: STIs, Hepatitis B, Hepatitis C
What are some haematologic manifestations of HIV?
Anaemia
Thrombocytopenia
What are the modes of transmission of HIV?
Sexual
Parenteral
Mother to Child
What factors increase transmission risk of HIV in sex?
Anoreceptive sex
Trauma
Genital ulceration
Concurrent STI
How does parenteral transmission of HIV occur?
Injection drug use (sharing ‘works’)
Infected blood products
Iatrogenic
How does MTCT of HIV occur?
In utero/trans-placental
Delivery
Breast-feeding
What is the sex ratio of HIV?
2.1:1 M:F
What risk group has the highest proportion of HIV in the UK?
MSM
What services include an opt-out HIV test?
TOP services GUM Drug dependency services Antenatal services Assisted conception services
What high risk groups should regular HIV screening be carried out on?
MSM Female partners of bisexual men IVDU Partners of people living with HIV Adults, children, sexual partners, and people with history of iatrogenic exposure from/in an endemic area
What are the high prevalence areas of HIV?
Sub-Saharan Africa
Caribbean
Thailand
When HIV falls within the DDx what should be performed regardless of risk factors?
HIV test
Risk assessment not necessary
What is important when taking an HIV test of an incapacitated person?
Only test if in patients best interest
Consent from relative not required
If safe, wait until patient regains capacity
Obtain support from HIV team if required
Which markers of HIV are used by labs to detect infection?
RNA (viral genome) Envelope proteins (gp120) Capsule protein (p24)
What do 3rd generation HIV tests detect?
HIV 1+2 antibody
IgM
IgG
What is the window period of 3rd generation HIV tests?
Avg. 20-25 days
What do 4th generation HIV tests detect?
Combined antibody and antigen (p24)
What is the window period of 4th generation HIV tests?
14-28 days
What is the recent infection testing algorithm?
Can be used to identify if an infection occurred within the preceding 4-6months
How does RITA work?
Measure different types of antibodies or strength of antibody binding- HIV1, subtype B
What are the targets for anti-retroviral drugs?
Reverse transcriptase Integrase Protease Entry: fusion, CCR5 receptor Maturation
What was shown to have in vitro activity against HIV?
Nucleotide analogues reverse transcriptase inhibitors (NRTI) e.g. zidovudine
What is highly active anti-retroviral therapy (HAART)?
A combination of three drugs from at least 2 drug classes to which the virus is susceptible
What is most important in preventing drug resistance in HIV?
Adherence
What are the S/Es of HAART?
GI S/Es (protease inhibitors), transaminitis, fulminant hep (nevirapine, most others)
Skin: rash, HS, SJS (abacavir, nevirapine)
CNS: mood, psychosis (efavirenz)
Renal: proximal renal tubulopathies (tenofovir, atazanavir)
Bone: osteomalacia (tenofovir)
CVS: increased MI risk (abacavir, lopinavir, maraviroc)
Haematology: anaemia (zidovudine)
What enzymes do protease inhibitors interact with?
Liver enzyme inhibitors
What enzymes do NNRTIs interact act with?
Liver enzyme inducers
Describe partner notification and disclosure in HIV
Voluntary process- may takes weeks, months, years
Duty of care to a known third party
How can you prevent onward HIV sexual transmission?
Condom use HIV treatment STI screening and treatment Sero-adaptive sexual behaviours Disclosure Post-exposure prophylaxis Pre-exposure prophylaxis
What are conception options for an HIV+ male, HIV- female?
Timed unprotected sex with HAART
Treatment as Prevention
What are conception options for an HIV+ female, HIV-male?
? Self-insemination
Timed unprotected sex with HAART
Treatment as Prevention
How can you prevent mother to child transmission?
HAART during pregnancy Vaginal delivery if undetected viral load Caesarean section if detected viral load 4/52 PEP for neonate Exclusive formula feeding
