HIV Flashcards
How is HIV spread?
- Sexual transmission
- Injection drug misuse
- Blood products
- Vertical transmission
- Organ transplant
When can a patient be tested for HIV without giving consent?
Unconscious patients can be tested if you think it is in the patient’s best interest
What does the HIV do?
Infects and destroys cells of the immune system especially Th cells that have CD4 receptors on their surface
Where are CD4 receptors found?
- Lymphocytes
- Macrophages
- Monocytes
- Cells in the brain and skin
- Other
What happens in HIV?
- CD4 count declines & HIV viral load increases
- Increasing risk of developing infections and tumours
- The severity of these illnesses is greater the lower the CD4 count (normal CD4 > 500)
When are most AIDS diagnoses made?
When the CD4 count <200
What is the pragmatic approach to HIV?
Consider symptomatic and asymptomatic disease
What is clinical stage 1 of HIV?
- Asymptomatic
- Persistent generalised lymphadenopathy
What is clinical stage 2 of HIV?
- Weight loss
- Minor mucocutaneous manifestations
- HZV infection
- Recurrent URTI
What is clinical stage 3 of HIV?
- Significant weight loss
- Unexplained chronic diarrhoea
- Unexplained prolonged fever
- Thrush
- Oral hairy leukoplakia
- Pulmonary TB
- Severe bacterial infections
What is clinical stage 4 of HIV?
- Wasting syndrome
- Encephalopathy
- Progressive multifocal leukoencephalpathy
- Cryptococci’s, extrapulmonary
- Many others…
What types of infection are you more prone to with a CD4 count <350?
- Thrush
- Skin changes
What types of infection are you more prone to with a CD4 count<200?
- PCP
- TB
- Cryptosporidiosis
- Kaposis lymphoma
- Toxoplasmosis
- Cryptococcal meningitides
- CMV MAC
Is it AIDS or HIV?
- Certain infections and tumours that develop due to a weakness in the immune system are classified as AIDS illnesses. If you have no symptoms then you have HIV infection only.
- Virtually everyone with an AIDS illness should recover from it and then be put on antivirals to keep them free from any future illness.
Respiratory: AIDS defining conditions
- TB
- Pneumocystis
Neurology: AIDS defining conditions
- Cerebral t toxoplasmosis
- Primary cerebral lymphoma
- Cryptococcal meningitis
- Progressive multifocal leucoencephalopathy
Dermatology: AIDS defining conditions
Kaposi sarcoma
Gastroenterology: AIDS defining conditions
Persistent cryptosporidiosis
Oncology: AIDS defining conditions
NH lymphoma
Gynaecology: AIDS defining conditions
Cervical cancer
Ophthalmology: AIDS defining conditions
Cytomegalovirus retinitis
What is the natural history of HIV?
- Acute infection: seroconversion
- Asymptomatic
- HIV related illnesses
- AIDS defining illness
- Death
What happens when HIV antibodies first start to develop?
Primary HIV/Seroconversion
- Approximately 30 - 60% of patients have a seroconversion illness
- Abrupt onset 2-4 weeks post exposure, self limiting 1-2 weeks
- Symptoms generally non-specific and differential diagnosis includes a range of common conditions (can present like glandular fever)
What do symptoms of seroconversion include?
- Flu-like illness
- Fever
- Malaise and lethargy
- Pharyngitis
- Lymphadenopathy
- Toxic exanthema
What is the treatment for HIV?
- Not currently curable
- Combined ART taken as a combined pill once a day
What are the principles of antiretroviral therapy?
- Different classes of drugs acting on different stages in HIV lifecycle
- Combination antiretroviral therapy (cART) means at least 3 drugs from at least 2 groups
- Adherence needs to be over 90% - support patient
- cART can lead to a normal life but side effects can be significant eg metabolic, lipodystrophy,
Where do the treatments act?
- Reverse transcription inhibitors
- Integrase inhibitors
- Protease inhibitors
When should ART be commenced?
-Consider starting all patients at diagnosis regardless of CD4
If CD4 < 350 cells/mm3 encourage patients to start treatment
-If CD4 < 200 need to start as soon as possible
-Any pregnant woman:start before third trimester
What should pregnant women know about their delivery?
They can have a vaginal delivery if their viral load is undetectable
What ART is first line?
Three drug combination with treatment adjustment if VL not adequately suppressed after 4-6 weeks of therapy
What is the current life expectancy?
Life expectancy according to CD4 Nadir (lowest CD4 before starting therapy) in patient diagnosed aged 20
- CD4< 100 age 52
- CD4 100-200 age 62
- CD4 >200 age 70+
How long must patients be on treatment?
- Once treatment is started it must be maintained for the rest of life.
- It may need to change from time to time
- Always a need fro antiviral therapy
Why do treatments fail?
Poor adherence leads to viral mutation and resistance
Incomplete suppression
- Inadequate potency
- Inadequate drug levels
- Inadequate adherence
- Pre-existing resistance
What types of antiviral drugs are there?
- Nucleoside reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase
- Protease inhibitors
- Integrase inhibitors
What are the possible side effects of nucleoside reverse transcriptase inhibitors?
- Lipodystrophy
- Marrow toxicity
- Neuropathy
What are the possible side effects of non-nucleoside reverse transcriptase inhibitors?
- Skin rashes
- Hypersensitivity
- Drug interactions
What are the possible side effects of protease inhibitors?
- Lipodystrophy
- Drug interactions
- Diarrhoea
- Lipodystrophy
- Hyperlipidaemia
What are the possible side effects of integrase inhibitors?
Rashes
How can lipodystrophy be treated
Change drugs (less likely with newer agents)
Cosmetic procedures
- Facelift
- Liposuction
- Fillers
What are the challenges of HIV care in 2018?
- Osteoporosis
- Cognitive impairment
- Malignancy
- Cerebrovascular disease
- Renal disease
- Ischaemic heart disease
- Diabetes mellitus
- The ageing patient
How can HIV be prevented?
- Behaviour change and condoms
- Circumcision
- Treatment as prevention (VL undetectable = untransmissable (pregnancy))
- Pre-exposure prophylaxis (PrEP)
- Post-exposure prophylaxis for sexual exposure (PEPSE)
What is the future of HIV care?
- Therapeutic vaccines
- Long-acting injectable drug treatments
- Cure – “kick-kill” strategies
What is the epidemiology of HIV in Europe?
- M > F
- Variation between countries as to predominant route of spread
- UK is a low prevalence area
What is the main route of transmission within the UK?
- Sexual
- Transmission by IVDU is actually <1% in the UK
What is the predominant form of HIV?
HIV-1
Describe the basic virology of HIV?.
- HIV-1 attaches to cells with CD4 on surface (Th) lymphocyte cells with certain chemokine receptors
- Integrase facilitates integration into host cell DNA
- Contains protease enzyme, needed for mature virus progeny
How is virus diversity produced?
- Retroviruses use reverse transcriptase to convert RNA to DNA
- There is lack of accuracy during replication fiving rise to virus diversity
What family does HIV belong to?
A group of retroviruses called lentiviruses
What does the virus require for replication?
- Host cell
- RNA must be transcribed into DNA
What is the genome of retroviruses made of?
2 single chains of RNA
What specific form of HIV is responsible for the global HIV epidemic?
HIV-1 Group M
Briefly describe how a virus replicates?
- Binding and entry to host cell
- Reverse transcription
- Integration
- Transcription
- Assembly
- Release and protease
What is type of testing is used to diagnose HIV?
Antibody/antigen testing
Why are lab tests carried out in the management of HIV infection?
- Viral load
- HIV resistance testing
- Avidity testing
- Subtype determination
- Tropism testing
- Drug levels
What is the diagnostic window?
- The period of time between exposure and seroconversion when markers of infection (antibodies) are not detectable
- Testing during this period can give false negatives
- Length of window varies
What antibody/antigen testing is carried out?
- 4th generation ELISA assays which allow simultaneous detection of antibody and antigen
- Window period is 1 month
What is HIV genome detection (viral load) used for?
- Used to monitor the effectiveness of HIV treatment
- Used for diagnosis in presence of maternal antibody
- Detection of HIV RNA (range of 40 to >10 million genome copies / ml blood)
How does resistance develop?
- Acute infection
- Chronic infection
- Successful antiretroviral therapy
- Therapy failure
- Treatment interruption
- Salvage therapy and failure
How is HIV resistance testing carried out?
- Sequencing of the polymerase and protease genes
- Identification of specific mutations that confer resistance to antiretroviral drugs
What is HIV resistance testing used for?
- Baseline at diagnosis
- Suboptimal treatment response
- Treatment failing
- Want to change treatment for another reason
What does tropism testing tells us?
Which co-receptor does the virus use to enter CD4 cells, required before using a CCR5 antagonist
What does drug level testing tell us?
Compliance
Do you have to tell your work when diagnosed with HIV?
- If an HIV test is not required for your work then no
- You may need to have an HIV test for a visa to work abroad
- If involved in healthcare, you need to avoid exposure-prone procedures (EPPs) (may not apply if on effective treatment)
How is HIV infection monitored?
- CD4 lymphocyte count
- HIV viral load
- Clinical features
What is the risk of transmisson of BBV to healthcare workers?
Percutaneous exposure (sharp instrument accidentally penetrating the skin) to:
- HBV surface antigen positive blood up to 30% = (1:3)
- HCV RNA positive blood ~ 3% = (1:30)
- HIV positive blood ~ 0.3% = (1:300)
Mucocutaneous exposure (blood or other body fluid splashes into the eyes, nose or mouth or onto broken skin) to: -HIV positive blood <0.1% = (1:1000)
What bodily fluids should be handled with the same precautions as blood?
- Cerebrospinal fluid.
- Pleural, peritoneal, pericardial fluid.
- Breast milk.
- Amniotic fluid.
- Vaginal secretions, semen.
- Synovial fluid.
- Any other body fluid containing visible blood.
- Unfixed tissues and organs.
- Saliva – dental procedures
- Exudate/tissue fluid from burns or skin lesions
What is the risk with HIV and bodies?
-HIV may be recovered for many days after
death.
-Little risk unless leakage of blood or body fluids.
What actions should be taken after blood/body fluid exposure?
First Aid:
- Wash off splashes on skin with soap & running water.
- Encourage bleeding if the skin has been broken
- Wash out splashes in the eye, nose or mouth.
- REPORT to senior manager or doctor AND to OHS.
The risk of infection following blood/body fluid exposure is assed by considering…
- The source of contamination
- The extent of injury and the type of sharp (if any) causing it
- The likelihood of B/C/HIV in the source
- The vaccination history
Ideally the source should be tested with informed consent
How is occupation exposure to HIV managed?
- Should receive post-exposure prophylaxis
- Truvada and Kaltre within 48-72 hours of exposure and continued for 28 days
How should HBV occupation exposure be managed?
- Known responders who have completed course of vaccination= no prophylaxis or a booster
- Non-responders= consider booster and reassure
- Incomplete prophylaxis= complete vaccine schedule, accelerated course if severe risk
How is HCV prevented following occupation exposure?
- No vaccine available
- No immunoglobulin available for PEP
- No anti-viral therapy licenced for PEP
-Early treatment decreases risk of chronic infection →
important to test after exposure
How can exposure to BBV in the health care setting be prevented?
- Good basic hygiene with regular hand washing
- Cover existing wounds or skin lesions
- Take simple protective measure to avoid contamination of person and clothing with blood
- Protect mucous membrane of eyes, mouth and nose from blood splashes
- Prevent puncture wounds, cuts and abrasions in the presence of blood
- Avoid sharps usage
- Safe sharps handling and disposal
- Clear up bodily spillages and disinfect surfaces
- Follow procedure for the safe disposal of contaminated waste
