Week 2 - E - HIV - What, How, WHo, Opportunistic infections, diagnosis Flashcards
What does HIV stand for? WHat does untreated HIV cause?
Human Immunodeficiency virus - HIV
Untreated HIV causes AIDS Acquired immunodeficiency syndrome
What percentage of all deaths of people living with HIV is caused by AIDS?
1/4 of deaths in people living with HIV is caused by aids (due to a late diagnosis of HIV)
Does HIV decrease the life expectancy of patient?
Patients with a diagnosis of HIV have a normal life expectancy - treatment is very good nowadays
HIV 1 and HIV 2 HIV 1 originated in west african most likely by the common chimpanzee HIV 2 originated also in west africa by the sootey mangabey WHich type of HIV is msot widespread worldwide and most infectious?
HIV 1 is more worldwidespread and is more infectious than HIV 2
HIV 1 likely inferred origiin was the common chimpanzee in West africa
What type of virus is HIV?
HIV is a retrovirus
What is a retrovirus?
This is a single stranded RNA virus than once infecting the host cell, it goes back to DNA using its reverse transcriptase enyzme to produce its own DNA copy from its RNA genome
What are the target sitesfor HIV? What are the main cell type that expresses these receptors?
The target cells are the CD4+ receptors
The main cell type expressing these receptors are the T helper lymphocytes (CD4+ cells)
What cells other than the T helper lymphocytes express CD4+ receptors?
Dendritic cells
Macrophages
Microglia
T helper lymphocytes express the CD4+ receptors and HIV binds to the CD4+ receptors and then enters the lymphocytes WHat is CD4+ again? What cells express the CD4+ recpetors?
It is a glycoprotein found on the surface of a range of cells
- T helper lymphocytes
- Dendritic cells
- Macrophages
- Microglia
What do CD4+ Th lymphocytes do?
These cells are essential for the adapative immune response - specific immune response
Adaptive immunity also includes a “memory” that makes future responses against a specific antigen more efficient.
What is the non-specific immune response that comes to play within hours of the ntigen presenting itself to the body?
This is the innate immune response
CD4 cells (These are the T helper lymphcoytes that experess the CD4 receptors) help orchestrate the immune response and recognize the MHC2 APC (antigen presenting cells) WHat do CD4 cells do once the MHC2 antigen presenting cell binds to it? (three things)
- They activate B antibodies
- They activate cytotoxic T cells (CD8+)
- Activate cytokine release
When CD4 cells aren’t working, their can be a lot of problems with the immune system
HIV infection has a big effect on the immune response It causes sequestration of the CD4+ cells in lymphoid tissue - what does this mean?
This means there is an accumulation of CD4+ cells in lymphoid tissue and therefore a reduced circulating CD4+ cells to help fight infection
HIV also causes Reduced proliferation of CD4+ cells Reduction CD8+ (cytotoxic) T cell activation How does it also decrease the affinity of antibodies produced?
It causes a reduction in antibody class switching - therefore cant change the antibody produced so a decrease in the likelihood of antibody combining to the antigen
As stated HIV has many effects on the immune response Reduction in circulating CD4+ cells Reduction in proliferation of CD4+ cells Reduction inCD8+ (cytotoxic T cells) activation Reduction in antibody class switching which reduces the affinity of antibodies produced What does all this make the person more suceptible to?
- Viral infections
- Fungal infections
- Mycobacterial infections
- INfection-induced cancers
What are the normal parameters of CD4+ Thelper lymphocyte cell count? What is the threshold for opportunistic infection?
500-1600 cells/mm3 is the normal parameters for Thelper lymphocyte cell count
Threshold for opportunistic infection is when the count is <200cells/mm3
There is rapid replication in very early and very late HIV infection How often does the HIV virus replicate in early infection?
HIV virus replicates every 6-12 hours in early infection
After being infected with the HIV virus, 80% of people develop symptoms when?
80% of people develop symptoms within 2-4 weeks of being infected with the virus
After the acute HIV stage, what is the next stage in the HIV infection? How long oes the asymptomatic HIV stage tend to last?
This is the asymptomatic HIV infection stage where there is ongoing viral replication without symptoms with a decreasing CD4 cell count
Lasts roughly 8ish years
Early on huge amounts of virus replicated and CD4 count therefore decreases There is then a small immune response to the HIV where the viral load decreasesThen the HIV slowly continues to replicate before AIDS related conditions causes a massive spike in viral load at the end
What is the CD4+ cell count when the aids related condition kicks in? Without treatment,what is the avergate time until death?
Usually below 200cells/mm3
Average time until death is approx 9-11 years without treatment
Commonest transmition is in the mucosal CD4 cells The muscosal CD4 cels take the virus into circulation and transport to regional lymph nodes How long does the virus take to infect the CD4 cells DNA and therefore how long do you have to give post exposure prophylaxis treatment?
The virus takes about 3 days to infect CD4 cells
DNA and therefore have up to 72 hours to start post-exposure prophylaxis treatment 3 days after the virus has established itself into the CD4 DNA, get the huge rapid spike in DNA replication and dissemination of the virus
As stated, up to 80% of people present with symptoms 2-4 weeks after initial infection What are the combination of symptoms in the primarry infection stage?
Most people experience sort of flu like sympotms in this time period
- Fever
- Rash
- Myalgia
- Pharngitis
- Headache
A young woman is contacted by the public health nurse and informed that one of her sexual contacts tested positive for HIV. The young woman comes into the clinic to be tested. She tells the nurse that she has heard that people who are infected with HIV have a period when they test negative even though they are very infectious.
What is this period called? a) infectious stage b) primary infection c) viral set point d) window stage
b) primary infection
What type of rahs appears in the primary infection of HIV? Are people infectious at this stage?
People usually get a widespread maculopapular rash
There is a very high risk of transmission at the primary infection stage
In the asymptomatic phase there is ongoing viral replication causing ongoing CD4 count depletion until opportunistic infection occurs
Define an opportunistic infection Opportunistic infections include - PCP, TB, Toxoplasmosis, Cytomegalovirus, skin infections etc
An infection caused by a pathogen that does not normally cause infection in a healthy individual
It uses the opportunity of a weakened immune system to cause disease
What is the fungus like lung infection that is not commonly found in the lungs of healthy people, but, being a source of opportunistic infection, it can cause a lung infection in people with a weak immune system? It is the most common opportunistic infection in people with HIV infection
This is pneumocystis pneumonia (PCP)
WHat bacteria causes pneumocystic pneumonia? What are the symptoms? What is the CD4 threshold?
Caused by penumocystic jirovecii
Get a dry cough, SOB and oxygen desaturations on exercise
CD4+ threshold is less than 200cells/mm3
How is the diagnosis of PCP carried out? CXR may be normal but when abnormal Get the interstitial infiltrates (can look like cardiac failure but without the cardiomegaly)
Bronchoealveolar lavage (BAL) and immmunoflouresence - this is basically when a fluid is squirted into the lungs via a bronchoscope and then aspirated and examined under immunoflouresence
What is the treatment of pneumocystic pneumonia? WHat is the prophylactic treatment for PCP with anyone who has CD4 count <200cell/mm3?
High dose co trimoxazole treats PCP
Prophylactic treatment would be low dose co-trimoxazole
Where HIV is most common, TB is also pretty common:
- Symptomatic primary infection
- Reactivation of latent TB
- Lymphadenopathies
- Miliary TB
- Extrapulmonary TB
- Multi-drug resistant TB
What syndrome can occur commonly in someone with HIV who gets a TB infection? (hyper immune response)
Immune reconstitution inflammatory syndrome - IRIS
- The suppression of CD4 T cells by HIV (or by immunosuppressive drugs) causes a decrease in the body’s normal response to certain infections
- If the CD4 count rapidly increases (due to effective treatment of HIV), a sudden increase in the inflammatory response produces nonspecific symptoms such as fever, and in some cases a worsening of damage to the infected tissue.
There are a lot of drug-drug interactions in TB and HIV treatment - makes things very difficult What is the normal treatment of TB? State the side effects of the ddrugs?
2 months RIPE - rifampicin, isoniazid, pyrazinamide, ethambutol
4 months RI - rifampicin, isoniazid
- Rifampicin - orange urine/tears
- Isoniazid - neuropathy, hepatitis
- Pyrazinamide - hepaitits and gout
- Ethambutol - optic neuritis (colour vision goes first)
HIV can cause reactivation of toxoplasmosis infection - this infection is lifelong and lies latent but is an opportunistic infection Toxoplasmosis releases trophozoites that migrate mostly to eye, brain and muscle What parasite causes toxoplasmosis? What is the CD4 threshold? What are the signs (CT) and sympptoms?
Caused by toxoplasmosis gondii
CD4 threshold is usually lower than 150cells/mm3
Get focal neuropathy - headaches, seizures, reduced consciousness, raised ICP, fever
Can see multiple cerebral abscesses on CT scan
Cytomegalovirus is usually also a latent infection reactivated when HIV compromises the immune system What is the CD4 threshold here usually? What screening is done for all individuals below this CD4 threshold then? What is this type of human herpes virus?
CD4 threshold is usally below 50 for this infection to occur and therefor all individuals with CD4 count below 50cells/mm3 have retinal screening by ophthalmology as this virus causes retinitis
HHV5 is cytomegalovirus
CMV can cause retinitis, colitis and oesophagitis commonly What are the symptoms of infection usually? What is the treatment?
Symptoms usually include reduced visual acuity and floaters in the eye
Abdo pain and diarrhoea
Treatment is IV ganciclovir
HIV can cause a rage of skin infections Herpes Zoster is usally dermatomal and is treated with acicylovir What is abnromal about the infection in patients with HIV? What is abnromal about herpes simplex in patients with HIV? What is abnromal about HPV in patients with HIV?
Herpes zoster is usually dermatomal and recurrent (HHV 3)
Hepres simplex usually is aciclovir resistant and extensive
HPV is extensive and usually also does not respond to treatment
What is the difference between condyloma acuminatum and condyloma lata?
Condyloma acuminatum is genital warts caused by HPV (usually types 6 and 11 amongst others)
Condyloma lata is very infectious cutenous lesions in the secondary stage of syphilis - usually painless raised lesions
What is the name of the condition (seen in patients who are recieving treatment for multiple sclerosis) that can be seen in patients with HIV disease? Which virus causes it?
This is progressive multifocal leukoencephalopathy
Caused by the JC virus - John Cunningham virus
What are the symptoms of progressive multifocal luekonecephalopathy? What is the main drug used in the treatment of MS that causes this?
PML affects the frontal lobe - behavioural changes and confusion
Also can cause focal neurology depending on what other parts of the brain are infecteed
Tysabri -Natalizumab (monoclonal antibody - 2nd line in treatment of MS) is a drug which can cause this
What is the wasting syndrome linked to HIV known as? It is where there is HIV related cachexia (Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight.)
This is slim’s disease
WHat are three HIV related cancers?
Kaposi’s sarcoma
Non-Hodgkin’s Lymphoma
Cervical cancers (HPV related)
What organism causes kaposi’s sarcoma? What does this sarcoma look like? What is the treatment?
- Kaposi’s sarcoma is caused by human herpes virus 8
- It is a vascular tumour which presents with red/brownish lesions
- Treat the sarcoma by treating the HIV - HAART
EBV can cause Burkitt’s lymphoma and primary CNS lymphoma - both types of non-hodgkin’s lymphoma Usually presents at more advanced HIV What is different about the cancer cells in non-hodgkins and hodgkins lymphoma?
A doctor can tell the difference between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma by examining the cancer cells under a microscope.
If the doctor detects the presence of a specific type of abnormal cell called a Reed-Sternberg cell, the lymphoma is classified as Hodgkin’s.
What organism does HIV make more likely to cause cervical cancers?
This would be human papilloma virus
WHat people are offered the vaccine to HPV?
Females/males aged 11-13
MSM aged up to and including 45 who present in SRH and HIV clinics
Molluscum contagiosum (MC) is a very common benign self-limiting cutaneous viral infection caused by molluscum contagiosum virus. Disease is self-limiting in immunocompetent individuals, while it is severe and prolonged when associated with Human Immunodeficiency Virus (HIV) infection. HIV should be screened for when MC isprolonged and severe What STIs should you screen for HIV in?
If a patient presents with any STI, screen for HIV
How many patients with HIV are found to be anaemic? What type of thrombocyopenia should you give a HIV tests in? (also give test if persistant thrombocytopenia, neutropenia and leucopenia) What is thrombocytopenia?
Anaemia affects up to 90% of patients with a HIV infection
If diagnosing somebody with idiopathic thrombocytopenia then they should be given an HIV test
Thrombocytopenia is when there is a low platelet (Thrombocyte) count
Case study - Alan 27 March 2012 “lethargy, unwell” Macrocytosis (abnormaly large red blood cells), PLT 66 - low ALT 123, GGT 96 - Thought his ALT may be related to the alcohol as when he drinks and stops drinking, the ALT rises and falls respectively Alan had persistent thrombocytopenia, what should have been done?
Should have been off an HIV test
If there is a clinical symptoms of HIV, should have an HIV test regardless of whether you think it was HIV or not His HIV test was positive and CD4 count was 191 What does this CD4 count mean? 8 years prior turns out Alan had had pharnygitis, and a skin rash, what does this show?
This CD4 count means he is at risk of opportunistic infection
This 8 year prior symptoms shows he may have had primary infection symptoms of HIV at the age of 19
What are the three main modes of transmission of HIV?
Sexual transmission
Parenteral transmission
Mother to infant transmission
Sexual transmission is the main way in which HIV is transmitted Why is anoreceptive sex increase the risk of HIV transmission?
This is because there is far more lymphoid tissue in the anus and there is therefore more CD4 cells for the HIV to infect
What are the three stages at which mother to infant transmission can occur?
In utero/trans placental
During delivery (intrapartum)
And by breast milk
Prevalance of HIV in the UK is almost 2 in 1000 people What group of people are mainly the undiagnosed?
It is mainly heterosexual men who remain undiagnosed with a HIV infection
What groups of people have the highest diagnosis rate of HIV? How common is HIV in MSM in the UK?
MSM - 1in20 have HIV (as high as 1in8 men in london)
Black african women are the next highest rate for HIV
Black african men next
Over the past decade, is the proportion of people diagnosed with HIV increasing or decreasing in africa and in the UK?
Proportion of new diagnoses in the UK is increasing
Proportion of new diagnoses in africa is decreasing
MSM is the risk group with highest proportion of HIV in UK 17% of individuals living with HIV in the UK are undiagnosed What group is most likely to be undiagnosed and most likely to present late?
Heterosexual men most likely to be undiagnosed
Heterosexual men most likely to present late
If you come to a sexual and reproductive health clinic you are offered a HIV test In antenatal and assisted conception services, HIV test should be offered as the consequences are unacceptably high What are high prevalence risk groups where regular screening should be offered?
MSM
Females with bisexual partnes
People who inject drugs (PWIDs)
Partners of people living with HIV
When HIV falls within the differential diagnoses an HIV test should be performed regardless of risk factors How is consent for a HIV test obtained?
Explain to the patient they are being offered an HIV test and why
Reassure confidentiality
Explain the benefits of having the test and when they can expect to hear results
Does consent for an HIV test need documented or not?
Consent for an HIV test requires documentation (document if refusal)
What markers of HIV are used by labs to detect infection?
Antibodies, antigens and viral load are used as markers for infection
What is the antigen that that is tested for in HIV?
The HIV p24 antigen
The enzyme-linked immunosorbent assay is a test that uses antibodies and color change to identify a substance - ELISA test WHat is the difference between the third and fourth generation testing for HIV?
Third generation ELISA - tests only for HIV 1 and 2 antibodies
Fourth generation - combined antibody testing and p24 antigen
Third generation ELISA testing has a window period of 20-25 days where the test may result in negative result, how much does the fourth generation testing reduce this window period by?
Fourth generation testing reduces the window period by approx 5 days
When do HIV antibodies usually appear in the blood? How long can it take for the antibodies to appear? Therefore when is the fourth generation testing carried out to check for HIV?
HIV antibodies usually appear in the blood around 4-6 weeks although can take up to 12 weeks to appear
Fourth generation testing is therefore usually carried out at around 4 weeks and then again at 12 weeks to ensure true negative diagnosis - A negative test result at least 4 weeks post-exposure can be reassuring but all people should be offered a further HIV test 12 weeks post-exposure to definitively exclude HIV infection.
Blood tests are one of the four main ways of HIV testing Can also have point of care testing Home sampling kit and Home testing kit WHat is the point of care testing?
Point of care testing is a rapid HIV test where a fingerprick sample or saliva is taken and results are ready within 30 minutes
If the results of a point of care test are positive, does the person definitely have HIV?
If the results are positive a blood laboratory test should be sent for as POCT has a high false positive
Point-of-care tests may also be used in emergency situations such as when an unwell person presents to an Accident and Emergency department, or in community outreach testing and HIV screening pilots in primary care.
Describe the home sampling kit? Describe the home testing kit?
Home sampling kit - where you collect a saliva sample or small spot of blood at home and send it off in the post for testing.
You’ll be contacted by phone or text with your result in a few days
Home testing kit - here you collect a saliva sample or small spot of blood yourself and test it at home.
What are the four HIV tests? Which is most accurate? If the other three test positive, what test should be carried out?
Blood sample testing
Point of care testing - rapid HIV test in clinic
Home sampling kit
Home testing kit
If the other three tests come back positive, carry out a blood smaple test - uses fourth generation ELISA testing to look for combined HIV antibody and p24 antigen
What is important about the p24 antigen?
p24 antigen: this is a core HIV protein and is present during high viral replication
Name some opportunistic infections present in HIV?
- Penumocystic pneumonia - due to pneumosyctis jirovecci - <200cells/mm3 CD4 count
- Tuberculosis
- Cerebral toxoplasmosis - toxoplasmosis gondii - CD4 count <150cells/mm3
- Cytomegalovirus -HHV5- CD4 count <50cells/mm3
- Skin infections - HSV, VZV, HPV
- PML - JC virus - CD4 count <100cells/mm3
- HIV associated cancers (Kaposi’s, non hodgkins, cervical)
What is the treatment of PCP? What is the prophylaxis treatment for PCP? When should PEPSE (post exposure prophylaxis sexual exposure) be given?
Treatment of PCP is hgh dose co-trimoxazole
- Prophlyaxis for PCP should be given if CD4 count less than 200cells/mm3 - low dose co-trimoxazole
PEPSE - given within 72 hours of potenital exposure to HIV for 28 day treatment course
