HIV and AIDS Flashcards
How can HIV be spread?
- Sexual transmission
- Injection drug misuse
- Blood products
- Vertical transmission
- Organ transplant
What does HIV actually do?
Infects and destroy cells of the immune system, especially the T-Helper cells that are CD4+
What are CD4 receptors present on?
- Lymphocytes
- Macrophage
- Monocytes
- Cells within the brain, skin and other sites
What is the natural progression of the pathophysiology of HIV?
CD4 count declines as the HIV viral load increase, this causes:
- Increased risk of infections and tumours
- Increased severity of illness as CD4 count decreases
What is a normal CD4 count?
> 500
When is AIDs diagnosed?
When CD4 count is below 200
What is the correlation of CD4 cunt and infection?
As CD4 count decreases there is an increased risk of infections from opportunistic bacteria
What is the progression of HIV RNA and CD4 count?
1) Initial spike in HIV RNA + Sudden Drop in CD4
2) HIV RNA drastically reduces however CD4 rises slightly
3) HIV RNA plateaus but CD4 count begins to decline gradually
4) HIV RNA sudden spikes and then plateaus, CD4 continues to fall
Stage 1 of HIV?
- Asymptomatic
- Persistant generalised lymphadenopathy
- Normal activity
Stage 2 of HIV?
- Weight loss <10% of body weight
- Minor mucocutaneous manifestations (Seborrheic dermatitis, prurigo, fungal nail infections, recurrent oral ulcerations, angular chelitis)
- Herpes Zoster
- Recurrent Upper respiratory tract infections (Bacterial sinusitis)
- Normal activity
Which clinical stage can Seborrheic dermatitis first appear in HIV?
Minor mucocutaneous manifestations can appear in Stage 2
Which clinical stage can fungal nail infections first appear in HIV?
Minor mucocutaneous manifestations can appear in Stage 2
Which clinical stage can recurrent oral ulcerations first appear in HIV?
Minor mucocutaneous manifestations can appear in Stage 2
Which clinical stage can angular chelitis first appear in HIV?
Minor mucocutaneous manifestations can appear in Stage 2
Which clinical stage can Herpes Zoster first appear in HIV?
Stage 2
Which clinical stage can Bacterial sinusitis first appear in HIV?
Recurrent Upper respiratory tract infections can appear in Stage 2
Stage 3 of HIV?
- Weight loss >10% of body weight
- Unexplained chronic diarrhoea (>1 month)
- Unexplained prolonged fever (>1 month)
- Oral candidiasis
- Oral hairy leukoplakia
- Pulmonary TB
- Severe bacterial infections
- Bedridden, 50% of the day during the last month
Which clinical stage can is there weight loss <10% of body weight in HIV?
Stage 2
Which clinical stage can is there weight loss >10% of body weight in HIV?
Stage 3
Which clinical stage can is there chronic diarrhoea in HIV?
Stage 3
Which clinical stage can is there oral candidiasis in HIV?
Stage 3
Which clinical stage can is there oral hairy leukoplakia in HIV?
Stage 3
Which clinical stage can is there pulmonary TB in HIV?
Stage 3
Which clinical stage can is someone bed ridden for 50% of the time during a month in HIV?
Stage 3
Which clinical stage can is there chronic fever in HIV?
Stage 3
Which clinical stage can is there wasting syndrome in HIV?
Stage 4
Which clinical stage can is there Pneumocystic caring pneumonia in HIV?
Stage 4
Which clinical stage can is there toxoplasmosis of the brain in HIV?
Stage 4
Which clinical stage can is there CMV disease go an organ other than the liver, spleen or lymph nodes in HIV?
Stage 4
Which clinical stage can is there HSV mucocutaneous >1 month or visceral any duration in HIV?
Stage 4
Which clinical stage can is there progressive mulitfocal leukocephalopathy in HIV?
Stage 4
Which clinical stage can is there disseminated endemic mycosis in HIV?
Stage 4
Which clinical stage can is there candidiasis in the oesophagus, trachea, bronchus or lungs in HIV?
Stage 4
Which clinical stage can is there non-typhoid salmonella septicaemia in HIV?
Stage 4
Which clinical stage can is there extra pulmonary TB in HIV?
Stage 4
Which clinical stage can is there Kapoi’s sarcoma in HIV?
Stage 4
Which clinical stage can is there HIV encephalopathy, as defined by CDC b in HIV?
Stage 4
During stage 4 of HIV what is the performance scale?
Bedridden for <50% of the day during the last month
What is the CD4 count when thrush begins to occur in HIV?
<350 CD4
What is the CD4 count when skin changes begins to occur in HIV?
<350 CD4
What is the CD4 count when PCP begins to occur in HIV?
<200 CD4
What is the CD4 count when TB begins to occur in HIV?
<200 CD4
What is the CD4 count when cryptosporidiosis begins to occur in HIV?
<100 CD4
What is the CD4 count when Kaposis lymphoma begins to occur in HIV?
<200 CD4
What is the CD4 count when toxoplasmosis begins to occur in HIV?
<100 CD4
What is the CD4 count when cryptococcal meningitis begins to occur in HIV?
<100 CD4
How is HIV diagnosed?
4th generation ELISA/Western blot tests to look for antibodies to viral proteins
Often false negative in first 1-2 months of infection
Often false positive on new born babies born to infected mothers (anti-gp120 crosses the placenta)
How is AIDs diagnosed?
One of the following:
1) <200 CD4+ count
2) HIV + AIDs defining condition (Eg Pneumocystis pneumonia)
3) CD4+ Percentage <14%
Can you recover from an AIDs illness?
Yes virtually everyone with an AIDs can recover to HIV+ and then should be kept on antivirals
Which cancers are HIV patients particularly high risk of developing?
- Non-Hodgkins Lymphoma
- Cervical cancer
- Kaposi’s Sarcoma
What is primary HIV/seroconversion?
1) Approx 30-60% of patients with HIV get seroconversion illness, when HIV antibodies first develop
2) Abrupt onset 2-4 weeks post exposure, self-limiting 1-2 weeks
3) Symptoms are non-specific
Symptoms that may occur due to seroconversion illness in HIV?
- Flu-like illness
- Fever
- Malaise and lethargy
- Pharyngitis
- Lymphadenopathy
- Toxic exanthema
What is cART?
Combination antiretroviral therapy - At least 3 drugs from at least 2 groups
For antiretroviral therapy to work in HIV what does the adherence rate need to be?
90%
Where do different treatments act in HIV?
1) Fusion (Binding and entry):
- Attachment = Maraviroc
- Penetration = Enfuvirtide
2) Reverse transcription inhibitors:
- NRTIs
- NNRIs
3) Integration:
- Integrase inhibitors
4) Transcription
5) Assembly
6) Release and Proteases:
- Protease inhibitors
7) Maturation inhibitors
When should treatment be started in HIV?
- CD4 <350 cells/mm3 Should be encouraged
- CD4 <200 cells/mm3 needs to be started
- Pregnant woman - Start before third trimester
When should treatments be adjusted in HIV?
If there isn’t a adequate suppression of VL after 4-6 weeks of therapy
What is the life expectancy of someone diagnosed in their 20s with HIV and a CD4 count <100?
52 years old
What is the life expectancy of someone diagnosed in their 20s with HIV and a CD4 count 100-200?
62 years old
What is the life expectancy of someone diagnosed in their 20s with HIV and a CD4 count >200?
70+ years old
Why may treatments fail in HIV?
1) Incomplete suppression:
- Inadequate potency
- Inadequate drug levels
- Inadequate adherence
- Pre-existing resistance
2) Resistant quasispecies
Poor adherence is the main reason, this leads to viral mutation and resistance
What is a nucleoside?
Reverse transcriptase inhibitors
What are the negative side-effects of nucleosides?
- Marrow toxicity
- Neuropathy
- Lipodystrophy
What are non-nucleosides?
Reverse transcriptase inhibitors
What are the negative side-effects of non-nucleosides?
- Skin rashes
- Hypersensitivity
- Drug interactions
What are protease inhibitors?
Protease inhibitors act to inhibit the assembly of virions
What are the negative side-effects of proteases?
- Drug interactions
- Diarrhoea
- Lipodystrophy
- Hyperlipidaemia
- Hyperglycaemia
What are integrate inhibitors?
Inhibit HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
What are the negative side-effects of integrate inhibitors?
- Rashes
- Increase in creatine kinase
What is lipodystrophy?
Cushing like syndrome:
- Visceral abdominal fat
- Complete or partial loss of adipose tissue seen most on the limbs and face
How can we treat lipodystrophy?
1) Remove/change the causative drug
2) Cosmetic procedures:
- Facelift
- Liposuction
- Fillers
What are the main challenges in HIV care?
- Cerebrovascular disease
- Renal disease
- Ischaemic heart disease
- Diabetes mellitus
- Malignancy
- Cognitive impairment
- Osteoporosis
How can we prevent HIV?
- Behavioural changes
- Condoms
- Circumcision
- Treatment as prevention e.g. in pregnancy if VL is undetectable then there is low risk of transmission
- Pre-exposure prophylaxis (PrEP)
- Post-exposure prophylaxis for sexual exposure (PEPSE)
When should PEPSE be taken?
Post-exposure prophylaxis for sexual exposure (HIV) no later than 72 hours after exposure to the virus
Where is PEPSE available?
Post-exposure prophylaxis for sexual exposure (HIV) no later than 72 hours after exposure to the virus
It can be attained from a sexual health clinic or Accident and Emergency department
What is PEP?
Post-exposure prophylaxis following exposure to HIV.
It is a 4-week course of pills
Future of HIV care?
- Therapeutic vaccines
- Long-acting injectable drug treatments
- Cure - “Kick-kill” strategies
What is the actual name of AIDS?
Acquired immune deficiency syndrome
What happened in 1981 regarding HIV?
Increased number of cases of Kaposi’s Sarcoma and Pneumocystis carinii pneumonia within the gay community
What happened in mid-1982 regarding HIV?
It was realised that HIV was not only present in the gay community but also those who used heroin or blood products (Haemophiliacs)
When was the name AIDS adopted?
September of 1982
What was the first confirmed case of HIVin Europe?
A Norwegian sailor who had travelled to West Africa in 1961 and 1964 who developed gonorrhoea. Later lung infections and dementia in 1970s –> died 1975
His wife and 9 year old daughter died in 1977
Blood samples were taken from all three and HIV was confirmed in them in 1987
What is the source of HIV infection in humans?
A type of chimpanzee in Central Africa - It is believed that the chimpanzee version of HIV virus (simian immunodeficiency virus, or SIV) was transmitted and mutated into HIV when humans hunted and ate chimpanzee meat
What is simian immunodeficiency virus,?
The chimpanzee version of the HIV virus and believed to be the source of HIV in humans
What percentage of the world number of people with HIV is found in Sub-Saharan Africa ?
2/3rds
Incidence: Male
In Europe are males of female more likely to be HIV positive?
Male
In Sub-Saharan Africa are males of female more likely to be HIV positive?
Women
In the heterosexual community what is the most likely source of HIV in the UK?
From abroad
What are the distinct viruses in HIV?
1) HIV-1:
- Group M (Several more groups)
- Group N
- Group O
- Group P
2) HIV-2
Which form of HIV is more prevalent worldwide?
HIV-1 Group M
How does the HIV virus replicate?
Retroviruses replicate using reverse transcriptase
Which component of HIV virus allows mature virus progeny?
Protease enzymes
Which component of HIV virus facilitates the integration into the host cell DNA?
Integrase
A genome of retroviruses is made of what?
RNA
How many chain does each retrovirus have?
Two single chains of RNA
What is a group of retroviruses called?
Lentiviruses
What can be used to monitor the management of HIV?
- Viral load (VL)
- HIV resistance testing
- Avidity testing
- Subtype determination
- Tropism testing
- Drug levels
What has to occur before HIV can be detected?
Seroconversion –> Increase in Ab level
What is the bonus of 4th generation ELISA testing in HIV?
Allows detection of HIV antibody and antigen in HIV positive individuals >1 month after exposure
How do we test viral load?
HIV genome detection
What is a positive test for HIV RNA?
range from 40 to >10 million genome copies/ml blood
What is viral load used for in HIV?
1) Monitor the effectiveness of HIV treatment
2) Diagnosis in presence of maternal antibody
What is HIV resistance testing?
Sequencing of the polymerase and protease genes.
This allows identification of specific mutations that confer resistance to antiretroviral drugs
What is tropism testing used for in HIV?
Which co-receptor does the virus use to enter CD4 cells, required before using a CCR5 antagonist
Why would we test drug levels in HIV?
Compliance
Will I need to tell my work?
If you are not required you to have an HIV test as part of your work then no
If you work in healthcare and contract HIV what should be followed?
You need to avoid exposure-prone procedures (EPPs)
When may your work find out that you are HIV positive?
- If testing is required e.g. for a work visa abroad
What happens to viral load and CD4 count following treatment in HIV?
- Viral load decrease
- CD4 increases
What is the risk of BBV to health care workers?
Penetrating exposure (Needle-stick):
- HBV up to 30% (1:3)
- HCV -3% (1:30)
- HIV 0.3% (1:300)
Mucocutaneous exposure (Blood or other body fluid splashes into eyes, nose or mouth or broken skin: - HIV <0.1% (1:1000)
Which body fluids are high risk of BBV transmission?
- Blood
- Cerebrospinal fluid
- Pleural, peritoneal, pericardial fluid
- Amniotic fluid
- Breast milk
- Vaginal secretions, semen
- Synovial fluid
- Unfixed tissue and organs
- Saliva
- Exudate/tissue fluid from burns or skin lesions
What should be done after exposure to blood or body fluids?
1) Wash off splashes on skin with soap and running water
2) Encourage bleeding if the skin has been broken
3) Wash out splashes in the eye, nose or mouth
4) REPORT to senior manager or doctor and OHS
After exposure to blood or body fluids risk is assessed on the basis of what?
- The source of contamination
- The extent of injury and type of sharp (if any) causing it
- The likelihood of B/C/HIV in the source
- The vaccination history
In 1995, what was used post exposure to HIV?
Zidovudine, which reduced the risk of HIV seroconversion after exposure by 79% if given promptly
In 1997, what was used post exposure to HIV?
Combination post-exposure prophylaxis (PEP) recommended ASAP, preferably within ONE hour (but still consider if delay up to ~ 72 hours)
In 2008, what was used post exposure to HIV?
Truvada & Kaletra, within 48-72 hrs of exposure, continued for 28 days
What should occur following exposure to HBV?
HB vaccine administered +/- Immunoglobulin
Source the patient and test them
What should occur following exposure to HCV?
There is:
- No known vaccine,
- No immunoglobulin available for PEP
- No anti-viral therapy licenced for PEP
However early treatment can still decrease the risk of chronic infection
Source the patient and test them
Ways to avoid exposure to BBV in the health care setting?
- Apply good basic hygiene practices with regular hand washing.
- Cover existing wounds or skin lesions with waterproof dressings.
- Take simple protective measures 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 wherever possible.
- Use a safe procedure for handling and disposal of sharps.
8 Clear up spillage of blood or body fluids promptly and disinfect surfaces. - Follow procedures for the safe disposal of contaminated waste.