HIV Flashcards
What diseases can the HIV virus cause?
- Acquired Immunodeficiency Syndrome (AIDS)
- Opportunistic Infections
- AIDS-related cancers
People with treated HIV have a “near normal” life expectancy. TRUE/FALSE?
TRUE
HIV infection is preventable. TRUE/FALSE?
TRUE
What are the two main types of HIV virus?
- HIV-2 originated in West Africa
- Less virulent
- HIV-1 originated in Central/West African chimpanzees
- HIV-1 group M responsible for global pandemic starting in 1981
What is CD4 in relation to HIV?
CD4 (Cluster of Differentiation)
- glycoprotein receptor found on the surface of cells
- target site for HIV
What types of cells have CD4 receptors on their surface and therefore are susceptible to HIV infection?
- T helper lymphocytes (“CD4+ cells”)
- Dentritic cells
- Macrophages
- Microglial cells
What do CD4+ T lymphocytes do?
Induce adaptive immune response: => Recognition of MHC Class II antigen-presenting cell => Activation of B-cells => Activation of cytotoxic T-cells (CD8) => Cytokine release
How does HIV change the immune response?
- Reduced circulating CD4 cells
- Reduced proliferation of CD4 cells
- Reduced CD8 T cell activation
- Dysregulated cytokines
- Reduced affinity of Ab produced
- Chronic Immune Activation
HIV effect on the immune response makes people more susceptible to what types of infection?
- Viral infections
- Fungal infections
- Mycobacterial infections
- Infection-induced cancers
What are the normal parameters for CD4 T cells?
500-1600 cells/mm3
What CD4 levels would indicate the potential for opportunistic infection?
<200
What is meant by opportunistic infection?
Infection caused by a pathogen that could collonise and not cause disease in a healthy individual
When does replication occur during HIV infection?
- Rapid replication in very early and very late infection
- New generation every 6-12 hours
What is the average time to death if no treatment is given in HIV infection?
9-11 years
What happens to the CD4 count during and after acute HIV infection?
CD4 count goes down in initial acute infection then comes back up before steady decline
Explain how the virus gets from initial infection to dissemination
Infection of mucosal CD4 cell
Transport to regional lymph nodes
Infection established within 3 days of entry
Dissemination of virus
What percentage of Primary HIV infections present symptomatically and within how long?
80%
onset usually within 2-4 weeks
What symptoms may appear with disseminated HIV?
- Fever
- Rash
- Myalgia
- Pharyngitis
- Headache/aseptic meningitis
What pneumonia do HIV patients often get and what CD4 count usually causes this?
Pneumocystis jiroveci
CD4 threshold: <200
WHat are the symptoms and signs of pneumocystis pneumonia in patients with HIV?
insidious onset
SOB
Dry cough
Signs: exercise desaturation - get tachy and sats decrease rapidly after 5 mins of exercise
A CXR for pneumocystis pneumonia in HIV may be normal. Why is this?
Diffuse infiltrates => no clear sign of lobar consolidation
What tests are used to diagnose pnuemocystis pneumonia?
Bronchoalveolar Lavage and immunofluorescence +/- PCR
What treatment is used for pneumocystis jirovecii?
- Treatment: high dose co-trimoxazole (+/- steroid)
- Prophylaxis: low dose co-trimoxazole
What features of TB are more common in patients with positive HIV infection?
- Symptomatic primary infection
- Reactivation of latent TB
- Lymphadenopathies
- Extrapulmonary TB
- drug resistant TB
- Immune reconstitution syndrome
Cerebral toxoplasmosis is caused by what microorganism and at what CD4 count?
Cerebral toxoplasmosis
Toxoplasma gondii
CD4 threshold: <150
How does cerebral toxoplasmosis appear on neuro-imaging?
Multiple cerebral abscess
What symptoms and signs may indicate a toxoplasmosis infection
Headache Fever Focal neurology Seizures Reduced consciousness Raised intracranial pressure
What CD4 count causes HIV patients to be susceptible to CMV?
CD4 threshold: <50
What does CMV infection cause and how do patients present?
Causes: retinitis, colitis, oesophagitis
Presentation:
- Reduced visual acuity
- Floaters
- Abdo pain, diarrhoea, PR bleeding
What skin infections may indicate that a patient may have HIV?
Herpes Zoster
- If rash appears in Multiple dermatomes
- If frequently recurrent
Herpes Simplex
- If extensive
- If Aciclovir resistant
Human Papilloma Virus
- Extensive
- Dysplastic
HIV can cause neurocognitive impairment. At what CD4 count does this present and what symptoms can occur?
No CD4 threshold - can happen at any level of immunosuppression
Causes
- Reduced short term memory
- potentially motor dysfunction also
What is Progressive multifocal leukoencephalopathy, and what virus causes this?
Caused by: JC virus
Affects frontal lobe of brain =>
- Rapidly progressing
- Focal neurology
- Confusion
- Personality change
What CD4 threshold is required for JC virus infection?
CD4 threshold: <100
What other neurological presentations can be due to HIV?
- polyneuropathy
- Mononeuritis multiplex
- Aseptic meningitis
- Guillan-Barre syndrome
- Viral meningitis (CMV, HSV)
- Neurosyphilis
Why do patients with HIV sometimes present with muscle wasting or “slims disease”?
Virus is using up energy that patient would usually use to put on weight
Human herpes virus 8 (HHV8) causes what AIDS related cancer?
Kaposi’s sarcoma (vascular tumour)
Causes lesions that are:
- Cutaneous
- Mucosal
- Visceral – pulmonary, GI
How is Kaposi’s Sarcoma treated?
if just cutaneous lesions => normal HIV anti-retrovirals
If visceral lesions then may need systemic chemo
What organism can cause Non-hodgkins lymphoma in HIV patients?
EBV
How do HIV patients with non-hodgkins lymphoma usually present?
- Present more advanced
- Bone marrow involvement
- Extranodal disease
- ↑ CNS involvement
HOw is Non-Hodgkins lymphoma in HIV treated?
Treat cancer as if patient was HIV negative BUT add anti-retrovirals
What conditions may patients with HIV develop that they still deem as “asymptomatic” HIV?
Minor conditions where they may have needed to seek medical advice E.g.
- Thrush
- Seborrhoeic dermatitis
- Diarrhoea
- Fatigue
- Worsening psoriasis (due to CD8)
- Lymphadenopathy
- STIs/ BBV
How can HIV manifest haematologically?
Anaemia
Thrombocytopenia
What factors increase the risk of HIV transmission during sex?
Anoreceptive sex
Trauma
Genital ulceration
Concurrent STI
HOw can HIV be transmitted “parenterally”?
- Injection drug use (sharing needles)
- Infected blood products
- Iatrogenic
HOw can mother to child transmission of HIV take place?
- In utero/trans-placental
- Delivery
- Breast-feeding
Where are the current pandemics of HIV taking place, and in what parts of the world are epidemics rising?
PANDEMICS
Sub Saharan Africa
Caribbean
South East Asia
Rising EPIDEMICS
Russia, Eastern Europe
What is the prevalence of HIV in the UK?
1.6/1000
What groups are at higher risk of HIV?
- Men who have sex with men (MSM)
- certain areas (e.g. London)
- Ethnicity => Black men and women
- PWIDs
What groups are usually diagnosed with HIV late?
Women
Older patients
Heterosexual patients (especially men, as women are often picked up on antenatal screening)
Who should be tested for HIV?
- Universal testing in high prevalence areas
- Opt-out testing (patient can decline)
- Screening of high risk groups
- Testing in the presence of “clinical indicators”
What high risk groups should be screened routinely for HIV?
- Men who have sex with men
- Female partners of bisexual men
- People who inject drugs
- Partners of people living with HIV
In what high risk areas should patients routinely be screened for HIV?
- Adults OR children from endemic areas (e.g. Africa)
- Sexual partners from endemic areas
- History of iatrogenic exposure in an endemic area
How can you normalise the explanation of an HIV test to a patient?
- To check your immune system is working okay
- Benefits of testing are:
- Improve long term health
- Protect partner(s)
If a patient is deemed to NOT have capacity, do you perform an HIV test?
- Only test if in patient’s best interest
- Consent from relative not required
- If safe, wait until patient regains capacity
- Obtain support from HIV team if required
What markers are used by labs to detect HIV infection?
- p24 protein
- Viral load and antibodies can also be used but longer window period (3 months)
What is the window period for 4th generation HIV testing?
14-28 days
Rapid HIV tests done at a patients bedside consist of what?
Fingerprick blood specimen or saliva
Results within 20-30 minutes
3rd generation (Ab only) or 4th generation (Ab/Ag)
What are the advantages/ disadvantages of rapid HIV testing?
ADV: Simple No lab required No venepuncture required Good sensitivity
DISADV:
Expensive ~£10
If in low prevalence area - positive prediction not high
Can’t be relied on in early infection
What should be looked out for on physical examination of a patient who has tested HIV positive?
Kaposi’s Sarcoma (cutaneous lesions)
Thrush
Symptoms of pneumonia
STIs
Some HIV viruses can be resistant. TRUE/FALSE?
TRUE
What proteins are involved in HIV replication in CD4 cells and are therefore targets for treatment?
Reverse transcriptase (replicates virus)
Integrase (integrates HIV into genome)
Protease (cleaving)
CCR5 (co-receptor when HIV binds to CD4)
What is HAART?
Highly active anti-retroviral therapy
What is involved in modern HAART?
combination of 3 drugs
from at least 2 drug classes (to which the virus is susceptible)
What are the 3 main aims of HAART?
- Reduce viral load to undetectable
- Keep viral load down
- Let immune system recover
- Reduce morbidity and mortality
HAART is often available in a single tablet coformulation. What does this mean?
3 drugs in one tablet (spanning at least 2 drug classes)
=> patient only needs to take ONE tablet once a day
How is drug resistance prevented?
Adherence/ compliance to medication
- if patient stops drugs, then the half life means at least one drug will still be in the patients system when the virus begins to replicate again
- virus will then become resistant to that drug
What symptoms/conditions would indicate HAART toxicity?
- GI side-effects (caused by protease inhibitors)
- Skin: rash, hypersensitivity, Stevens-Johnsons
- Psych: mood, psychosis
- Renal toxicity: proximal renal tubulopathies
- Bone: osteomalacia
- CVS: increased MI risk
- Haematology: anaemia
Why may some HAART require pharmacological boosting?
require pharmacological boosting with potent liver enzyme inhibitors
=> prevent breakdown of the drug
What co-infections are difficult to treat with HIV?
Hepatitis C and TB = drug interactions with HIV
Hepatitis B = same treatment as HIV!
What other comorbidities often need managed in older HIV patients?
Non-alcoholic fatty liver disease Cognitive decline Renal Impairment Bone Health Cancers Cholesterol (as some HIV drugs increase this)
How are the complications of HIV being prevented?
- Educating patients on CVS risk (exercise etc)
- Smoking cessation
- STI screening
- Vaccines (Hep A/B, Flu, HPV)
- Harm reduction (using condoms, needle exchange etc)
What are the different strategies of Partner Notification?
Partner referral (patient tells partner themself)
Provider referral (Sexual health clinic informs partner whilst other person remains ananoymous)
Conditional referral (patient attempts to tell partner, but clinic will tell them if longer than an agreed period of time)
Why do patients struggle with partner notification?
Fear of:
- Rejection
- Isolation
- Violence
- Stigma
How do we prevent sexual transmission of HIV?
- Condom use
- compliance with HIV treatment
- STI screening and treatment
- Sero-adaptive sexual behaviours
- e.g. more likely to transmit HIV if positive person is the insertive partner in MSM
- Post-exposure prophylaxis (PEP)
- Pre-exposure prophylaxis (PrEP)
Couples where one member is HIV positive must conceive via intra-uterine insemination or ICSI. TRUE/FALSE?
FALSE - this was old method of conceiving in couples where one member was HIV positive
NOW these couples can conceive naturally
How is mother to child transmission of HIV prevented?
- HAART during pregnancy
- Vaginal delivery if undetected viral load
- Caesarean section if detected viral load
- 4 weeks of PEP for neonate
- Exclusive formula feeding (this may change in future)
What methods of preventing HIV transmission have had an impact?
- Needle exchange
- Testing and treatment for STIs
- Condom programmes
- Behaviour change interventions
- Circumcision
- PrEP (high risk individuals)/PEP
- Treatment as prevention
Why is circumcision considered an HIV prevention method?
Many CD4 cells sit in foreskin => by removing this it decreases the number of cells for HIV to infect
ALSO - when circumcised, the glans penis becomes keratinised to deal with trauma => decreased trauma = decreased number of HIV transmissions
What was the UN HIV/AIDS target for 2020?
90-90-90
=> 90% of people with HIV are aware of their status
=> 90% of those who know they are HIV positive are on treatment
=> 90% of those on treatment for HIV have an undetectable viral load
What would indicate that a patient is at high risk of HIV and therefore should be given PrEP?
- HIV+ partner with detectable viral load
- MSM or transwoman
- OR other high risk reason
What criteria must patients meet to be eligible for PrEP?
Aged ≥ 16 HIV negative Can commit to 3 monthly follow-up Willing to stop if eligibility criteria no longer apply Resident in Scotland
