HIV Flashcards
What is HIV ?
It is a virus which when left untreated causes acquired immunodeficiency syndrome (AIDS)
What is the life-expectancy of someone with HIV?
Someone with treated HIV will have a near normal life expectancy because AIDS is prevented
What is the most common cause of HIV related morbidity & mortality ?
- Late diagnosis - 13% of those in the UK are undiagnosed
- This means there is time for HIV-related complications to develop
What are the 3 largest groups of people living with HIV in the UK?
- MSM
- Heterosexual people from sub-sahran africa
- PWID
What are the most common places in the world affected by HIV ?
- Sub-saharan africa
- Caribbean
- South-east asia
What type of virus is HIV and what are the main sub-types
- It is a retrovirus
- 2 types - HIV-1 (most common globally) & HIV-2 (largely confined to africa)
What is the target sites of HIV virus in the body and what is the relevence of this
CD4+ receptors are the target site
What is CD4+ and where is it found ?
It is a glycoprotein found on the surfaces mainly of the following cells:
- T-helper lymphocytes
- Dendritic cells
- Macrophages
- Microglial cells (immune cells in the CNS)
What is the function of CD4+ Th lymphocytes ?
CD4+ Th lymphocytes are essential for induction of the adaptive immune response, they recognise MHC2 antigen presenting cells & then activate B cells (these turn into antibodies), macrophaes, & killer T cells. They also release cytokines which tell macrophages & other lymphocytes etc to come over & help
Describe the stages of HIV infection and development into AIDS
- Initial exposure - infection of mucosal CD4+ cell (dendiritic cell), virus is then transported by these cells to regional lymph nodes, infection becomes established within 3 days of exposure (short window to cure patient)
- Primary infection phase - this is the first 6 months following exposure
- Asymptomatic phase - this can last ≥ 10years
- Constitutional symptoms develop just before AIDS
- Development of AIDS
- Death - takes 9-11 years without treatment
What effect does HIV infection have on the immune response ?
- Sequestration of cells in lymphoid tissues ==> resulting in reduced circulating CD4+ cells
- Reduced proliferation of CD4+ cells
- Reduction CD8+ (cytotoxic) T cell activation - due to dysregulated expression of cytokines (cytokines needed to activate them recall function of CD4+ Th lymphocyte)
- Reduction in B cells becoming antibodies
- Chronic Immune Activation
These all lead to incresed susceptibility to infection & infection-induced cancers
What is the normal parameters of CD4+ Th cells and what counts shoud you be worried about getting opportunistic infections ?
- Normal: 500-1600 cells/mm3
- Risk of opportunistic infections when: <200 cells/mm3
What are the different ways in which HIV infection can be transmitted ?
- Sexual intercourse (vaginal & anal)
- Mother to child (in utero, during delivery & during breastfeeding)
- PWID
- Infected blood products
What are the clinical features of primary HIV infection and when do symptoms/signs usually occur after exposure ?
Symptoms usually occur 2-4 weeks after exposure and present with a combination of:
- Fever
- Rash (maculopapular)
- Myalgia
- Pharyngitis
- Headache/aseptic meningitis
What is the risk of onward transmission of HIV during the primary infection stage ?
Very high - during this period there is uncontrolled viral replication (high HIV levels circulating)
During the primary infection stage of HIV what is happening to the CD4+ count ?
It is decreasing whilst the HIV levels are increasing
What clinical features during the asymptomatic stage of HIV infection may someone have ?
Persistent lymphadenopathy
Alos multiple niggly things which are easily overlooked:
- Mucosal candidiasis
- Sebhorrhoeic dermatitis
- Diarrhoea
- Fatigue
- Worsening psoriasis
- Parititis
- STI’s
- Hep B or C
During the asymptomatic phase of HIV infection what is happening to the CD4+ counts and HIV viral load ?
- CD4+ counts still decreasing
- HIV viral load increasing
Following the asymptomatic phase patients develop aids related complex - symptomatic HIV infection, what are the symptoms which patients presnet with?
Constitutional symptoms:
- Fever
- Night sweats
- Diarrhoea decreased weight
- Minor opportunisitic infections e.g. oral candida, hairy leukoplakia, herpes zoster, recurrent HSV, regular infections
What is AIDS charactersied by ?
- Being HIV positive & having an indicator disease i.e. opportunistic infection
- CD4+ count is also usually < 200 cells/mm3
Define what an opportunisitic infection is
This is an infection caused by a pathogen that does not normally produce disease in a healthy individual
What is by far the most common opportunisitc infection seen in HIV?
Pneumocystis pneumonia
What is the causative organism of Pneumocystis pneumonia ?
Pneumocystis jiroveci
Under what CD4+ count does a patient become susceptable to Pneumocystis pneumonia infection?
< 200
What are the signs/symptoms of Pneumocystis pneumonia infection?
- SOB & dry cough over a number of weeks
- Excercise desaturation - O2 sats <88% during exercise
How is Pneumocystis pneumonia diagnosed ?
BAL & Sputum immunofluorescence (gained via cough or broncoscopy) +/- PCR
What is the treatment of high Pneumocystis pneumonia infection ?
High dose co-trimoxazole +/- steroid (prednisolone) if severe hypoxia
What prophylatic treatment can be given to prevent further attacks of Pneumocystis pneumonia and when is this given ?
If CD4+ count < 200 then given low dose co-trimoxazole after 1st attack until CD4+ count is > 200
If a HIV +ve patient has cough, fever, night sweats or weight loss, what do they have until proven otherwise ?
TB
How is active TB diagnosed ?
CXR + multiple sputum samples for TB microscopy & culture
What is latnet TB infection ?
This is where you’ve been infected with TB but do not have any symptoms
What investigations should be done for someone at risk of having latent TB i.e. those who have been in close contact of a person with pulmonary or laryngeal TB ?
- 1st line = mantoux test if +ve then
- 2nd line = assess for active TB
What is the main CNS pathogen affecting AIDS patients ?
Cerebral toxoplasmosis
What is the causative organism of cerebral toxoplasmosis ?
Toxoplasma gondii
What are the signs/symptoms of cerebral toxoplasmosis ?
- Headache
- Fever
- Focal neurology
- Seizures
- Reduced consciousness
- Raised ICP
What is the characteristic appearance seen on CT scan of cerebral toxoplasmosis ?
Multiple cerebral abcesses
At what CD4+ count should you be worried about CMV infection ?
<50
How can CMV infection present in HIV patients ?
- Reduced visual acuity
- Floaters
- Abdo pain, diarrhoea, PR bleeding
Because it can cause retinitis, colitis and oesophagitis
Why is opthalmic screening required for all individuals with a CD4+ count <50 ?
This is because CMV infection can lead to blindness
Go over some of the skin infections which might make you think someone has HIV
- Herpes Zoster - Multidermatomal, Recurrent
- Herpes Simplex - Extensive, Hypertrophic, Aciclovir resistant not responding to tx
- Human papilloma virus - Extensive, Recalcitrant, Dysplastic
- Weird/wonderful infections - Penicilliosis, Histoplasmosis
When HIV becomes disseminated throughout the body it also invades the brain & replicates causing inflammation & damage resulting in cognitive behavioural and motor difficulties, what is this condition called and what HIV virus causes this ?
Known as HIV-associated neurocognitive impairment caused by HIV-1
What is the CD4+ threshold where HIV-associated neurocognitive impairment occurs ?
Any CD4+ count - its prevelence increasing with increasing immunosuppression (lower counts)
What are the presenting features of HIV-associated neurocognitive impairment ?
Reduced short term memory +/- motor dysfunction (dementia & encephalopathy symptoms as these are the neurocognitive conditions essentially being caused by the HIV)
What is progressive multifocal leukoencephalopathy ?
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal).
What CD4+ counts should you worry about progressive multifocal leukoencephalopathy development ?
<100
What is the causative organism of progressive multifocal leukoencephalopathy ?
JC virus
What are the presenting features of progressive multifocal leukoencephalopathy ?
- Rapidly progressing
- Focal neurology
- Confusion
- Personality change
List some of the other neurological manifestations of HIV besides PML and HIV-associated neurocognitive impairment
- Distal sensory polyneuropathy
- Mononeuritis multiplex
- Vacuolar myelopathy
- Aseptic meningitis
- Guillan-Barre syndrome
- Viral meningitis (CMV, HSV)
- Cryptococcal meningitis
- Neurosyphilis
If a patient presents with meningitis and you cannot find the cause what may you consider testing for ?
HIV
What is HIV associated wasting and the potential causes of it ?
It is weight loss of at least 10%
Has multiple aetiologies:
- Metabolic (chronic immune activation) ==> increased resting energy ependiture
- Anorexia (multifactorial e.g. painful oral, oesophageal complications)
- Malabsorption/diarrhoea
- Hypogonadism (decreased testosterone ==> decreased muscle mass etc)
What are the 3 main AIDS related cancers ?
- Kaposis sarcoma
- Non-hodgkins lymphoma
- Cervical cancer
Are kaposis sarcomas common in HIV patients now ?
They are much less common now, but did affect upto 40% pre-ART era
What is the causative organism of kaposis sarcoma ?
Human herpesvirus 8
What is the CD4+ count threshold for risk of development of kaposis sarcoma ?
Any, the incidence increases with increased immunosuppression
Describe the presenting features of a kaposis sarcoma
- Cutaneous: Usually appears as spots on the skin (lesions) esp on the legs and face, which may be purple, red or brown (can appear anywhere)
- Mucosal: It can also develop on mucosal surfaces affecting the mouth & throat
- Visceral: The pulmonary (causing blockage or SOB) and GI tracts (causing abdo pain & diarrhoea) may also be affected
Note - you can get other features of cancer e.g. weight loss, haemoptysis, blood in stool, fatigue, anaemia
What is the treatment of kaposis sarcoma ?
- Optimise HAART +/- interferon-alpha
- May need topical retinoids, cryotherapy or radiotherapy for skin lesions
- Chemo may also be needed
What is non-hodgkins lymphoma ?
This is a cancer which starts in lymphocytes (mainly B-cell lymphocytes)
Infection with what is a risk factor for future non-hodgkins lymhoma development ?
EBV
What is the CD4+ threshold for risk of non-hodgkins lymphoma development ?
Any, increases incidence with increasing immunosupression
What are the presenting features of non-hodkins lymphoma ?
- Lymphadenopathy
- Fever
- Night sweats
- Fatigue, easy bruising, frequent infections
If affecting the abdomen - swelling or pain in abdo, loss of apetite
If affecting the chest - coughing, SOB, chest pain
If affecting the brain - headache, trouble thinking, focal neurology, personality change, seizures
If affecting the skin - appears as itchy red or purple bumps/lumps under the skin
How is non-hodkins lymphoma diagnosed ?
Refer to haem - bloods, marrow & node biopsy
What are the causative infections which greatly increase the risk of cervical cancer ?
HPV 16&18
What should be offered to all patients with complicated HPV disease i.e:
- Resistant/difficult to treat warts
- High grade CIN
HIV testing
What haematological manifestations may HIV patients present with ?
- Anaemia - affects upto 90%
- Thrombocytopenia (low platelets)
What should patients with thombocytopenia be tested for ?
HIV
What are the targerts for anti-retroviral drugs used in HIV treatment ?
- Reverse transcriptase
- Integrase
- Protease
- Entry - Fusion, CCR5 receptor
- Maturation
Why was mono&dual anti-retroviral therapy ineffective in HIV treatment ?
Because HIV is very good at developing resistance
What is used to treat HIV and what is it
HAART therapy
This is a combination of ≥ 3 drugs from at least 2 classes to which the virus is susceptible
What is the common intital HAART regime ?
2 NRTI’s + either a protease inhibitor or a non-NRTI
List all the classes of anti-retroviral drug classes which can be used in HIV treatment
- NRTI’s - abacavir, zidovudine, tenofovir,
- Protease inhibitors - atazanavir, lopinavir
- Integrease inhibitors
- Non-NRTI’s - nevirapine, efavirenz
- CCR5 antagnosits - maraviroc
State which of the following side effects are caused by which anti-retroviral drug/drug class:
- GI side-effects
- Skin: rash, hypersensitivity, Stevens-Johnsons
- CNS side-effects: mood, psychosis
- Renal toxicity: proximal renal tubulopathies
- Bone: osteomalacia
- CVS: increased MI risk
- Haematology: anaemia
- GI: transaminitis, fulminant hepatitis
- GI side-effects (protease inhibitors)
- Skin: rash, hypersensitivity, Stevens-Johnsons (abacavir, nevirapine)
- CNS side-effects: mood, psychosis (efavirenz)
- Renal toxicity: proximal renal tubulopathies (tenofovir, atazanavir)
- Bone: osteomalacia (tenofovir)
- CVS: increased MI risk (abacavir, lopinavir, maraviroc)
- Haematology: anaemia (zidovudine)
- GI: transaminitis, fulminant hepatitis (nevirapine, most others)
How soon should partner notification be completed by i.e. telling someone they could have transmitted onto
Ideally within 3 months - but may be persued further if there is clear timelines
Due you have a duty of care to a known 3rd party in terms of partner notification?
Yes
What steps should be taken to prevent onward HIV sexual transmission ?
- Condom use
- HIV treatment
- STI screening and treatment
- Sero-adaptive sexual behaviours
- Disclosure
- Post-exposure prophylaxis (PEP)
- Pre-exposure prophylaxis (PREP)
Is there any risk of onward HIV transmission from casual/household contact?
No
For couples where one of them is HIV +ve what can be done to prevent onward transmission when trying to concieve ?
HIV+ male, HIV- female:
- Treatment as Prevention
- PreP in female partner
HIV+ female, HIV- male:
- ? Self-insemination
- Treatment as Prevention
- PreP in male partner
If whoever is infected have a viral load which is undetectable for > 6 months then the risk is minuscule of transmitting the virus
How is mother to child onward HIv transmission prevented during and after pregnancy ?
- HAART during pregnancy
- Vaginal delivery if undetected viral load
- Caesarean section if detected viral load
- 4/52 PEP for neonate
- Exclusive formula feeding is the best way to feed
