HIV Flashcards

(102 cards)

1
Q

What is the mechanism of action of nucleoside reverse transcriptase inhibitors?

A

These mimic the structure of nucleosides and act by competitive inhibition of reverse transcriptase. The bind to the active site of reverse transcriptase and are added to the growing DNA sequence but cause chain termination due to an azido group at the 3’ terminal.

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2
Q

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?

A

These bind to a site on the reverse transcriptase enzyme which is distant from the active site. This causes a change in conformation of the active site and thus inhibits the enzyme’s action.

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3
Q

List some key side effects of nucleoside reverse transcriptase inhibitors (NRTIs)

A
Peripheral neuropathy
Myopathy
Pancreatitis
Hepatis steatosis
Lactic acidosis
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4
Q

List some key side effects of non-nucleoside reverse transcriptase inhibitors

A

Rash
Hepatitis
Vivid dreams
Insomnia

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5
Q

What is the mechanism of action of protease inhibitors?

A

The HIV protease enzyme is responsible for post-translational modification of viral proteins e.g. cutting up so they can be packaged into new viruses for budding from the host cell and spreading. Inhibition means that immature protein is produced and this cannot infect other host cells.

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6
Q

Which key protease inhibitor can be used in conjunction with other protease inhibitors to enhance their effect? Why?

A

Ritonavir - It is a cytochrome p-450 inhibitor…most protease inhibitors are metabolised by cytochrome p-450 so ritonavir inhibits their metabolism thus lengthening the time they are effective

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7
Q

List some side effects of protease inhibitors

A
Insulin resistance
Hyperlipidaemia
Lipid deposition at trunk
Increased cardiovascular risk
Nephrolithiasis
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8
Q

What is the mechanism of action of integrase inhibitors?

A

Prevents viral DNA from being incorporated into the host genome (a process usually catalysed by integrase enzyme)

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9
Q

What is CCR5?

A

This is a chemokine receptor on the host cell surface which acts as a co-receptor for enabling entry of HIV into the host cell. It can be inhibited by CCR5 antagonists e.g. Maraviroc

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10
Q

What is gp-120?

A

This is a protein on the HIV surface which binds to CD4 on the host cell to enable entry.

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11
Q

What is the mechanism of action of a ‘fusion inhibitor’?

A

Binds to gp-41 on the HIV virus which then prevents binding of gp-120 to CD4, thus preventing the HIV attaching to the host cell

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12
Q

List the 6 different types of antiretroviral therapies used in the UK

A

Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Integrase inhibitors
Protease inhibitors
Fusion inhibitors
CCR5 receptor antagonists

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13
Q

Which oncogenic virus is responsible for causing Kaposi’s Sarcoma, and how is the virus transmitted?

A

Human Herpesvirus 8 (HH8) - transmitted vertically or horizontally

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14
Q

Which organ systems are mostly affected by Kaposi’s Sarcoma?

A
Skin
Mouth
Lung
Stomach
Eyes
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15
Q

How might a patient with primary cerebral lymphoma present?

A

Headaches
Focal neurology
Onset over 2-8 weeks
No fever

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16
Q

What might brain imaging show in primary cerebral lymphoma?

A

Multiple, ring enhancing lesions which are periventricular
Mass effect
Cerebal oedema

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17
Q

What is the difference between lesions on brain imaging seen in toxoplasmosis Vs. primary cerebral oedema

A

The location of lesions tends to indicate the cause:
Toxoplasmosis = Basal ganglia
Primary cerebral oedema = Periventricular

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18
Q

List some common malignancies associated with increased risk in HIV

A

Lymphoma - particularly Non-Hodgkin’s (systemic NHL and primary cerebral lymphoma)
Cervical
Anal
Castleman’s Disease

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19
Q

What is Castleman’s Disease?

A

Lymphoproliferative disorder associated with Kaposi’s Sarcoma herpesvirus (HHV-8). Patients present with fever, lymphadenopathy, hepatosplenomegaly and systemic symptoms.

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20
Q

What is the treatment for pulmonary cryptococcal infection in an HIV+ patient?

A

Fluconazole or, if more severe, liposomal amphoteracin and flucytosine

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21
Q

True / False - About 5% of new TB cases per year are attributed to HIV

A

False - About 12% of new TB cases each year are attributable to HIV infection

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22
Q

Why is sputum culture less useful for diagnosing TB infection in an HIV positive patient?

A

HIV positive individuals have a higher rate of extra-pulmonary TB so diagnosis would be useless in these cases.

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23
Q

Why may rifampicin be inappropriate for the treatment of TB in an HIV positive individual?

A

Rifampicin is an inducer of cytochrome p-450 enzymes and so has shown significant interaction with some HIV antiretroviral drugs. Sub therapeutic antiretroviral therapy will cause failure of HIV suppression and drug resistance so it’s important to check whether use of rifampicin is appropriate.

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24
Q

List 10 infections which might affect the eye in HIV

A
Cytomegalovirus
Herpes simplex virus
Varicella zoster virus
Toxoplasmosis
Tuberculosis
Chlamydia
Infective choroiditis
Gonorrhoea
Cryptococcus
Syphilis
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25
What is the most common opportunistic infection of the eye which affects HIV patients?
CMV retinitis
26
What is the treatment for CMV retinitis?
Intraocular ganciclovir Systemic treatment also required to prevent spread - Valganciclovir PO, or ganciclovir IV
27
What complication can occur months after a resolved case of CMV retinitis?
Retinal detachment - The large the extent of retinal involvement during infection, the greater the risk of detachment.
28
What are the two main problems associated with HSV infection of the eye in HIV?
HSV keratitis | HSV retinitis
29
Truw / False - HSV retinitis can occur at a higher CD4 count than CMV retinitis
True - HIV+ patients are prone to HSV retinitis even at fairly reasonable CD4 counts.
30
Which imaging scan is important to carry out in toxoplasmosis infection affecting the eye?
Important to do cerebral imaging due to the common association with toxoplasmosis infection of the CNS
31
Argyll Robertson pupils are a sign of which infection affecting the eye in HIV? What are they?
Syphilis (in particular, tertiary). They are miotic pupils where there is no pupillary response to light, but constriction is present on accommodation.
32
What is the typical presentation of gonorrhoea affecting the eye in HIV?
Acute, purulent conjunctivitis
33
How does a cryptococcal infection affect the eye in HIV?
Cryptococcal meningitis can cause swelling of the optic disc and atrophy if untreated
34
In what way can malignant processes affect the eye in HIV (list 3 pathologies)?
Kaposi's sarcoma Lymphoma Squamous cell carcinoma of the conjunctiva
35
List 9 syndromes which may be neurological presentations of HIV at seroconversion
``` Aseptic meningitis Meningoencephalitis Transverse myelitis Acute disseminated encephalomyelitis (ADEM) Cauda equina syndrome Acute demyelinating polyradiculoneuropathy (Guillian-Barre Syndrome) Brachial neuritis Mononeuritis multiplex (vasculitis) Acute polymyositis ```
36
Which nerve palsy is particularly common in the asymptomatic phase of HIV infection?
VIIth nerve palsy
37
What is the most common organism to cause meningitis in an HIV+ patient?
Cryptococcus neoformans
38
Which key test is used to diagnose cryptococcal meningitis?
Cryptococcal antigen - ideally on CSF sample but culture may be used
39
What is the treatment for cryptococcal meningitis?
4 weeks induction treatment of liposomal amphiteracin B and flucytosone...followed by 6 weeks fluconazole
40
What are the most common causes of a mass lesion on brain imaging in HIV?
Toxoplasmosis Primary CNS lymphoma TB
41
How might toxoplasmosis infection present neurologically in an HIV patient?
Headache Rapidly evolving (1-2 weeks) neurological deficit i.e. movement disorder, hemiparesis, visual field defects, dysphasia Encephalitis Myelopathy or cauda equina syndrome may occur due to spinal cord involvement although this is more rare
42
True / False: Toxoplasmosis is such a common opportunistic infection that all HIV+ patients should be given primary prophylaxis for it
False - The risk of developing toxoplasma encephalitis is 12-30% in a patient with existing asymptomatic infection (IgG +ve). These patients should receive primary prophylaxis for toxoplasmosis infection if their CD4 count drops 200 for 6 months
43
Reactivation of which virus causes progressive multifocal leucoencephalopathy?
JC virus
44
What is the presentation of CMV encephalitis?
Rapidly evolving encephalitis, particularly affecting brain stem Cranial nerve palsies Seizures
45
What is the diagnostic method for identifying CMV encephalitis?
CMV DNA isolated from CSF PCR
46
What is the treatment for CMV encephalitis?
Ganciclovir ± foscarnet
47
What is the typical appearance of PCP on chest radiograph?
Bilateral, perihilar interstitial infiltrates
48
What is the main treatment for PCP?
Co-trimoxazole | Steroids according to the PaO2
49
What is the alternative treatment for PCP e.g. if patient experiences toxicity or if failure to respond?
Clindamycin PO or IV, and oral primaquine
50
What are the indications for an HIV patient having primary prophylaxis of PCP?
CD4 under 200 or less than 14% of total lymphocyte count | Hx of other AIDS defining illness
51
What are liposomal amphotericin B and flucytosine used to treat? Give a side effect of each.
First-line treatment for cryptococcal meningitis Liposomal amphotericin B = Cardiotoxic Flucytosine = Toxic to bone marrow
52
How do you calculate the risk of acquiring HIV with an episode of UPSI?
Risk of someone being HIV +ve x Risk of the act = Risk of acquiring HIV at that episode Example: 1 in 10 MSM in London is HIV +ve x 1 in 100 risk of R-UPAI with HIV+ve = 1 in 1000
53
When might you give someone post exposure prophylaxis for HIV?
If risk of acquiring HIV in that episode was > 1 in 1000...and if the episode occurred within last 72 hours
54
True / False: All pregnant women are screened for HIV
True
55
What is the risk of transmission of HIV to the baby from an HIV+ve mother who is on HAART and has an undetectable viral load?
About 0.1%
56
What is the risk of transmission of HIV in the following circumstances: - Unprotected receptive anal sex with an HIV+ individual - Unprotected insertive anal sex with an HIV+ individual
Risk of transmission is 1 in 100 if receptive, and 1 in 1000 if insertive...but remember risk varies depending on viral load
57
True / False: Male circumcision decreases the rate of HIV transmission
True
58
Which infection are HIV+ve patients particularly prone to if CD4 falls below 200?
Pneumocystis pneumonia
59
Which infection(s) are HIV+ve patients particularly prone to if CD4 falls below 100?
Toxoplasmosis Cryptococcus Oesophageal candidiasis
60
Which infection(s) are HIV+ve patients particularly prone to if CD4 falls below 50?
Disseminated CMV | Disseminated mycobacterium avium
61
``` Which type of HIV antiretroviral drugs cause: Insulin resistance Hyperlipidaemia Lipid deposition at trunk Increased cardiovascular risk Nephrolithiasis ```
Protease inhibitors
62
``` Which type of HIV antiretroviral drugs cause: Peripheral neuropathy Myopathy Pancreatitis Hepatis steatosis Lactic acidosis ```
Nucleoside reverse transcriptase inhibitors
63
``` Which type of HIV antiretroviral drugs cause: Rash Hepatitis Vivid dreams Insomnia ```
Non-Nucleoside reverse transcriptase inhibitors
64
What type of drug is raltegravir?
An integrase inhibitor
65
What is the risk of an MSM in London being HIV+ve?
1 in 10
66
What are the EBV driven cancers associated with HIV?
Non-Hodgkin's lymphoma Primary CNS lymphoma Hodgkin's lymphoma
67
What are the HSV driven cancers associated with HIV?
Castleman's disease | Kaposi's sarcoma
68
What are the HPV driven cancers associated with HIV?
Cervical cancer Anal cancer Head and neck cancer
69
True / False: Antiretroviral therapy is stopped whilst a patient receives chemotherapy for non-hodgkins's lymphoma
False - Antiretroviral therapy gives added benefit to the immune system so ART is given concurrently with chemotherapy
70
How might you be able to differentiate between toxoplasmosis and primary cerebral lymphoma in a history?
Toxoplasmosis = 1-2 week onset, associated with fevers | Primary cerebral lymphoma = 2-8 week onset, no fever
71
What are the features of 'persistent, generalised lymphadenopathy' seen in a well HIV+ve patient
Symmetrical, painless lymphadenopathy Rubbery, non tender lymph nodes No B-symptoms
72
What is the treatment for Guillian Barre syndrome presenting in HIV patients?
The same as non-HIV patients: IVIg and / or plasma exchange
73
What investigations are done in a lumbar puncture in HIV?
Biochemistry: Glucose (remember to compare with serum glucose), protein Microbiology: WCC, gram stain, CrAg, India Ink, AFB, fungal cultures Virology: CMV, HSV, VZV Remember to measure opening pressure
74
Why is toxoplasmosis serology not very useful in HIV patients?
Lots of HIV patients have underlying, asymptomatic toxoplasmosis infection anyway and serology stays positive for life so the serology result is only useful if it's negative, as this makes the diagnosis highly unlikely
75
What is the treatment for toxoplasmosis?
Sulphadiazine and pyremethamine - Start this empirically without histological diagnosis
76
True / False: Dexamethasone is used in all cases of toxoplasma infection
False - It is reserved for patients with severe mass effect, neurological signs, reduced consciousness. It can make radiological improvement appear more significant than in reality, so it is reserved for severe cases.
77
What does PML stand for?
Progressive multifocal leucoencephalopathy
78
What is the treatment for PML?
Improve immune status with antiretrovirals. No other treatment has been found to be effective.
79
What is HAND?
HIV Associated Neurocognitive Disorder
80
What are the 3 stages of HIV associated neurocognitive disorder?
Asymptomatic neuropsychological impairment (ANI) Mild neurocognitive disorder (MND) HIV associated dementia (HAD)
81
What is the diagnostic definition of asymptomatic neuropsychological impairment (ANI)?
Cognitive impairment at least one SD below the mean in 2 or more cognitive domains, without difficulties in activities of daily living
82
What is the diagnostic definition of mild neurocognitive disorder (MND)?
Cognitive impairment at least one SD below the mean in 2 or more cognitive domains, with mild difficulty in activities of daily living
83
What is the diagnostic definition of HIV associated dementia (HAD)?
Cognitive impairment at least two SD below the mean in 2 or more cognitive domains, with moderate to severe difficulties in activities of daily living
84
How might non-infective retinopathy in HIV manifest on fundoscopy?
Cotton wool spots Micro aneurisms Retinal haemorrhages
85
Why must HSV retinitis be treated prompts?
Can cause acute retinal necrosis and rapid visual loss
86
What is the treatment for HSV keratitis?
Topical acyclovir
87
What is the treatment for HSV retinitis?
Intravitreal foscarnet, followed by 1/52 of IV acyclovir then 6/52 PO acyclovir
88
What 4 issues need to be addressed with an HIV +ve patient in a follow up consultation?
Physical health Mental health Sexual health Medication issues
89
What sexual health topics would you cover in a follow up consultation with an HIV+ve patient?
- Safe sex practices i.e. condoms - Partner status - Disclosure? - STI check required? In females, important to ask about COCP use (anti-retrovirals cause reduced efficacy), any plans for pregnancy, and check cervical smears up to date
90
What topics would you cover in a follow up consultation with an HIV+ve patient who is on anti-retroviral therapy?
Side effects Concurrent medication and any interaction Adherence Evidence of efficacy i.e. undetectable viral load
91
Under what rules can HIV+ve healthcare workers cary out exposure prone procedures?
- They must have 3 monthly viral load monitoring - Joint supervision with consultant OH physician and HIV physician - Be on a register - 2x tests 3/12 apart where viral load is undetectable
92
What is the management of a baby born to an HIV+ve mother?
If low risk (i.e. mother's viral load undetectable) given baby zidovudine for 4-6 after birth If high risk, baby is given HAART
93
What are the parameters of REEBBA?
``` Reason for tested - the patient's and the clinician's Ever tested before Exposure risk Benefits and Basics of testing Agreement ```
94
What is tested in the 3rd generation HIV test?
Antibodies for HIV
95
What is tested in the 4th generation HIV test?
Antigen AND antibodies for HIV
96
How long do the results of a 3rd generation HIV test take to come back?
30 seconds (it's an immediate, point of care test)
97
How long do the results of a 4th generation HIV test take to come back?
4 days (it's a serum blood test)
98
What is the window period for the 3rd generation HIV test?
3 months
99
What is the window period for eh 4th generation HIV test?
4 weeks
100
List some risk factors for exposure to HIV which you would ask about in the 'exposure' section of REEBA
``` MSM - Ask in detail what type, etc. IVDU Any sex with someone from an endemic area? Any sex with known HIV+ve? Sex worker Surgery or transfusions abroad ```
101
What does MRI show in progressive multifocal leucoencephalitis?
Non-enhancing areas of low attenuation on white matter on T1 | Hyperintense lesions on T2
102
How is progressive multifocal leucoencephalopathy diagnosed?
Suggestive MRI | JC virus detected on CSF PCR