HIV Flashcards
What is the mechanism of action of nucleoside reverse transcriptase inhibitors?
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.
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?
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.
List some key side effects of nucleoside reverse transcriptase inhibitors (NRTIs)
Peripheral neuropathy Myopathy Pancreatitis Hepatis steatosis Lactic acidosis
List some key side effects of non-nucleoside reverse transcriptase inhibitors
Rash
Hepatitis
Vivid dreams
Insomnia
What is the mechanism of action of protease inhibitors?
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.
Which key protease inhibitor can be used in conjunction with other protease inhibitors to enhance their effect? Why?
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
List some side effects of protease inhibitors
Insulin resistance Hyperlipidaemia Lipid deposition at trunk Increased cardiovascular risk Nephrolithiasis
What is the mechanism of action of integrase inhibitors?
Prevents viral DNA from being incorporated into the host genome (a process usually catalysed by integrase enzyme)
What is CCR5?
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
What is gp-120?
This is a protein on the HIV surface which binds to CD4 on the host cell to enable entry.
What is the mechanism of action of a ‘fusion inhibitor’?
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
List the 6 different types of antiretroviral therapies used in the UK
Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Integrase inhibitors
Protease inhibitors
Fusion inhibitors
CCR5 receptor antagonists
Which oncogenic virus is responsible for causing Kaposi’s Sarcoma, and how is the virus transmitted?
Human Herpesvirus 8 (HH8) - transmitted vertically or horizontally
Which organ systems are mostly affected by Kaposi’s Sarcoma?
Skin Mouth Lung Stomach Eyes
How might a patient with primary cerebral lymphoma present?
Headaches
Focal neurology
Onset over 2-8 weeks
No fever
What might brain imaging show in primary cerebral lymphoma?
Multiple, ring enhancing lesions which are periventricular
Mass effect
Cerebal oedema
What is the difference between lesions on brain imaging seen in toxoplasmosis Vs. primary cerebral oedema
The location of lesions tends to indicate the cause:
Toxoplasmosis = Basal ganglia
Primary cerebral oedema = Periventricular
List some common malignancies associated with increased risk in HIV
Lymphoma - particularly Non-Hodgkin’s (systemic NHL and primary cerebral lymphoma)
Cervical
Anal
Castleman’s Disease
What is Castleman’s Disease?
Lymphoproliferative disorder associated with Kaposi’s Sarcoma herpesvirus (HHV-8). Patients present with fever, lymphadenopathy, hepatosplenomegaly and systemic symptoms.
What is the treatment for pulmonary cryptococcal infection in an HIV+ patient?
Fluconazole or, if more severe, liposomal amphoteracin and flucytosine
True / False - About 5% of new TB cases per year are attributed to HIV
False - About 12% of new TB cases each year are attributable to HIV infection
Why is sputum culture less useful for diagnosing TB infection in an HIV positive patient?
HIV positive individuals have a higher rate of extra-pulmonary TB so diagnosis would be useless in these cases.
Why may rifampicin be inappropriate for the treatment of TB in an HIV positive individual?
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.
List 10 infections which might affect the eye in HIV
Cytomegalovirus Herpes simplex virus Varicella zoster virus Toxoplasmosis Tuberculosis Chlamydia Infective choroiditis Gonorrhoea Cryptococcus Syphilis
What is the most common opportunistic infection of the eye which affects HIV patients?
CMV retinitis
What is the treatment for CMV retinitis?
Intraocular ganciclovir
Systemic treatment also required to prevent spread - Valganciclovir PO, or ganciclovir IV
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.
What are the two main problems associated with HSV infection of the eye in HIV?
HSV keratitis
HSV retinitis
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.
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
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.
What is the typical presentation of gonorrhoea affecting the eye in HIV?
Acute, purulent conjunctivitis
How does a cryptococcal infection affect the eye in HIV?
Cryptococcal meningitis can cause swelling of the optic disc and atrophy if untreated
In what way can malignant processes affect the eye in HIV (list 3 pathologies)?
Kaposi’s sarcoma
Lymphoma
Squamous cell carcinoma of the conjunctiva
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
Which nerve palsy is particularly common in the asymptomatic phase of HIV infection?
VIIth nerve palsy
What is the most common organism to cause meningitis in an HIV+ patient?
Cryptococcus neoformans
Which key test is used to diagnose cryptococcal meningitis?
Cryptococcal antigen - ideally on CSF sample but culture may be used
What is the treatment for cryptococcal meningitis?
4 weeks induction treatment of liposomal amphiteracin B and flucytosone…followed by 6 weeks fluconazole
What are the most common causes of a mass lesion on brain imaging in HIV?
Toxoplasmosis
Primary CNS lymphoma
TB
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
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
Reactivation of which virus causes progressive multifocal leucoencephalopathy?
JC virus
What is the presentation of CMV encephalitis?
Rapidly evolving encephalitis, particularly affecting brain stem
Cranial nerve palsies
Seizures
What is the diagnostic method for identifying CMV encephalitis?
CMV DNA isolated from CSF PCR
What is the treatment for CMV encephalitis?
Ganciclovir ± foscarnet
What is the typical appearance of PCP on chest radiograph?
Bilateral, perihilar interstitial infiltrates
What is the main treatment for PCP?
Co-trimoxazole
Steroids according to the PaO2
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
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
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
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
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
True / False: All pregnant women are screened for HIV
True
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%
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
True / False: Male circumcision decreases the rate of HIV transmission
True
Which infection are HIV+ve patients particularly prone to if CD4 falls below 200?
Pneumocystis pneumonia
Which infection(s) are HIV+ve patients particularly prone to if CD4 falls below 100?
Toxoplasmosis
Cryptococcus
Oesophageal candidiasis
Which infection(s) are HIV+ve patients particularly prone to if CD4 falls below 50?
Disseminated CMV
Disseminated mycobacterium avium
Which type of HIV antiretroviral drugs cause: Insulin resistance Hyperlipidaemia Lipid deposition at trunk Increased cardiovascular risk Nephrolithiasis
Protease inhibitors
Which type of HIV antiretroviral drugs cause: Peripheral neuropathy Myopathy Pancreatitis Hepatis steatosis Lactic acidosis
Nucleoside reverse transcriptase inhibitors
Which type of HIV antiretroviral drugs cause: Rash Hepatitis Vivid dreams Insomnia
Non-Nucleoside reverse transcriptase inhibitors
What type of drug is raltegravir?
An integrase inhibitor
What is the risk of an MSM in London being HIV+ve?
1 in 10
What are the EBV driven cancers associated with HIV?
Non-Hodgkin’s lymphoma
Primary CNS lymphoma
Hodgkin’s lymphoma
What are the HSV driven cancers associated with HIV?
Castleman’s disease
Kaposi’s sarcoma
What are the HPV driven cancers associated with HIV?
Cervical cancer
Anal cancer
Head and neck cancer
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
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
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
What is the treatment for Guillian Barre syndrome presenting in HIV patients?
The same as non-HIV patients: IVIg and / or plasma exchange
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
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
What is the treatment for toxoplasmosis?
Sulphadiazine and pyremethamine - Start this empirically without histological diagnosis
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.
What does PML stand for?
Progressive multifocal leucoencephalopathy
What is the treatment for PML?
Improve immune status with antiretrovirals. No other treatment has been found to be effective.
What is HAND?
HIV Associated Neurocognitive Disorder
What are the 3 stages of HIV associated neurocognitive disorder?
Asymptomatic neuropsychological impairment (ANI)
Mild neurocognitive disorder (MND)
HIV associated dementia (HAD)
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
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
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
How might non-infective retinopathy in HIV manifest on fundoscopy?
Cotton wool spots
Micro aneurisms
Retinal haemorrhages
Why must HSV retinitis be treated prompts?
Can cause acute retinal necrosis and rapid visual loss
What is the treatment for HSV keratitis?
Topical acyclovir
What is the treatment for HSV retinitis?
Intravitreal foscarnet, followed by 1/52 of IV acyclovir then 6/52 PO acyclovir
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
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
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
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
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
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
What is tested in the 3rd generation HIV test?
Antibodies for HIV
What is tested in the 4th generation HIV test?
Antigen AND antibodies for HIV
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)
How long do the results of a 4th generation HIV test take to come back?
4 days (it’s a serum blood test)
What is the window period for the 3rd generation HIV test?
3 months
What is the window period for eh 4th generation HIV test?
4 weeks
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
What does MRI show in progressive multifocal leucoencephalitis?
Non-enhancing areas of low attenuation on white matter on T1
Hyperintense lesions on T2
How is progressive multifocal leucoencephalopathy diagnosed?
Suggestive MRI
JC virus detected on CSF PCR
