HIV Flashcards
(102 cards)
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
