HIV Flashcards
What is meant by a ‘retrovirus’?
Once inside the host cell it uses its own reverse transcriptase enzyme to produce DNA from its RNA genome
What HIV group was responsible for the global pandemic in 1981?
HIV-1 group M
Where is the CD4 glycoprotein found?
Surface of T-helper lymphocytes, macrophages and microglial cells
What cells are the target site for HIV?
CD4+ on T-helper lymphocytes
What are the functions of CD4+ T h lymphocytes?
Recognise MHC2 antigen presenting cell
Activation of B cells
Activation of cytotoxic T cells (CD8+)
Cytokine release
What is the normal CD4+ Th cell count?
500-1600 cells/ mm3
At what CD4+ Th cell count is there a high chance of infection?
<200 cells/ mm3
What affects does HIV have on immune resonse? 5 stages
Sequestration of cells in lymphoid tissue so reduced circulating CD4+ cells in blood stream
Reduced proliferation of CD4+ cells
Reduced CD8+ T cell activation - increased susceptibility to viruses
Reduced antibody switching
Chronic immune activation - leaky gut
What is the average time to death from HIV with no treatment?
9-11 years
How long after exposure to HIV does it take for the infection to become established?
3 days
When do the symptoms of the primary HIV infection show?
2-4 weeks after infection
What are the symptoms of the primary HIV infection?
Fever Pharyngitis Aseptic meningitis Myalgia Headache Maculopapular rash on upper body Often misdiagnosed as cold or flu
What occurs during the asymptomatic phase of HIV infection?
Ongoing viral replication, CD4+ count depletion and immune activation
What is an opportunistic infection?
Infection caused by a pathogen that does not normally produce disease in a healthy individual
What are examples of opportunistic infections in patients with HIV?
Pneumocystic pneumonia (PCP) Tuberculosis Cerebral toxoplasmosis Cytomegalovirus Skin infections HIV-associated neurocognitive impairment Progressive multi-focal leukoencephalopathy Neurological presentation HIV associated wasting Kaposi's sarcoma Non-Hodgkin's lymphoma Cervical cancer
What organism causes pneumocystic pneumonia?
Pneumocystis jiroveci (fungi)
At what CD4 count do HIV patients get pneumocystic pneumonia?
<200
What are the clinical features of pneumocystic pneumonia?
Insidious onset
SOB
Dry cough
Exercise desaturation
What does pneumocystic pneumonia show on CXR?
May be normal
Interstitial infiltrates and reticulonodular markings
How can pneumocystic pneumonia be diagnosed?
Bronchoalveolar lavage (BAL) Immunofluorescence +/- PCR
How is pneumocystic pneumonia treated?
High dose co-trimoxazole +/- steroid
What organism causes cerebral toxoplasmosis?
Toxoplasma gondii
At what CD4 count do patients get cerebral toxoplasmosis?
<150
What are the signs and symptoms of cerebral toxoplasmosis?
Multiple cerebral abscesses Headache Fever Focal neuro - weaknes Seizures Raised ICP Chorioretinitis Decreased consciousness Multiple ring enhancing lesions
What infections does CMV cause?
Retinitis (most common)
Oesophagitis
Colitis
Whats does a CMV infection present with?
Reduced visual acuity Floaters in eye Abdo pain Diarrhoea PR bleed
What screening should be done for all patients with a CD4+ of less than 50
Ophthalmic screening
What sort of skin infections do HIV patients get?
Herpes zoster Herpes simplex HPV Pencilliosis Histoplasmosis
What virus causes progressive multifocal leukoencephalopathy?
JC virus (reactivation of latent infection)
At what CD4 count do HIV patients present with progressive multifocal leukoencephalopathy?
<100
How does progressive multifocal leukoencephalopathy present?
Rapidly progressive
Focal neurology
Confusion
Personality change
What is HIV associated wasting?
Slim’s disease - cachexia
What is the aetiology of HIV associated wasting?
Metabolic - chronic immune activation
Anorexia
Malabsorption/ diarrhoea
Hypogonadism
What virus causes Kaposi’s sarcoma?
Human herpes virus 8 (HHV)
How can Kaposi’s sarcoma present?
Cancer that is:
Cutaneous
Mucosal
Visceral (pulmonary, GI)
What is the treatment for Kaposi’s sarcoma?
HAART
Liquid nitrogen
Systemic chemotherapy
What causes non-Hodgkin’s lymphoma?
EBV - burkitt’s lymphoma, primary CNS lymphoma
How does non-Hodgkin’s lymphoma present?
B symptoms
Bone marrow involvement
Extranodal disease
CNS involvement
How is non-Hodgkin’s lymphoma treated?
HAART
How often are women with HIV screened for cervical cancer?
Every year (instead of every 3)
Why does psoriasis get worse in HIV?
CD8 cells
Why does rheumatoid get better in HIV?
CD4 cells
What are the modes of HIV transmission?
Sexual
Parenteral - drug use, infected blood products
Mother to child - in-utero, delivery, breast feeding
Why is the rectum vulnerable to HIV?
Only 1 cell thick and full of lymphoid tissue
How should a baby be delivered if the mother has a detectable viral load?
C-section
What are the markers for testing HIV?
Viral RNA
Antigen (capsule protein p24)
Antibody (envelope proteins gp120)
What is the window period of HIV?
Have HIV but test negative
What is the window period of the 3rd generation HIV antibody tests?
20-25 days
What is the window period of the 4th generation HIV antibody and antigen tests?
14- 28 days
What is the rapid antigen test?
Fingerprick specimen or saliva
Results in 20-30mins
What are the targets for the anti-retroviral drugs?
Reverse transcriptase Integrate Protease Entry - fusion and CCR5 receptor Maturation phase
What type of drug is zidovudine?
Nucleoside analogue reverse transcriptase inhibitor (NARTI)
Is zidovudine useful for asymptomatic patients?
No - does not improve survival when used as a monotherapy
What does HAART stand for?
Highly Active Anti-Retroviral Therapy
What is HAART?
Combination of at least 3 drugs from at least 2 drug classes to which the virus is susceptible
What are examples of HAART drugs?
Tenofovir
Emtricitabine
Efavirenz
What are possible side effects of HAART?
GI Skin - rash, hypersensitivity, Steven-Johnstons CNS - mood, psychosis Renal toxicities Bone - osteomalacia CVS - increased MI risk Anaemia
What HAART drugs cause GI side effects?
Protease inhibitors
Nevirapine
What HAART drugs cause skin side effects?
Abacavir
Nevirapine
What HAART drugs cause CNS side effects?
Efavirenz
What HAART drugs cause renal side effects?
Tenofovir
Atazanavir
What HAART drugs cause bone side effects?
Tenofovir
What HAART drugs cause CVS side effects?
Abacavir
Lopinavir
Maraviroc
What HAART drugs cause haem side effects?
Zidovudine
How do HAART drugs interfere with the liver?
Protease inhibitors - liver enzyme inhibitors
NNRTIs - liver enzyme inducers
