8. HIV Flashcards
What conditions are associated with severe HIV?
Oral thrush - candida albicans Kaposi's sarcoma - raised purple lesions Pneumocystis pneumonia (PCP)
What is the outcome of patients with HIV?
Chronic infection (no cure) but no disability if managed properly.
What is the structure of viruses?
Genome - either RNA or DNA, ds or ss
Capsid protein coat around genome - helical, icosahedral
Lipid envelope/ unenveloped - from host cell membranes
What type of virus is HIV?
Retrovirus - ssRNA gest converted to DNA in cells, transcription into sRNA again.
What is the structure of HIV?
ssRNA
Enveloped
Which cells does HIV infect?
CD4+ cells
- T helped lymphocytes
- Monocytes, macrophages
How does HIV damage hosts?
- Destroys the CD4+ cells
- Inflammation
- Spreads to/infects more cells
How is HIV transmitted?
Sexual contact
Transfusion
Contaminated needles
Vertical - breast milk, transplacental, birth canal
How does HIV enter CD4+ cells?
Binds to CD4 and co-receptors, fuses with the cell and contents released into the cell.
Once in the cell, how does HIV virus replicate?
- Reverse transcription of viral sRNA to DNA by reverse transcriptase enzyme
- Integration of viral DNA into host genome by integrate enzyme.
- Transcription of viral DNA during host replication.
- Budding of immature virus
- Maturation of immature virus - proteases
What symptoms and signs might be present during the primary infection stage of HIV?
Flu-like or asymptomatic
What happens during the primary infection phase of HIV?
Viral load is very high as virus enters tissue and lymph nodes, temporary drop in CD4+ cells.
What happens in the latent infection phase?
Viral load decreases to a viral “set point”
The lower the set point, the longer it takes for viral load to increase again.
Which stage(s) of HIV progression are asymptomatic?
Primary infection can be asymptomatic
Latent phase is asymptomatic
How long can the latent phase last?
Months- years
What happens in stage 3/symptomatic infection phase?
The viral load has increased and CD4+ cells are < 350 cells/ul.
What happens in stage 4/ severe infection?
AIDS develops.
<200ul CD4+ cells.
Aids defining illnesses present.
What are the main symptoms of acute HIV infection?
Systemic - fever, weight loss Lymphadenopathy Rash Hepatomegaly and splenomegaly Nausea and vomiting Sores and oral thrush Myalgia
What aids-defining illness’ occur when CD4+ cells reach 200ul?
PCP
Toxicoplasmosis
What disease develops when CD4+ falls to 100ul?
Lymphoma
CMV
What factors affect HIV transmission?
Type of exposure - anal sex is most risky
Viral load - transmission unlikely if undetectable
Condom use
Breaks in skin or mucosa
What diagnostic tests can be used for HIV?
- Serology
- PCR
- “Rapid tests”
How can HIV be detected using serology?
Both HIV antigen and HIV antibody
What are the advantages and disadvantages of using serology to diagnosis HIV?
Results the same day
Can detect after 4 weeks, may get false negative result if taken too early
How can PCR be used to diagnose HIV?
Detect HIV nucleic acid
What are the advantages and disadvantages of using PCR to diagnose HIV?
Highly sensitive
Detects very early (few days)
But expensive, and results are slow (1 wk) so not used in initial screening
How do rapid tests diagnose HIV?
Detect HIV antibody
What are the advantages and disadvantages of using rapid tests?
Easy and quick - can be used for in home or postal testing
Blood test (finger prick) or oral (saliva)
If positive, need serology to confirm
If negative then accurate
What are the aims of HIV treatment?
- Undetectable viral load
- Raise CD4+ count
- Reduce general inflammation
- Reduce risk of transmission
- Normalise lifespan and QoL
Why is there no HIV vaccine at present?
Viral envelop antigens are constantly changing during replication.
What drugs are used to manage HIV?
Anti-retroviral drugs (ARVS)
What proteins can ARVS target?
- Inhibit virus binding and fusing
- Inhibit reverse transcriptase
- Inhibit integrase
- Inhibit protease
How many ARVS should be given?
3 in total: 2 x Nucleoside RT inhibitor and 1 other, either: Non-nucleoside transcription inhibitor Protease inhibitor Integrase inhibitor CCR5 entry inhibitor
Why are 3 ARVS given?
Viral replication occurs at a rapid rate so resistance to drugs develops very quickly. Using 3 helps to overcome this.
What other strategies can be used to treat and reduce HIV?
- Increase condom usage
- Prevent mother-child transmission
- ARV as prevention
- Post-exposure prophylaxis (PEP)
- Pre-exposure prophylaxis (PrEP)
What ethical dilemma’s can be involved in HIV diagnosis?
- Psychological impact
- Dealing with stigma
- Patient confidentiality vs health of mother, unborn child, sexual contact, older siblings and risk to other patients and healthcare workers.