M28 - HIV Flashcards
what is the definition of virus?
- Very small, non-cellular microbe (10-200 nm).
* Obligate intracellular parasite
What does a virus particle include?
– nucleic acid (DNAorRNA), protein shell (capsid)
– sometimes lipid layer too (envelope)
Describe the unique replication of a virus.
virus genome directs synthesis of virus proteins and
progeny virus genomes using cellular machinery
Describe the assembly of a virus.
The virus components produced by the host cell are assembled into progeny virus particles
What does HIV stand for?
Human immunodeficiency virus
what is HIV?
– Retro virus member of lentivirus family
– Classically Lentivirus linked to long-incubation & long- duration diseases
What 2 types of HIV are recognised?
HIV- 1 and HIV- 2
What does AIDS stand for?
Acquired immunodeficiency disease syndrome
What is AIDS?
– End point disease when severe symptoms become
apparent
– Variety of discrete & overlapping presentations
What is the origin of of HIV?
– HIV-1 Simian immunodeficiency virus (SIV) in chimpanzees
• Cameroon
– Bushmeat consumers & dealers get SIV
• Limited pathology, little/no person to person transmission
what supported the spread of HIV?
High risk activities supported person to person spread.
– HIV-1 M projected to arise in 1910 (BelgianCongo1959)
–Urbinisation /Sexual contact/genital ulcers
what is is recognised as aiding transmission Africa ?
MSM tranmission
what type of virus is HIV?
Retrovirus
what is the genome of HIV?
Genome is RNA but changes to DNA
-contrary to normal DNA-RNA-Protein
what converts RNA to DNA in HIV?
- Reverse Transcriptase
* With other unique enzymes is target for many drugs
why is mutation rate very high in HIV?
RT error prone
How many HIV particle produced daily?
10 ^10
How quickly does it evolve faster than humans?
10^6 faster
What makes HIV difficult to treat?
potential to evolve quickly-, hard for immune sytem to get stabel fix for effective anitbodies for changing surface anitgens
What are the key stages of HIV replication cycle?
1) HIV releases contents into target cell
2) Reverse transcriptase copies viral RNA into DNA
3) Viral DNA is inserted into cellular DNA
4) Many copies of viral RNA and proteins are made
5) New viral particles assemble and bud from cell, potentially killing it
What are the 2 types of replication of HIV in a cell?
- replicate immediately in the cell
- silent route:
what is the key concept of AIDS and HIV?
surface of virus targets CD4 immune cells
when is HIV fatal?
HIV infection always fatal but treatment can control the virus for a sustained period of time
what do replicating HIV in cells carry?
CD4 marker, which are central to immune system
What is meant by the dynamic equilibrium of HIV?
replication versus variation, means waves of virus that host does not have immediate immunity to
When does HIV develop into AIDS?
AIDS is end stage disease caused by HIV, 1- 15 years after infection
What is in the CD 4 glycoprotein?
T-helper cells, monocytes, macrophages &
dendritic cells
what is the role of CD 4 glycoprotein?
Role communicating to other cells including CD8 cells which kill infectious particles
what is co-receptor binding necessary for CD 4 glycoprotein?
– Co-receptor binding necessary for confirmation change and entry :
• Mutations & resistance
• Sex workers
• Long term non-progressors
• CCR-5 co-receptor found as recessive in 10-15% of Eurasia population
What is the diagnosis and monitoring of HIV?
- Anti-HIV antibody/antigen
- Viral RNA (circulating virus)
- CD4 counts
What does weakened immune systems lead to?
increase in rare diseases
Name 3 AIDS -defining illnesses.
- Cytomegalovirus disease
- Esophageal candidiasis
- Histoplasmosis
what occurs frequently in persons living with HIV disease?
Oral presentations : chronic adult peridontitis
What are the 3 key presentations of periodontal disease seen in association with the HIV-infection?
– linear gingival erythema,
– necrotizing ulcerative gingivitis
– necrotizing ulcerative periodontitis
Name 4 oral presentations of HIV.
- Candidiasis
- Angular chelitis
- Linear gingival erythema
- Necrotizing ulcerative periodontitis
what is aphthous ulceration and how can it be treated?
Unknown cause; very painful;
last longer in immunosuppressed;
can treat with topical & occasionally systemic corticosteroids
In what ways is HIV prevented?
• Blood/tissue, and blood products – Needle stick injuries
• Sex
– Abstinence, be faithful & condom use (ABC)
• Mother/child
• Prevention
– Lifestyle & understanding risks key
• Situation in UK
– Homosexual & Heterosexual spread
• Situation worldwide
What Is the rate of HIV transmission for receptive anal sex?
1 in 50
What is the rate of HIV tranmission for a needle stick injury?
1 in 300
What is the rate of HIV transmission for receptive vaginal sex?
1 in 500
How many people were diagnosed with HIV in Scotland in 2017?
HIV 6,000
– 800 undiagnosed
Describe the prevention of HIV?
• Blood/products/tissue: Screen – Ab/Ag – PCR? • Mother/child: • Sex: Education - ABC Microbicides – old vrs new Circumcision Treat STIs Diagnosis – treatment: PEP, PEPSE and PreP
what is the focus for treatment since there is no vaccine?
anti-viral drugs
Name drug targets for treatment.
– Reverse transcription inhibitors e.g.AZT
• New drugs approved referred to as non-nkes (NNRIs)
– Nucleoside based RT inhibitors (NRTIs)
• Pro-drugs become active after phosphorylated by cellular
kinases
• Incorporated into growing DNA but terminate DNA synthesis
• Both RNA & DNA dependent DNA synthesis blocked
– Integrase Inhibitors
– Protease inhibitors
– CCR5 inhibitor (early inhibitors blocking entry)
Describe the treatment of HIV.
• Drug combinations tailored to individual.
– >20drugs
– ART in UK 1996
– 1 or 2x per day
– Ensure viral load is low
– Patients monitored
– Side effects both short & long term
– 20 year old on original ART projected to live to 67 new treatments suggest 78
What does ARV stand for?
antiretroviral drugs
What does cART stand for?
combination ARV treatment
Describe the post-exposure prophylaxis.
• cART – <72 hours Ninewells – 1 or 2x per day – 28 days – Drug combination NHS • NRTIs (Truvada) • Integrase inhibitor (Raltgravir) – Side effects • Headaches • Diarrhoea • Nausea • Vomiting
What needs to be ensured during treatment (post-exposure prophylaxis)?
safe sex
What is significant for dentists for diagnosis?
– no definitive presentation, but some should prompt testing
– 25-30%HIV positives unaware of diagnosis–not usual risk groups
– Late diagnosis ,AIDS or low CD4 count
– Common Presentation of infectious diseases in immune suppressed or malnourished
What is significant for dentist for personal health?
– Ban on HIV+ dentists practising in UK lifted in 2016
– EPP and non-EPPs categorised by bleed-back risk
– Dentist must be on cART,monitored every 2 weeks & <200 copies per ml