Session 6 Flashcards
(78 cards)
1
Q
What are infections that occur in immunocompromised people, specifically in AIDS?*
A
- Kaposi’s sarcoma
- Oral candidiasis
- Pneumocystic pneumonia
2
Q
What general pathogenic infections are common in HIV?
A
- Virus reactivations (eg. shingles)
- Fungal infections
- Yeast infections
- Meningitis
- TB
3
Q
What is the outcome of HIV?
A
- Chronic infection +/- disability if treated, can be controlled if diagnosed early and given appropriate treatment
- Death if diagnosed late, progresses to AIDS and left untreated.
4
Q
Who is HIV more common in in the UK?
A
- Men who have sex with men
- Men
- 1/2 are black African
- People who inject drugs
5
Q
Which individuals are usually diagnosed late and therefore have worse outcomes?
A
- People aged > 50
- White heterosexual men
- Black African men
6
Q
How is HIV transmitted (methods)?
A
- Sexual contact
- Blood transfusions (rare now)
- Contaminated needles
- Vertical (transplacental/childbirth/breast milk)
7
Q
What kind of virus is HIV?*
A
- RETROVIRUS -> ssRNA to DNA to ssRNA via reverse transcriptase
- ssRNA so prone to natural rapid mutations
- Lipid bilayer envelope from host cell
- Replicates by incorporating into DNA and then being released from the cell
- Have gp120 (docking) and gp41 (transmembrane) that bind cells with CD4 receptors
8
Q
What cells does the HIV virus infect?
A
- Cells with CD4 surface receptor
- T-helper lymphocytes (monocytes/macrophages)
9
Q
How does HIV infect?
A
- Replicates inside cells
- Destroys cell
- Causes inflammation
- Spreads to more cells
10
Q
Describe the process of HIV infection*
A
- Virus binds to a CD4 molecule and 1 or 2 coreceptors, CCR5/CXCR4
- Virus fuses with cell
- Virus penetrates and empties its contents into cell
- ssRNA converted to dsDNA via reverse transcriptase
- Viral DNA integrated with host DNA via integrase enzyme (incurable)
- Viral DNA cell divides and long chains are made
- Sets of viral protein chains come together
- Budding: immature virus pushes out of cell and takes some membrane, and breaks free
- Protein chains cut by protease into individual proteins that combine to make a working virus
11
Q
How is HIV transmitted?
A
Contact of infected bodily fluid with: - Mucosal tissue - Blood - Broken skin Also medical procedures, like organ donation and blood-blood
12
Q
What is seroconversion?*
A
First stage of HIV infection.
- Normal CD4 cell count at the beginning, then slight drop
- Highest viral load
- Patient very infectious
- Usually asymptomatic
13
Q
What is latent infection?*
A
- Viral load drops to the ‘viral set-point’ : the limit to which the immune system is able to clear infection
- CD4 count starts to fall dramatically
- Virus replicating slowly
14
Q
What is symptomatic infection?*
A
- CD4 count under 350 cells/microlitre
- Virus replicating faster
- Patients start getting unusual infections that they never got before
15
Q
What is severe infection/AIDS?*
A
- CD4 count under 200 cells/microlitre
- High viral load
- Patient usually very unwell and at a very high risk of AIDS-related malignancies and severe diseases
16
Q
What are some symptoms of an ACUTE HIV infection?*
A
- Fever
- Weight loss
- Mouth sores and thrush
- Headaches
- Skin rash
- Nausea and vomiting
- Hepatosplenomegaly
17
Q
Describe what infections become more common as the CD4 count decreases. **
A
< 500 - bacterial and fungal skin infections < 400 - Kaposi's sarcoma < 300 - TB < 200 - PCP, toxoplasmosis < 100 - Lymphoma
18
Q
What are some conditions associated with severe HIV?*
A
- Toxoplasmosis
- Hep C
- Tuberculosis
- Cytomegalovirus
- Pneumocystis jiroveci pneumonia
- HPV and cervical cancer
19
Q
What factors affect HIV transmission?
A
- Type of exposure (eg. higher risk from sexual act than from needlestick injury that was well taken care of)
- Viral load in patient (transmission unlikely if viral load undetectable)
- Condom use
- Breaks in skin/mucosa (eg. sexual assault and STIs)
20
Q
What carries the highest risk of HIV transmission?
A
Blood transfusions. However, these are very rare occurrences as blood donors are screened for HIV.
- Receptive anal intercourse carries a 1/90 risk of transmission.
21
Q
What is the life expectancy of an individual with HIV?
A
78 years
- Early detection
- Treatment and adherence
- Most likely to die from non-AIDS related causes
- LATER DETECTION WORSENS PROGNOSIS
22
Q
What diagnostic blood test should be done for HIV?
A
- Serology
- PCR
- ‘Rapid’ HIV antibody tests
23
Q
What is measured in serology?
A
- HIV antigen (viral protein) and antibody (response)
- Positive in 4 weeks
24
Q
What are some issues with serology?
A
Results on same day BUT may get false negative
25
How is PCR used in diagnosing HIV?
- Detects HIV nucleic acid
- Very sensitive and can detect early infection
- Used for follow-up and treatment responses
26
Why is PCR not used for initial HIV testing?
- Very expensive
| - Results are slow (up to 1 week)
27
What are 'rapid' HIV tests and why are they used?
- Detect HIV antibodies
- Can be fingerprick or saliva
- Can even be done at home
- Used as they are quick and low cost
28
What is an issue with rapid HIV testing?
A person may get a false positive result, and that must be confirmed with serology.
29
Who should be tested for HIV in particular?
Individuals with:
- TB/bacterial pneumonia
- Meningitis
- Shingles
- Chronic weight loss
- Blood abnormalities
- Lymphoma and anal cancer
- STIs
- Hep B and C
30
What drugs are used to prevent HIV transmission and why?
- Anti-retroviral drugs
| - Very low risk of transmission to other individuals
31
What should HIV treatment provide?
- Undetectable viral load
- Strengthened immune system
- Reduced general inflammation
- Reduced risk of transmission
- Good lifespan and life quality
32
How do anti-retroviral drugs work?*
1) Prevent binding to CD4/CCR5/CXCR4 receptors
2) Inhibit reverse transcriptase
3) Inhibit integrase
4) Inhibit protease
33
When should people with HIV start treatment?
ASAP regardless of CD4 counts
34
Which antiretrovirals are used to treat HIV?*
Combination of 3 drugs:
- 2 x nucleoside reverse transcriptase inhibitor (eg. tenofovir/lamivudine)
- 1 x either: NNRTI (doravirine) / protease inhibitor (darunavir) / integrase inhibitor (raltegavir) / CCR5 inhibitor (maraviroc)
35
Why are 3 ARVs given?
- HIV virus mutates every 2-3 replication rounds and replicates many times in a day
- Giving 3 ARVs makes resistance much less likely if patients continue to take drugs every day
36
What reduces HIV prevalence?
- Screening
- ARV
- PEP and PrEP
- Condom use
- Preventing vertical transmission
37
Why are some people immune to HIV?
They do not have the CCR5 receptors on the surface of their cells, meaning that the virus cannot attach to the cell and therefore cannot replicate
38
What are some ethical dilemmas involved in treating HIV?
- Psychological impact of diagnosis
- Stigma
- Risk to other individuals
- Health of person and others associated
39
What is hepatitis?
Inflammation of the liver
40
Where do hepatitis viruses replicate?
- In hepatocytes
| - Will destroy hepatocytes during the process
41
How are Hep B and C transmitted?
B: Blood, sex, vertical
C: Blood & sex
42
What are the incubation periods of Hep B and C?
- B: 6 weeks - 6 months
| - C: 6 - 12 weeks
43
What kind of virus is the one causing Hep B?
HEPADNAVIRIDAE
| - dsDNA enveloped virus
44
What kind of virus is the one causing Hep C?
FLAVIRIDAE
- ssRNA
- Positive strand
- Non-enveloped icosahedral
45
What are the functions of the hepatic system?
- Glycogen storage
- Bile production for fat metabolism
- Clotting factor production
46
What is bilirubin?*
- Breakdown product of haemoglobin (biliverdin that is converted to bilirubin)
47
What is conjugated bilirubin?
Bilirubin that is water soluble and excreteable in faeces and urine
48
What enzyme conjugates bilirubin?
UDP glucuronyl transferase
49
What causes prehepatic jaundice?
Haemolysis - increased breakdown of red blood cells and haemoglobin results in the release of more bilirubin
50
What is cholestatic jaundice and what causes it?
Jaundice occurring in the hepatic system (liver and bile ducts), usually caused by liver damage or inflammation.
51
What causes intrahepatic jaundice (buildup of bilirubin in liver)?*
- Viral and alcoholic hepatitis
- Cirrhosis
- Recurrent cholestasis
- Drugs
52
What causes extrahepatic jaundice and what is it?*
- Occurs when bile cannot flow down to the duodenum and the ducts are blocked
- Caused by:
Carcinomas (bile duct/head of pancreas)
Duct stones
Biliary strictures
53
What does elevated alkaline phosphatase (ALP) indicate?
Damage or obstruction of flow in the biliary tract (cholestasis)
54
What do elevated alanine transaminase (ALT) and aspartate aminotransferase (AST) indicate?
Damage to the hepatocytes and their integrity - allows enzymes to be released.
55
What does decreased albumin indicate?
Liver damage (albumin synthesised in liver)
56
What do low international normalised ratio (INR) and prothrombin time (PT) indicate?
- Low levels of clotting factors
| - Indicate liver damage as clotting factors made in the liver
57
How is Hep B transmitted?
- Vertical (75%)
- Sexual contact
- Drug injecting
- HCW needlestick injuries
58
What are acute symptoms of acute Hep B?
UP TO 50% DO NOT HAVE SYMPTOMS
- Jaundice
- Fatigue
- Abdominal pain
- Anorexia
- Nausea and vomiting
- Arthralgia
59
Is Hep B curable?
The body is able to clear the infection within around 6 months in most cases, but still has a 10% chance to become chronic and <1% will have hepatic failure.
60
What are the outcomes for children compared to adults in Hep B?
- 90% of Hep B infections in children become chronic
| - only 10% progress to chronic in adults
61
What is measured in Hep B serology? (SLIDE 19 + 20!)
- Surface antigen (rise in ALT)
- Then e-antigen when person highly infectious
- CORE ANTIBODY (IgM)
- E-ANTIBODY (no e-antigen, low infectivity)
- Then Surface antibody as a response; last to appear and indicates clearance
- CORE ANTIBODY (IgG) FOR LIFE
62
What is chronic Hep B infection?
Persistence of HBsAg after 6 months
63
What can chronic Hep B infections lead to?
- 25% cirrhosis
| - 5% hepatocellular carcinoma
64
What are treatments for chronic Hep B?
- No cure as integrated into host genome
| - Must receive lifelong anti-viral drugs to suppress replication
65
What are inactive carriers?
Individuals with controlled Hep B, who have normal LFTs and no liver damage. They do not require treatment but monitoring.
66
What are Hep B vaccinations?
- Genetically engineered surface antigens
- Designed to produce long-term surface antibody response
3 doses and boosters if needed.
67
What is present in acute infection?
- Surface antigens
- Core IgM antibody
- Suface antibody (maybe)
68
What is present when an infection was cleared?
- IgG core antibody
| - Surface antibody
69
What is present in chronic infection?
- Surface antigen
| - IgG core antibody
70
What is present in people who have never been infected but were vaccinated?
Surface antibody
71
Who is at risk of Hep C?
- Intravenous drug users (>90%)
- Sexual contact, esp. if HIV too
- Infants born to HC positive mothers
- Blood transfusions
- Needlestick injuries
72
How does Hep C progress?
- 80% chronically infected
| - Some will develop cirrhosis, decompensated liver disease, hepatocellular carcinomas and death
73
What are the symptoms of Hep C?
- 80% NONE
| - 20% vague - RUQ abdo pain, nausea, anorexia, fatigue
74
What serology test is done for Hep C?
Anti Hep-C antibody test
75
Why can the serology test not necessarily detect Hep C?
- The antibody is not protective but will remain long after clearance and cure
- Infection may be cleared
76
What must be used to confirm diagnosis?
Viral PCR test - positive confirms chronic infection
77
What is the treatment for Hep C?
- Directly acting antiviral drug combo
- 8-12 week course
- 90% cure chance
NO VACCINE
78
What is post-exposure prophylaxis?
Drugs given to prevent HIV dissemination and replication in tissue and bodily fluid if there was a risk
- 3x for 28 days
- HIV tests must be done at baseline, 1 month and 3 months
