Human immunodeficiency virus (HIV) Flashcards
(106 cards)
1
Q
Describe the virology of HIV
A
RNA retrovirus
2 types (HIV-1 and HIV-2)
Replicated very early or very late in infection
New generation every 6-12 hours
No proof-reading to mutations retained
2
Q
How does HIV replicate
A
Surface antigens bind to CD4 receptors and CCRS co-receptors on host cell surface
RNA forms DNA via reverse transcriptase
DNA integrated into host genome
DNA codes for viral proteins which exocytose from cell to form a mature virion
3
Q
Which HIV strain is responsible for the global epidemic
A
HIV-1 group M
4
Q
What are the 2 main surface antigens on HIV
A
- GP120
- GP41
5
Q
How is HIV introduced to the body
A
Infection of mucosal CD4+ cells (Langerhans and dendritic cells)
Then transported to regional lymph nodes, where infection established within 3 weeks
Disseminated around the body
6
Q
What cells have the CD4 glycoprotein on their surface
A
- T-helper cells
- Dendritic cells
- Macrophages
- Microglial cells
7
Q
What are some roles of Th cells
A
- Recognition of MHCII APCs
- Activation of B cells
- Activation of cytotoxic T-cells (CD8+)
- Cytokine release
8
Q
What are some effects of HIV on the immune system?
A
- Reduced circulating CD4+ cells
- Reduced CD4+ proliferation
- Reduced CD8+ T-cell activation and dysregulated cytokine expression
- Reduced antibody class switching and lower affinity antibody production
- Chronic immune activation
9
Q
What are the main complications of weakened immune system in HIV
A
Increased susceptibility to viral, fungal, parasitic, mycobacterial infections and infection-induced cancers
10
Q
Normal CD4+ T-helper cell levels
A
500-1600 cells/mm3
11
Q
What CD4+ T-helper cell level carried the highest risk of opportunistic infection
A
<200cells/mm3
12
Q
What is the average time from primary infection to death without treatment for HIV
A
9-11 years
13
Q
How quickly do symptoms occur in primary HIV infection
A
2-4 weeks after infection
14
Q
Presentation of primary HIV infection
A
- fever
- Rash (Maculopapular)
- Myalgia
- Pharyngitis
- Headache/Aseptic meningitis
15
Q
What is occurring during asymptomatic HIV infection
A
Ongoing viral replication
Ongoing CD4 count depletion
Ongoing immune activation
Risk of onwards transmission
16
Q
What does AIDS stand for
A
Acquired ImmunoDeficiency syndrome
17
Q
What is AIDS
A
The condition of opportunistic infections of cancers in HIV
18
Q
What is an opportunistic infection
A
An infection caused by a pathogen that does not normally produce disease in a healthy individual
19
Q
Common bacteria in AIDS
A
- Mycobacterial tuberculosis
- Recurrent pneumonia
20
Q
Common viruses in AIDS
A
- HSV
- Cytomegalovirus retinitis
- PML
21
Q
Common parasites in AIDS
A
- Cerebral toxoplasmosis
- Reactivation of American trypanosomiasis
22
Q
Common fungi in AIDS
A
- Pneumocystis jiroveci pneumonia
- Candidiasis of oesophagus or bronchi
- Histoplasmosis
23
Q
What is PCP?
A
PneumoCystis Pneumonia
24
Q
What is the causative organism in PCP
A
Pneumocystis jiroveci
25
CD4+ Th threshold for PCP
<200
26
Symptoms of PCP
Insidious onset
SOB
Dry cough
27
Signs of PCP
Exercise oxygen desaturation
28
CXR findings in PCP
- May be normal
- Interstitial infiltrates
- Reticulonodular markings
29
Diagnosis of PCPO
BAL + Immunofluorescence ± PCR
30
Management of PCP
High dose co-trimoxazole ± Steroids
31
Prophylaxis of PCP
Low dose co-trimoxazole
32
What are some common TB syndromes in AIDS
- Symptomatic primary infection
- Reactivation of latent TB
- Lymphadenopathies
- Miliary TB
- Extra-pulmonary TB
- Multi-drug resistant TB
- immune reconstitution syndrome
33
What is the causative organism of cerebral toxoplasmosis
Toxoplasmosis gondii
34
CD4 Th threshold for cerebral toxoplasmosis
<150
35
How does cerebral toxoplasmosis cause problems in AIDS
Reactivation of latent infection causing:
- Multiple cerebral abscess
- Chorioretinitis
36
CD4+ Th threshold for CMV in AIDS
<50
37
Presentation of reactivated CMV in AIDS
- Reduced visual acuity
- Floaters
- Abdominal pain, diarrhoea, PR bleeding
38
Presentation of reactivated cerebral toxoplasmosis in AIDS
- Headache
- Fever
- Focal neurology
- Seizures
- Reduced consciousness
- Raised ICP
39
How does CMV cause problems in AIDS
Reactivation of latent infection causing:
- Retinitis
- Colitis
- Oesophagitis
40
What is offered to all HIV patients with a CD4 level <50
Ophthalmic screening for CMV retinitis
41
What is HIV-associated neurocognitive impairment
Reduced short term memory and motor dysfunction caused by HIV-1 infection of microglial cells of the brain
42
What organism causes PML?
Reactivation of JC virus
43
What does PML stand for in AIDS
Progressive Multifocal Leukoencephalopathy
44
What is the CD4 threshold for PML
<100
45
Presentation of PML in AIDS
- Rapidly progressing
- Focal neuropathy
- Confusion
- Personality change
46
What are some skin infections that can occur in AIDS
Herpes Zoster
Herpes Simplex
Human Papilloma virus
47
Characteristics of Herpes Zoster in AIDS
Multi-dermatomal
Recurrent
48
Characteristics of Herpes Simplex in AIDS
- Extensive
- Hypertrophic
- Aciclovir resistant
49
Characteristics of HPV in AIDS
- Extensive
- Recalcitrant
- Dysplastic
50
What is HIV-associated wasting (Slim's disease)
Involuntary weight loss exceeding 10% of baseline body weight, along with diarrhoea or weakness and fever lasting over 30 days.
51
Causes of HIV-associated wasting
- Metabolic (Energy usage by chronic immune activation)
- Anorexia
- Malabsorption/diarrhoea
- Hypogonadism
52
What are some examples of HIV-related cancers in AIDS
Kaposi's sarcoma
Non-Hodgkin lymphoma
Cervical cancer
53
What organism causes Kaposi's sarcoma in AIDS
Human Herpes Virus 8
54
Pathology of Kaposi's sarcoma
Vascular tumour
55
Locations of Kaposi's sarcoma
- Cutaneous
- Mucosal
- Visceral (Pulmonary, GI)
56
Treatment of Kaposi's sarcoma
- Anti-retrovirals
- Local therapies
- Systemic chemotherapy
57
Organism responsible for Non-Hodgkin's lymphoma in AIDS
EBV
58
Presentation of Non-Hodgkin's lymphoma in AIDS
- More advacnes
- B symptoms
- Bone marrow involvement
- Extra-nodal disease
- Increased CNS involvement
59
What are some non-AIDS symptoms of HIV
- Mucosal candidiasis
- Seborrhoeic dermatitis
- Diarrhoea
- Fatuigue
- Worsening psoriasis
- Lymphadenopathy
- Parotitis
60
What are some epidemiologically linked conditions with HIV
STIs
Hepatitis B and C
61
What are some neurological presentations of HIV
- Distal sensory polyneuropathy
- Mononeuritis multiplex
- Vacuolar myelopathy
- Aseptic meningitis
- Guillain-Barre syndrome
- Viral meningitis
- Cryptococcal meningitis
- Neurosyphilis
62
What causes haematological complications of HIV
- HIV itself
- Opportunistic infections
- AIDS-malignancies
63
What are some forms of haematological presentations of HIV
Leukopenias
Lymphopenias
Thrombocytopenia (HIV infects megakaryocytes)
64
What are the 3 main modes of HIV transmission
Sexual (92% UK)
Parenteral transmission
Mother-to-child
65
What are some ways in which HIV is NOT spread (Common myths)
Oral sex
Biting
Kissing
Contact with eyes
66
What are some factors which increase risk of HIV transmission during sex?
- Anoreceptive sex
- Trauma
- Genital ulceration
- Concurrent STI
67
Is MSM or MSW more common in causing HIV spread in the UK
Sex between men and women (39.8% new cases)
(MSM 30%)
68
What are some forms of parenteral HIV transmission
Injection drug use
Infected blood products
Iatrogenic
69
What are some ways in which HIV can be spread from mother to child?
In-utero
During delivery
During breast feeding
70
How common is mother-to-child spread in untreated patients?
25%
71
What is the mortality rate of HIV+ babies?
33% before 1st birthday
72
How common is HIV globally
Globally, 39 million people are living with HIV, with 37.5 million of these being adults (15+):
- 20 million - Women
- 17.4 million - men
73
Where in the world is the highest (and lowest) HIV incidence
There is a much higher incidence in Africa and a raised incidence in the americas:
- Sub-Saharan Africa
- Caribbean
- Thailand
Lowest rates are in the middle east
74
Most at-risk groups for HIV
- Men who have sex with men (MSM) 1:17 (1:7 in London)
- Black African men 1:25
- Black African women 1:23
- People who inject drugs 1:263
75
What are the 4 types of HIV screening programmes?
- Universal testing in high prevalence areas
- Opt-out testing in certain clinical settings
- Screening of high-risk groups
- Testing in the presence of clinical indicators
76
Who is tested in "universal testing in high prevalence areas"
All general medical admissions or all new GP registrations in:
High prevalence areas (>0.2%)
77
What services offer opt-out HIV testing due to high risk patients
- Termination of pregnancy services
- Sexual health services
- Addiction and substance misuse services
- Antenatal services
- Assisted conception services
78
How can HIV be tested for?
- Viral RNA
- Capsule protein p24
- HIV antibodies
79
What is detectible in the first 3 months on HIV testing?
Viral RNA
p24
80
What is detectable after 45 days on HIV testing?
Antibodies
81
How is antibody HIV testing carried out out
Fingerpick blood sample (Ready within 20-30 minutes)
82
What are some individual barriers to HIV testing
- Perceived risk
- Fear
- Confidentiality
83
What are some healthcare barriers to HIV testing
- Knowledge
- Experience
- Don’t want to offend
84
What are some structural and systemic barriers to HIV testing
- Cost
- Accessibility
- Stigma
85
What are some targets for antiretroviral drugs
- Reverse transcriptase
- Integrase
- Protease
- Entry - Fusion and CCR5 receptor (on host)
- Capsid
- Monoclonal antibodies
- Maturation (In the pipeline)
86
What is the main treatment regime for HIV
Highly active anti-retroviral therapy (HAART)
87
What is involved in highly active anti-retroviral therapy (HAART)
a combination of 3 drugs from at least 2 drug classes to which the virus is susceptible
Now available as a single tablet
88
What is the purpose of HAART
reduced viral load to undetectable levels, restores immunocompetence, reduces morbidity and mortality and prevents onward transmission
89
Why is it important that patients take HAART regularly
even some missed doses can lead to HIV resistance
90
How is life-expectancy affected in HIV
Life-expectancy is improviong towards normal
Young people started on HAART with a CD4>500 may have a longer life than those without HIV, however, the quality of life is worse
91
How can some HAART drugs affect other drugs
protease inhibitors - Liver enzyme inhibitors
NNRTIs - Potent liver enzyme inducers
92
What are some symptoms of HAART toxicity
GI side effects
Rashes, hypersensitivity, Stevens-Johnsons syndrome
Mood and psychosis
Renal toxicity
Osteomalacia
Increased MI risk
Anaemia
Hepatitis
93
What is the law on partner notification
It is a voluntary process by the patient (Murky if parter is also your patient as in a GP)
It is not a legal right for you to tell the partner in every situation
94
How does circumcision decrease HIV risk
Decreases risk by 60%
Foreskin contains a large number of CD4 cells
95
What are some HIV prevention techniques
- Condoms
- Regular testing
- PrEP and PEP
- PMTCT
- Circumcision
- Needle exchange/Drug treatment
96
What does U=U mean
Undetectable = Untransmittable
During treatment, if viral load is undetectable, HIV cannot be transmitted
97
What viral load is classed as undetectable?
<200 cp/ml
98
What form of transmission does not follow the U=U rule
Breastfeeding!
99
What is PrEP?
Pre-exposure prophylaxis
100
What is involved in PrEP?
combination of 2 anti-retroviral drugs given to those at high risk of HIV acquisition
This is usually Tenofovir/Emtricitabine daily or as a long acting injectable
101
What is a risk of PrEP?
risk to renal health and risk of drug-drug interactions so requires regular monitoring
102
What is PEP
Post-Exposure Prophylaxis
103
When should PEP be started?
within 72 hours of high-risk exposure, either sexual or occupational
104
What is involved in PEP?
This is a combination ART taken for 4 weeks consisting of:
- Tenofovir/Emtricitabine
- Raltegravir
105
How effective is PEP?
This is an unlicensed indication and has poor quality data to support, although in some cases shows an 80% reduction in HIV acquisition
106
How can vertical transmission be reduced?
- HAART during pregnancy
- Vaginal delivery if undetected viral load
- Caesarean section if detected viral load
- 2-4 weeks PEP for neonate
- Exclusive formula feeding
