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Year 3 Clinical > Human Immunodeficiency Virus: What, How and Who? > Flashcards

Human Immunodeficiency Virus: What, How and Who? Flashcards

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1
Q

Consequences of HIV infection?

A

Causes Acquired Immunodeficiency Syndrome (AIDS), which is a spectrum ranging from opportunistic infections (OIs) to AIDS-related cancers

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2
Q

Prevention of AIDS?

A

Early HIV diagnosis and treatment prevents AIDS

HIV infection itself is preventable

Most individuals with HIV have a near normal LE

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3
Q

What is HIV?

A

A retrovirus; there are 2 types:
• HIV-2 - a simian immunodeficiency virus that originated in West Africa and is mainly confined to this region; it is less virulent than HIV-1

• HIV-1 - originated in central/West African chimpanzees and followed travel routes; this is responsible for the global pandemic

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4
Q

What is CD4+?

A 
CD4+ receptors are a type of glycoprotein found on the surfaces of certain cells:
• Th cells/lymphocytes (AKA CD4+ cells)
• Dendritic cells 
• Macrophages
• Microglial cells

They are the TARGET SITE FOR HIV

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5
Q

Purpose of CD4+ Th lymphocytes?

A

Essential for induction of the adaptive immune response

Recognition of MHC2 antigen-presenting cell (APC)

Activation of B cells and cytotoxic (CD8+) T cells

Cytokine release

i.e: if CD4+ cells are targeted, many other parts of the immune system are also affected

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6
Q

Effect of HIV infection on the immune response?

A
  1. Sequestration of cells in lymphoid tissues - leads to reduction in the no. of circulating CD4+ cells
  2. Reduced proliferation of CD4+ cells
  3. Reduced CD8+ (cytotoxic) T cell activation leads to:
    • Dysregulated expression of cytokines
    • Increased susceptibility to viral infections (inc. HIV)
  4. Reduced antibody class switching results in the antibodies produced having a lower affinity
  5. Chronic immune activation (due to microbial translocation)
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7
Q

Which infections are HIV +ve patients more susceptibile to?

A

VIRAL and FUNGAL infections

Mycobacterial infections (mainly due to epidemiological link, with more TB occurring in places with higher HIV incidence

Infection-induced cancers, e.g: HPV

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8
Q

Normal CD4+ Th cell parameters and when figures are concerning?

A

Normal 500 - 1600 cells / mm3

Risk of opportunistic infection <200 cells / mm3

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9
Q

Replication rates of HIV virus?

A

Rapid replication in the very early and very late stages infection

There is a new generation every 6-12 hours

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10
Q

Describe the immunopathogenesis of HIV infection

A

Primary infection - rapid HIV replication results in reduction of CD4+ count; there is a period of acute HIV syndrome, where there is wide dissemination of the virus and seeding of lymphoid organs

Asymptomatic infection (can last years) - this is where the the HIV replications gradually increases, leading to a gradual reduction in CD4+ count; the patient may eventually develop constitutional symptoms

Symptoms of AIDS - eventually, HIV load has increased maximally and CD4+ count has plummeted; patient develops opportunistic infections and symptoms of AIDS

ADD IMAGE

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11
Q

For HIV, what is the average time to death without treatment?

A

9-11 hours

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12
Q

How does HIV infection infect CD4+ cells?

A

Mainly enters via infection of mucosal CD4+ cells (Langerhans and Dendritic cells), at the vagina, anus, cervical mucosa

Cells are transported to the regional lymph nodes

Infection is established within 3 days and the virus disseminates

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13
Q

How long till infection is established?

A

Within 3 days of entry, i.e: within the 3 days, a patient can be give post-exposure prophylaxis, e.g: high-risk sex, needle-stick injuries

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14
Q

PC of primary HIV infection?

A 
Onset is ~2-4 weeks after infection; most patients (80%) have flu-like symptoms at this stage, usually a combination of:
• Fever
• Maculopapular rash
• Myalgia
• Pharyngitis
• Headache, aspectic meningitis
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15
Q

Risk of transmission during primary HIV infection?

A

VERY HIGH risk

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16
Q

What happens during the stage of asymptomatic HIV infection?

A

Ongoing viral replication produces huge numbers of HIV and there is ongoing CD4+ count depletion; there is also ongoing immune activation

NOTE - this is NOT a latent stage

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17
Q

Risk of transmission during asymptomatic HIV infection?

A

Risk of onward transmission if it remains undiagnosed

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18
Q

Define opportunistic infections (OIs)?

A

Infection cause by a pathogen that does not normally produce disease in a healthy individual

i.e: uses the ‘opportunity’, afforded by a weakened immune system, to cause disease

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19
Q

Examples of OIs that occur in HIV infection?

A

Pneumocystic Pneumonia (PCP)

TB

Cerebral toxoplasmosis

Cytomegalovirus (CMV)

Skin infections:
• Herpes zoster
• Herpes simplex
• Human papilloma virus
• Others, e.g: Penicilliosis, Histoplasmosis
NOTE - these skin infections can also occur in non-immunocompromised individuals but they tend to be more problematic in immunocompromised patients, e.g: more extensive, recurrent, etc

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20
Q

Cause of PCP?

A

Organism is Pneumocystis jiroveci; generally, more common when CD4+ cells <200

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21
Q

PC of PCP?

A

INSIDIOUS ONSET of shortness of breath and DRY cough; these patients do not have sputum or pleuritic chest pain

Also, patients have exercise desaturation (in O2); this is a test that can be used in GP

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22
Q

CXR of PCP?

A

May be normal

If abnormal, usually interstitial infiltrates, reticulonodular markings

NOTE - does not look like a regular pneumonia, in that it does not show typical consolidation but more patchy changes

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23
Q

Other Ix for PCP?

A

Bronchoalveolar Lavage (BAL) and immunofluorescence +/- PCR

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24
Q

Treatment of PCP?

A

High dose co-trimoxazole (+/- steroid)

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25
Prophylaxis of PCP?
Low dose co-trimoxazole
26
PC of TB in HIV +ve patients?
There is epidemiological synergy, explaining the high occurrence of TB in HIV +ve individuals; however, the average Dundonian with HIV would not be expected to have TB ``` The following features are more common in HIV +ve individuals, compared to HIV -ve individuals: • Symptomatic primary infection • Reactivation of latent TB • Lymphadenopathies • Miliary TB • Extra-pulmonary TB • Multi-drug resistant TB • Immune reconstitution syndrome (immune system begins to recover with HIV treatment, but then responds to a previously acquired OI with an overwhelming inflammatory response) ```
27
Cause of cerebral toxoplasmosis?
Toxoplasma gondii; this is very common and becomes latent, without causing issues in most people, however it reactivates with HIV infection This leads to multiple cerebral abscesses and chroioretinitis More common when CD4+ count is <150
28
PC of cerebral toxoplasmosis?
Headache and fever Focal neurological signs Seizures Reduced consciousness Raised ICP
29
Cause of Cytomegalovirus?
Caused by CMV, a very common infection that becomes latent; when it reactivates, it causes retinitis, colitis, oesophagitis Usually occurs when CD4+ count <50
30
PC of CMV?
Reduced visual acuity Floaters Abdominal pain, diarrhoea, PR bleeding NOTE - all patients with a CD4+ count <50 require an ophthalmic screen
31
Explain herpes zoster infections that occur in HIV
May be multi-dermatomal (unusual as tend to be confined to a single dermatome) Also tends to be recurrent
32
Explain herpes simplex infections that occur in HIV
Tends to be extensive and hypertrophic It is also aciclovir resistant
33
Explain human papilloma virus infections that occur in HIV
Extensive, recalcitrant and dysplastic
34
Occurrence of HIV-assoc. neurocognitive impairment?
Caused by HIV-1 It can occur at any CD4+ count, although it is more common the count decreases, resulting in increased immunosuppression
35
PC of HIV-assoc. neurocognitive impairment?
Reduced short-term memory +/- motor dysfunction
36
What is Progressive Multifocal Leukoencephalopathy (PML)?
Demyelinating disease of the CNS, due to JC virus; this virus does not normally cause problems unless immunosuppressed In HIV, there is reactivation of the latent infection; usually, this occurs when the CD4+ count is <100
37
PC of PML?
Rapidly progressive symptoms of: • Focal neurological signs • Confusion • Personality change
38
Other neuro presentation of HIV?
Distal sensory polyneuropathy Mononeuritis multiplex Vacuolar myelopathy Aseptic meningitis Guillan-Barre syndrome Viral meningitis (CMV, HSV) Cryptococcal meningitis Neurosyphilis
39
Describe HIV-assoc. wasting
AKA 'Slim's disease' ``` Always consider HIV is a patient has unexplained cachexia; it occurs for multiple reasons: • Metabolic (chronic immune activation) • Anorexia (multifactorial) • Malabsorption / diarrhoea • Hypogonadism ```
40
What are the AIDS-related cancers?
Kaposi's sarcoma Non-Hodgkins lymphoma Cervical cancer
41
Cause of Kaposi's sarcoma?
Human Herpes Virus 8 (HHV8); it can occur at any CD4+ count but tends to occur at lower counts, due to increased immunosuppression It is a vascular tumour
42
PC of Kaposi's sarcoma?
Tumours can be: • Cutaneous (spongy nodules / papules) • Mucosal • Visceral (pulmonary, GI)
43
Treatment of Kaposi's sarcoma?
Often, if only cutaneous, continue with HAART and it will improve Local therapies can be used for pain If systemic / visceral manifestations, may require chemotherapy
44
Cause of Non-Hodgkins lymphoma?
EBV (also causes Burkitt's lymphoma, primary CNS lymphoma) Can occur at any CD4+ count but more common if lower, due to immunosuppression
45
PC of Non-Hodgkins lymphoma?
With HIV, tends to be more advanced, more likely to have bone marrow inv. and more likely to have CNS inv. B symptoms Extranodal disease
46
Treatment of Non-Hodgkins lymphoma?
As for HIV (add HAART)
47
Cause of cervical cancer, with HIV infection?
HPV; in patients with HIV, there is persistence of HPV infection and rapid progression to severe dysplasias and invasive disease NOTE - HIV testing should be offered to all patients with complicated HPV disease
48
Non-OI symptomatic issues that occur in HIV?
Mucosal candidiasis (oral thrush) Seborrheic dermatitis Diarrhoea Fatigue Worsening psoriasis (CD8+ mediated) Lymphadenopathy Parotitis Epidemiologically linked conditions: • STIs • Hep B • Hep C
49
Haematological manifestations in HIV +ve patients?
Anaemia (affects ~90%) Thrombocytopaenia (ITP) - MUST DO A HIV TEST NOTE - can occur at any CD4+ count but more common if lower, due to increased immunosuppression
50
Causes of the haematological manifestations that occur in HIV +ve patients?
* HIV infection itself * OIs * AIDS malignancies * HIV drugs
51
How is HIV transmitted?
1. Sexual transmission (accounts for the majority of HIV infection); there is a higher prevalence amongst MSM but incidence is almost as high with heterosexual couples 2. Parenteral transmission: • PWIDs (only make up a small proportion of HIV diagnoses) • Infected blood products • Iatrogenic ``` 3. Mother to child: • In-utero / trans-placental • During delivery • During breastfeeding NOTE - if the mother is treated and if viral load is undetectable at delivery, there is a very low risk of transmission to the child ```
52
Factors increased the risk of HIV transmission?
Anoreceptive sex Trauma Genital ulceration Concurrent STI
53
How many people live with undiagnosed HIV?
17%; this is an issue due to transmission of HIV to others Heterosexual male are most likely to be undiagnosed and they are also more likely to present late
54
Who should be tested for HIV?
1. Universal testing is available in high prevalence areas; HIV testing is recommended in all general medical admissions and in all patients registering at GP (patient has the option to decline the test) 2. Opt-out testing in certain clinical settings, e.g: TOP services, GUM clinics, drug-dependent services (as there is a higher prevalence in these setting) and also in antenatal services and assisted conception services (due to risk of undiagnosed HIV in this group) ``` 3. Screening of high risk groups; inc: • MSM • Female partners of bisexual men • PWIDs • Partners of people who have HIV • Adults and children from endemic areas (Sub-Saharan Africa, Caribbean, Thailand) • Sexual partners from endemic areas • History of iatrogenic exposure in an endemic areas ``` 4. Testing in the presence of clinical indicators; when HIV falls within the differential, HIV test should be performed regardless of risk factors
55
How to obtain consent for a HIV test/
1. Explain to patient that they are being offered a HIV test and why 2. What the benefits of testing are (improve long-term health and protect partner) 3. How and when they will receive results 4. Reassure (confidential)
56
When can a HIV test be done if a patient is incapacitated?
Only if it is in the patient's best interest; consent form a relative is NOT required However, if it is safe to do so, wait until the patient regains capacity
57
Lab markers of HIV?
Viral RNA Antigen Antibody ADD IMAGE
58
Define the window period, with regards to HIV testing?
Time between potential exposure to HIV infection and the point when the test will give an accurate result
59
Use of HIV antibody tests?
3rd generation test - detects HIV-1 and HIV-2, both IgM and IgG; the window period is ~20-25 days and it is very sensitive/specific in established infection 4th generation tests - combined antibody and antigen (p24) tests, which shortens the window period by ~5 days NOTE - this has variation but, generally, a -ve 4th generation test, performed at 4 weeks following exposure, is highly likely to exclude HIV infection
60
How are rapid HIV tests performed?
Fingerprick specimen or saliva is used, giving results within 20-30 minutes There are different types: • 3rd generation (Ab only) • 4th generation (Ab / Ag) NOTE - wide variation in performance
61
Advantages of rapid HIV test?
Simple and no lab or venepuncture required No anxious wait Reduce follow-up Good sensitivity
62
Disadvantages of rapid HIV test?
Expensive Quality control Poor positive predictive Not suitable for high volume Perhaps should not be relied on in early infection
63
What is RITA?
Recent Incidence Testing Algorithm - can be used to identify whether an infection occurred within the preceding 4-6 months, by measuring the different type of Abs or the strength of Ab binding This helps with partner notification BUT there is a large margin or error
64
Advantages of RITA?
Surveillance For local epidemiology Assess HIV testing programmes Informs partner notification Safer sex advice Interpretation of CD4+
65
Disadvantages of RITA?
Accuracy, patient distress and criminalisation
66
Other options for HIV testing, for the patient?
Home sampling Home testing

Year 3 Clinical (100 decks)

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