HIV & Nervous System - Nicholas

Question 1

What is HIV?

Answer 1

Retrovirus - RNA virus; posessing reverse transcriptase

Question 2

What is HIV able to integrate?

Answer 2

Host genome, where it may appear dormant

Question 3

What are the cell types that HIV infects?

Answer 3

CD4+ (T-helper cells)

Cells lacking CD4 receptor

Question 4

What allows development of resistance?

Answer 4

Rapid replication with many errors with RNA transcription

Question 5

What is HIV?

Answer 5

Virally encoded proteins associated with toxicity

Question 6

What are the transmission of HIV?

Answer 6

1. Vertically
2. Sexually
3. iv DU [Blood products that havent been screened for HIV]

Question 7

What is the natural history of HIV infection untreated?

Answer 7

Following an infection, there is an initial fall in CD4 cell counts during acute seroconversion, levels recover to gradually fall off over time

Question 8

What is the problem with HIV/AIDS?

Answer 8

There is long period of clinical latency where patients can be entirely fit and well but are very infectious towards other people

Question 9

What happens when the CD4 count stops dropping below 300?

Answer 9

Immune system becomes compromised

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Question 10

What are the first symptoms of HIV?

Answer 10

Constitutional

• Weight loss
• Not feeling quite right
• tired

Question 11

When do patients suffer opportunistic diseases?

Answer 11

When the immune system becomes profoundly impaired

Question 12

What are the natural history of HIV infection?

Answer 12

1. Primary Infection
2. Acute HIV syndrome - wide dissemination of virus seeding of lymphoid organs
3. Clinical latency
4. Constitutional symptoms
5. Opportunistic diseases
6. Death

Question 13

Where is the burden of HIV situated in?

Answer 13

Sub-saharan Africa

• Zimbabwe
• South Africa

Question 14

What is England HIV Data 2016?

Answer 14

1. 89,400 estimated infected
2. 11% thought to be unaware
3. 5164 new diagnoses in 2016
4. 42% at diagnosis have CD4 count < 350 cells; 25% < 200
5. 95% sexual transmission; 45% heterosexual
6. ~ 7,500 seek care at C&W

Question 15

What is AIDS?

Answer 15

HIV infections where you are profoundly immunosuppressed and have a complication

Question 16

What arrived in the mid 1990’s?

Answer 16

Anti-retroviral medicaitons

Question 17

Where do different drugs act?

Answer 17

Different stages of the virus life cycle

Question 18

What was the first range of drugs?

Answer 18

Drugs that specifically inhibited the reverse transciption

Enzyme that turn viral RNA to viral DNA

Question 19

What was the second range of drugs?

Answer 19

Protease inhibitors that stopped the assembly of virally encoded proteins

Question 20

What was the third range of drugs?

Answer 20

Integrase inhibitor which are drugs that stop reverse transcribed DNA being inserted into the human genome

Question 21

What did the early drugs have?

Answer 21

Very significant toxicity causing peripheral nerve damage being really intolerable causing changes in metabolism, changes in fat distribution

Question 22

What was estimated in the states 2015?

Answer 22

50% of the people living with HIV will be over the age of 50

Question 23

How can HIV affect the nervous system?

Answer 23

1. Brain
2. Spinal cord
3. Peripheral nerves
4. Muscle
5. Meninges
6. Cranial Neuropahties

Question 24

What are examples of the brain?

Answer 24

1. Encephalitis
2. Dementia
3. Epilepsy
4. Stroke
5. Headache

Question 25

What are examples of spinal cord?

Answer 25

1. Transverse myelitis | 2. Vacuolar Myelopathy

Question 26

What are examples of peripheral nerves?

Answer 26

1. DSPN 2. GBS 3. CIDP 4. Vasculitic Neuropathy 5. Polyradiculitis 6. Autonomic Neuropathy

Question 27

What is an example of muscle?

Answer 27

Myopathy

Question 28

What is an example of meninges?

Answer 28

Meningitis

Question 29

What are the cranial nerves for cranial neuropathies?

Answer 29

1. VII | 2. VIII

Question 30

What are the principles of HIV Neurology?

Answer 30

1. Time Locking 2. Parallel Tracking 3. Layering 4. Unmasking

Question 31

What is Time Locking

Answer 31

Where in that natural history graph is the patient - Relationship to CD4 cell count

Question 32

What is Parallel Tracking?

Answer 32

Involvement of multiple parts of the nervous system

Question 33

What is layering?

Answer 33

Different pathologies superimposed

Question 34

What is unmasking?

Answer 34

Second pathology dominated by subacute first pathologies symptoms e.g. HIVE & Cryptococcus

Question 35

What happens when the CD4 count is less than 50?

Answer 35

Really serious trouble

Question 36

Immunosuppression

Answer 36

You need your immune system to not only prevent infections but to scan body and prevent you from developing cancer

Question 37

What are common in people that are immunosuppressed?

Answer 37

Cancer

Question 38

What is the classical cancer with people living with HIV?

Answer 38

B-cell lymphoma | Driven by Epstein-Bar virus infection

Question 39

What is the definition of Immune Reconstitution Inflammatory Syndrome (IRIS)?

Answer 39

A paradoxical deterioration in clinical status attributable to the recovery of the immune system during HAART.

Question 40

What are other examples in neurological practice for IRIS?

Answer 40

1. Reversal reactions in leprosy 2. MS relapse following pregnancy 3. Cessation of natalizumab in MS 4. Tuberculoma development in treated- TBM 5. Stroke in S pneumoniae meningitis

Question 41

What are the commonest form of IRIS associated with?

Answer 41

1. CNS streptococcus infections | 2. CNS Tuberculosis

Question 42

What are the commonest conditions causing IRIS in CNS?

Answer 42

JCV [causes PML] CNS TB infections Cryptococcus infections

Question 43

What are the clinical risk factors for IRIS?

Answer 43

1. Profoundly Immunosuppressed 2. Viral load falls very rapidly following antiretral viral therapy 3. If you have an underlying opportunistic infections

Question 44

What was dementia caused by?

Answer 44

Viral CNS infections

Question 45

What is dementia called that is HIV related?

Answer 45

Subcortical dementia

Question 46

What are the triad of subcortical dementia?

Answer 46

1. Cognition 2. Motor function 3. Behaviour

Question 47

Why are HIV dementia now only seen?

Answer 47

1. Burnt out - damage sustained prior to cART 2. Late presentation 3. Non-adherence to ARVs 4. Rarely in patients where CNS & systemic infection follow non-parallel course

Question 48

Patients with systemic control of HIV and high CD4 cell counts complaining of:

Answer 48

1. Mild memory problems 2. Slowness 3. Difficulties in concentration 4. Difficulties in planning 5. Difficulties in multi-tasking

Question 49

What did the CHARTER study show?

Answer 49

High level of cognitive impairment in patients living with HIV who are on treatment

Question 50

What are the confounds for HIV cognitive Impairment?

Answer 50

1. Current drug use 2. Hepatitis C co-infection 3. Depression 4. ''Burnt-out'' CNS disease

Question 51

What are the Imaging for HIV dementia?

Answer 51

1. MRI | 2. CSF

Question 52

What are the problems with CPE?

Answer 52

``` Categorical not ordinal Methodology not transparent: Hard to independently validate Weighting for each criterion? ARV-ARV interactions not considered No accounting for the effect of an impaired BBB Anatomy: CSF not “a liquid brain biopsy” Efficacy in brain cells not assessed specifically Toxicity (CNS/CVS) not considered ```

Question 53

Small vessel Disease in HIV

Answer 53

Frequently found on post mortem and MRI; infarct defined as being < 20mm More extensive subcortical WM hyperintensities seen in treated HIV than age-matched controls.* May be important in pathogenesis of HAND (HIV-associated neurocognitive disorders)