HIV

Question 1

What is HIV?

Answer 1

Retrovirus
HIV-2 originated in West African Sootey mangabey
Less virulent
HIV-1 originated in Central/West African chimpanzees: HIV1 group M responsible for global pandemic

Question 2

What is the target site for HIV?

Answer 2

CD4+ receptors

Question 3

What cells are CD4+ receptors found on?

Answer 3

T helper lymphocytes
Dendritic cells
Macrophages
Microglial cells

Question 4

What do CD4+Th lymphocytes do?

Answer 4

Essential for induction of adaptive immune response 
Recognition of MHC2 APC
Activation of B cells
Activation of cytotoxic CD8+ T cells
CK release

Question 5

What effect does HIV infection have on immune response?

Answer 5

Sequestration of cells in lymphoid tissues
-Reduced circulating CD4+ cells
Reduced proliferation of CD4+ cells
Reduction CD8+ (cytotoxic) T cell activation
-Dysregulated expression of cytokines
-Increasing susceptibility to viral infections (including HIV)
Reduction in antibody class switching
-Reduced affinity of antibodies produced
Chronic Immune Activation (microbial translocation)

Question 6

What does HIV increase susceptibility to?

Answer 6

Viral infections
Fungal infections
Mycobacterial infections
Infection-induced cancers

Question 7

At what CD4+Th count is there a risk of opportunistic infection?

Answer 7

<200cells/mm3

Normal is 500-1600

Question 8

Describe HIV viral replication

Answer 8

Rapid in very early and very late infection

New generation every 6-12hours

Question 9

How does HIV spread in the body?

Answer 9

Infection of mucosal CD4 cell (Langerhans/dendritic)
Transport to RLNs
Infection established within 3 days of entry
Dissemination of virus

Question 10

When is the usual onset of HIV?

Answer 10

2-4wks after infection

Question 11

What are the common symptoms of primary HIV infection?

Answer 11

Fever
Rash (maculopapular)
Myalgia
Pharyngitis
Headache/aseptic meningitis
Up to 80% present with symptoms

Question 12

What happens during the asymptomatic HIV infection?

Answer 12

Ongoing replication
Ongoing CD4 count depletion
Ongoing immune activation
Risk of onward transmission if remains undiagnosed

Question 13

What is an opportunistic infection?

Answer 13

An infection caused by a pathogen that does not normally produce disease in a healthy individual. It uses the “opportunity” afforded by a weakened immune system to cause disease

Question 14

What organism causes pneumocystis pneumonia?

Answer 14

Pneumocystis jiroveci

Question 15

What are the symptoms and signs of pneumocystis pneumonia?

Answer 15

Insidious onset
SOB
Dry Cough
Exercise desaturation

Question 16

How is pneumocystis pneumonia diagnosed?

Answer 16

CXR: May be normal, interstitial infiltrates, reticulonodular markings
BAL and immunofluorescence +- PCR

Question 17

What is the treatment and prophylaxis for pneumocystis pneumonia?

Answer 17

Rx- High dose co-trimoxazole (+- steroid)

Proph: Low dose co-trimoxazole

Question 18

What tuberculosis infections/conditions are more common in HIV+ than HIV- individuals?

Answer 18

Symptomatic primary infection
Reactivation of latent TB
Lymphadenopathies
Miliary TB
Extrapulmonary TB
Multi-drug resistant TB
Immune reconstitution syndrome

Question 19

What organism causes cerebral toxoplasmosis?

Answer 19

Toxoplasma gondii

Question 20

What happens in cerebral toxoplasmosis?

Answer 20

Reactivation of latent infection

Multiple cerebral abscess (chorioretinitis)

Question 21

What are the symptoms/signs in cerebral toxoplasmosis?

Answer 21

Headache
Fever
Focal neurology
Seizures
Reduced consciousness
Raised intracranial pressure

Question 22

What does CMV cause?

Answer 22

Retinitis, colitis, oesophagitis

Question 23

How does CMV present?

Answer 23

Reduced visual acuity
Floaters
Abdo pain
Diarrhoea
PR bleeding

Question 24

What skin infections can be due to HIV?

Answer 24

Herpes Zoster: Multidermatomal, Recurrent
Herpes Simplex: Extensive, Hypertrophic, Aciclovir resistant
Human papilloma virus: Extensive, Recalcitrant, Dysplastic
Penicilliosis
Histoplasmosis

Question 25

What causes HIV-associated neurocognitive impairment?

Answer 25

HIV-1

Question 26

How does HIV-associated neurocognitive impairment present?

Answer 26

Reduced STM | +- motor dysfunction

Question 27

What causes progressive multifocal leukoencephalopathy?

Answer 27

JC virus | Reactivation of latent infection

Question 28

How does progressive multifocal leukoencephalopathy present?

Answer 28

Rapidly progressing Focal neurology Confusion Personality change

Question 29

What are some other neurological presentations of HIV?

Answer 29

``` Distal sensory polyneuropathy Mononeuritis multiplex Vacuolar myelopathy Aseptic meningitis Guillan-Barre syndrome Viral meningitis (CMV, HSV) Cryptococcal meningitis Neurosyphilis ```

Question 30

What causes HIV-associated wasting aka Slim's Disease?

Answer 30

Metabolic (chronic immune activation) Anorexia (multifactorial) Malabsorption/diarrhoea Hypogonadism

Question 31

What causes Kaposi's sarcoma?

Answer 31

Human herpes virus 8 (HHV8)

Question 32

What is the basic pathology of Kaposi's sarcoma?

Answer 32

Vascular tumour

Question 33

How does Kaposi's sarcoma present?

Answer 33

Cutaneous Mucosal Visceral- pulmonary, GI

Question 34

What is the treatment for Kaposi's sarcoma?

Answer 34

HAART Local therapies Systemic chemotherapy

Question 35

What causes Non-Hodgkins lymphoma?

Answer 35

EBV (Burkitt’s lymphoma, primary CNS lymphoma)

Question 36

How does Non-Hodgkins lymphoma present?

Answer 36

``` More advanced B symptoms Bone marrow involvement Extranodal disease Increased CNS involvement ```

Question 37

What should be offered to all with complicated HPV disease?

Answer 37

HIV testing

Question 38

How can cervical cancer present?

Answer 38

Recalcitrant warts | High grade CIN, VIN, AIN, PIN

Question 39

What are the clinical features of non-OI symptomatic HIV?

Answer 39

``` Mucosal candidiasis Seborrhoeic dermatitis Diarrhoea Fatigue Worsening psoriasis Lymphadenopathy Parotitis Epidemiologically linked conditions: STIs, Hepatitis B, Hepatitis C ```

Question 40

What are some haematologic manifestations of HIV?

Answer 40

Anaemia | Thrombocytopenia

Question 41

What are the modes of transmission of HIV?

Answer 41

Sexual Parenteral Mother to Child

Question 42

What factors increase transmission risk of HIV in sex?

Answer 42

Anoreceptive sex Trauma Genital ulceration Concurrent STI

Question 43

How does parenteral transmission of HIV occur?

Answer 43

Injection drug use (sharing 'works') Infected blood products Iatrogenic

Question 44

How does MTCT of HIV occur?

Answer 44

In utero/trans-placental Delivery Breast-feeding

Question 45

What is the sex ratio of HIV?

Answer 45

2.1:1 M:F

Question 46

What risk group has the highest proportion of HIV in the UK?

Answer 46

MSM

Question 47

What services include an opt-out HIV test?

Answer 47

``` TOP services GUM Drug dependency services Antenatal services Assisted conception services ```

Question 48

What high risk groups should regular HIV screening be carried out on?

Answer 48

``` MSM Female partners of bisexual men IVDU Partners of people living with HIV Adults, children, sexual partners, and people with history of iatrogenic exposure from/in an endemic area ```

Question 49

What are the high prevalence areas of HIV?

Answer 49

Sub-Saharan Africa Caribbean Thailand

Question 50

When HIV falls within the DDx what should be performed regardless of risk factors?

Answer 50

HIV test | Risk assessment not necessary

Question 51

What is important when taking an HIV test of an incapacitated person?

Answer 51

Only test if in patients best interest Consent from relative not required If safe, wait until patient regains capacity Obtain support from HIV team if required

Question 52

Which markers of HIV are used by labs to detect infection?

Answer 52

``` RNA (viral genome) Envelope proteins (gp120) Capsule protein (p24) ```

Question 53

What do 3rd generation HIV tests detect?

Answer 53

HIV 1+2 antibody IgM IgG

Question 54

What is the window period of 3rd generation HIV tests?

Answer 54

Avg. 20-25 days

Question 55

What do 4th generation HIV tests detect?

Answer 55

Combined antibody and antigen (p24)

Question 56

What is the window period of 4th generation HIV tests?

Answer 56

14-28 days

Question 57

What is the recent infection testing algorithm?

Answer 57

Can be used to identify if an infection occurred within the preceding 4-6months

Question 58

How does RITA work?

Answer 58

Measure different types of antibodies or strength of antibody binding- HIV1, subtype B

Question 59

What are the targets for anti-retroviral drugs?

Answer 59

``` Reverse transcriptase Integrase Protease Entry: fusion, CCR5 receptor Maturation ```

Question 60

What was shown to have in vitro activity against HIV?

Answer 60

Nucleotide analogues reverse transcriptase inhibitors (NRTI) e.g. zidovudine

Question 61

What is highly active anti-retroviral therapy (HAART)?

Answer 61

A combination of three drugs from at least 2 drug classes to which the virus is susceptible

Question 62

What is most important in preventing drug resistance in HIV?

Answer 62

Adherence

Question 63

What are the S/Es of HAART?

Answer 63

GI S/Es (protease inhibitors), transaminitis, fulminant hep (nevirapine, most others) Skin: rash, HS, SJS (abacavir, nevirapine) CNS: mood, psychosis (efavirenz) Renal: proximal renal tubulopathies (tenofovir, atazanavir) Bone: osteomalacia (tenofovir) CVS: increased MI risk (abacavir, lopinavir, maraviroc) Haematology: anaemia (zidovudine)

Question 64

What enzymes do protease inhibitors interact with?

Answer 64

Liver enzyme inhibitors

Question 65

What enzymes do NNRTIs interact act with?

Answer 65

Liver enzyme inducers

Question 66

Describe partner notification and disclosure in HIV

Answer 66

Voluntary process- may takes weeks, months, years | Duty of care to a known third party

Question 67

How can you prevent onward HIV sexual transmission?

Answer 67

``` Condom use HIV treatment STI screening and treatment Sero-adaptive sexual behaviours Disclosure Post-exposure prophylaxis Pre-exposure prophylaxis ```

Question 68

What are conception options for an HIV+ male, HIV- female?

Answer 68

Timed unprotected sex with HAART | Treatment as Prevention

Question 69

What are conception options for an HIV+ female, HIV-male?

Answer 69

? Self-insemination Timed unprotected sex with HAART Treatment as Prevention

Question 70

How can you prevent mother to child transmission?

Answer 70

``` HAART during pregnancy Vaginal delivery if undetected viral load Caesarean section if detected viral load 4/52 PEP for neonate Exclusive formula feeding ```