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Medical Microbiology and Virology > HIV 2 > Flashcards

HIV 2 Flashcards

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1
Q

What is incidence/ prevalence of HIV in UK?

A

5000/ year new diagnosis

100 000 HIV patients in UK
50% gay
25% Black African
25% heterosexual white
IVDU minimal
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2
Q

Why is HIV incidence decreasing?

A

Earlier diagnosis/ treatment including PEP

PreP

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3
Q

When do we classify HIV as late diagnosis?

A

If diagnosed when CD4 <350

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4
Q

HIV positive mother.

What is transmission rate of HIV inutero/ via breast milk?

A

25% transmission in utero

15% transmission via breast milk

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5
Q

How much does C-section reduce rate of HIV transmission in pregnancy?

How much does ART reduce risk transmission?

A

C-section reduces rate from 25% to 12%

ART reduces to <1% transmission. Longer duration of cART lower risk of transmission

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6
Q

Which ART drugs are safe pregnancy?

A 
Abacavir
Emtricitabine
Lamivudine
Tenofovir TDF - safe
Tenofovir TAF - 2nd/3rd trimester
Zidovudine

Efavirenza
NEvirapine
Rilpivirine

Atazanavir
Darunavir
Lopinavir
Ritonavir

Raltegravir
Dolutegravir not safe
Elvitegravir not enough data

Almost all common drugs are safe

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7
Q

What are risks of using dolutegravir in pregnancy?

A

1 in 2000 neural tube defect

Give extra folic acid

Neural tube closes at 6 weeks, so if presents after 6 weeks, then no need to switch

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8
Q

Maternal HIV new diagnosis, when to check viral load?

When to check CD4 count?

A

Viral load:

  • baseline
  • 4 weeks
  • one every trimester
  • 36 weeks - will determine mode of delivery*
  • at delivery

CD4

  • baseline
  • delivery

*if VL <50/ml can have normal vaginal delivery

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9
Q

New diagnosis HIV in pregnancy.

When is it recommended to start treatment?

A

Start at beginning of second trimester

If CD4 count <200 or VL >100000, start in first trimester, as need more time to bing down VL

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10
Q

New HIV pregnancy.

What are treatment options for mother?

A

Tenofovir/ emtricitabine/ atazanavir/ ritonavir

or

Abacavir/ lamivudine/ atazanavir/ efavirenz

If VL >100000 third agent is raltegravir

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11
Q

Possible HIV infected neonate.

What blood tests are required?

A 
baseline - proviral DNA
2 weeks - proviral DNA - only if high risk
6 weeks - proviral DNA
12 weeks - proviral DNA
22-24 months - HIV Ab

If proviral DNA is positive, start prophylactic co-trimoxazole and refer for assessment

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12
Q

Neonate at risk of HIV.

What is prophylaxis for newborn?

Very low risk - mum on ART with undetectable VL on two occassions

Low risk - mum on ART (less than 10 weeks), undetectable VL on one sample

high risk - if risk maternal VL is >50 at time of delivery

A

Very low risk
oral zidovudine 4mg/kg bd 2 weeks

Low risk
oral zidovudine 4mg/kg bd 4 weeks

High risk
oral zidovidine/ lamivudine/ nevirapine
4 weeks

If unable to tolerate oral, zidovudine is only drug available IV

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13
Q

KS caused by HHV8

What is treatment?

A

Minimal lesions - start ART

Intra-lesional chemotherapy if large lesion

Systemic doxorubicin if disseminated disease

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14
Q

What are oral symptoms of aadvanced HIV?

A 
oral candidiasis
cold sores - HSV1
oral hairy leukoplakia
necrotising gingivitis/ periodonitis
KS - HHV8
oral lymphoma
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15
Q

HIV patient with abnormality of CT head, what is differential diagnosis?

Non-infectious/ infectious

A 
Non-infectious -
CNS tumours
primary CNS lymphoma
IRIS 
Vascular disease - increased risk in HIV

Infectious -
bacterial abscess
tuberculosis
neurosyphilis

CMV
PML

toxoplasmosis
cryptococcosis

candida
aspergillus

If treat infectious cause e.g toxoplasma, CNS lesion can initially increase in size due to IRIS

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16
Q

What is HIV viral escape?

A

HIV can hide in sacntuary site e.g brain/ CSF

ART usually has good penetration to CNS. If it does not get good penetration, HIV can replicate in CSF, and then escpae into blood stream, giving detectable viral load

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17
Q

Which ART have excellent CSF penetration?

A

Zidovudine

Dolutegravir

Nevirapine

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18
Q

Which ART drugs have poor CSF penetration?

A

Tenofovir

Enfuvirtide

Most other drugs have reasonable penetration

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19
Q

Which ARVs are cytochrome p450 inducers?

A

Atazanvir
Darunavir
Ritonavir
Cobicistat

Efavirenz
Nevirapine

20
Q

What is association between PI and corticosteroids?

Includes inhaled steroids

A

Not recommended as PI inhibit steroid metabolism, by inhibiting CYP3A4

Beclomethasone is safest

21
Q

Which anti-coagulants/ platelets can have interactions with ART?

A

Clopidogrel/ ticagrelor and ritonavir

Dabigatran and cobicistat

Warfarin - variable levels with multiple ARVs

22
Q

Why does doultegravir/ ritonavir/ cobicistat increase creatinine levels?

A

Affects transporters involved in renal clearance. So no damage to kidneys, but reduced creatinine clearance

23
Q

Host has restriction factors which are cellular proteins to inhibit virus replication. IFN increases levels of these proteins

What is role of:

TRIM5-alpha

SAMHD1

A

TRIM5-alpha - cytoplasmic protein targets viral capsid proteins with proteasome causing destruction

SAMHD1 - cytoplasmic enzyme hydrolyses dNTPs (deoxyribonucleotide) reducing pool available for replication

HIV2 more sensitive to TRIMalpha than HIV1

24
Q

Host has restriction factors which are cellular proteins to inhibit virus replication.
IFN increases levels of these proteins

What is role of:

APOBEC3

Tetherin interferon-inducible surface protein

A

APOBEC3 - cytosine deaminase incorporated into budding virion upon viral entry, inhibits RT/ INT

Tetherin interferon-inducible surface protein - prevents enveloped virions from detaching from cell surface

25
Q

When to consider HIV2 infection?

HIV2 RNA testing performed in Birmingham

A

West African
Atypical serological results
CD4 decline if undetectable HIV1 RNA

26
Q

What drugs is HIV2 intrinsically resistant to?

A

all NNRTIs

Fusion inhibitor - enfuvirtide

27
Q

HIV2

Little studies about when to start treatment, so start as soon as possible to prevent disease transmission

What are initial treatment regimens?

A

Two NRTIs + INT

Two NRTIs + PI

e.g

Tenofovir/ emtricitabine/ dolutegravir

Tenofovir/ emtricitabine/ darunavir

abacavir/ lamivudine/ dolutegravir

28
Q

When to perform HIV resistance testing?

Assay checks point mutations using NGS

A

New diagnosis - baseline

Pregnancy

Treatment failure - if suspect drug resistance

29
Q

What is process of NGS identifying resistance in HIV?

A

Extract nucleic acid

RT and PCR

Sequence genes using overlapping primers

Generate data compare to database of known resistance mutations

30
Q

Why does HIV persist without eradication?

A

DNA incorporated into reservoir of memory B cells, which can live for 50-70 years

“Berlin patient” had HIV, and developed AML. Had extensive chemo/radiotherapy, and bone marrow transplant. No HIV found in blood/ tissues

31
Q

What are differences between these drugs?

Tenofovir disoproxil TDF

Tenofovir alafenamide TAF

A

TAF -

longer plasma half life, and more stable in plasma.

Less nephrotoxicity – reduced creatinine reabsorption

Less bone disease

Safe first trimester

32
Q

New medication Biktarvy is suitable as less renal disease, less bone disease, suitable for pregnancy. Good results, with little side effects

What drugs does it include?

A

Tenofovir alafenamide TAF

Emtricitabine

Bictegravir (not available on its own)

33
Q

New medication Doravirine is a NNRTI.

What are its benefit?

A

Less susceptible resistance compared to other NNRTI

No interaction PPI

Less site effects e.g diarrhoea, headache

34
Q

New long acting injection forms are available

Initial treatment to get patient undetectable VL.

What drugs can be given?

A

carbotegravir and rilpivirine

Give IM, every month

35
Q

What are examples of entry and fusion inhibitors?

What receptors do they block?

A

Inhibitors of entry -

  • Marviroc binds CCR5 - need check tropism
  • Ibalizumab binds CD4 (post-attachment inhibitor)
  • Fostemsavir binds gp120 attachment inhibitor

Fusion
- Enfuvirtide

36
Q

New treatments may include neutralising monoclonal antibodies.

What are examples of how do they work?

A

Bind to CD4 binding site, inhibiting fusion

Bind to V3 loop of gp120, inhibiting fusion

37
Q

HIV Ag/Ab combo test on Architect

What are the targets?

A

p24 antigen

gp41 antibody HIV1
gp36 HIV2

38
Q

HIV PEP

Truvada + Raltegravir

What are common side effects?

A 
The most common side-effects were 
fatigue (37%)
diarrhoea (25%)
nausea (24%)
flatulence (24%)
abdominal cramps (21%)
bloating (16%)
headache (15%)
vivid dreams (15%)
depression (10%)
thirst (10%).

Raltegravir can often cause a hypersensitivity reaction e.g rash/ fever

39
Q

HIV PEP truvada and raltegravir

Patient experiencing side effects of of these drugs or
has poor renal function

What are other options for PEP?

A

Replace NRTI backbone with -
Lamivudine 150mg BD
Zidovudine 250mg BD

Replace INT with INT -
Dolutegravir

Replace INT with PI -
Lopinavir/ ritonavir (kaletra)
Darunavir/ ritonavir
Atazanavir/ ritonavir

40
Q

Why is loperamide often prescribed with PEP?

A

NRTI/ INT can both cause diarrhoea

if having to switch to PI - this has even higher risk of diarrhoea

41
Q

Patient has positive HIV Ag/Ab test. CD4 count is low
But undetectable viral load.

What are explanations?

A

Problem with test -

  • pre-analytical - wrong patient sampled
  • false positive Ag/Ab test
  • other cause for CD4 lymphopenia
  • HIV1 with rare group (N, O, P) or recombinant circulating form not detected by current viral load assay
  • HIV1 with elite controller status

Other -
- HIV2 positive, needs RNA VL sent to Birmingham

42
Q

What new drug is available as an injectable?

A

Cabotegravir/ Rilpivirine combination injection

tablets or injection

Integrase inhibitor/ NNRTI

Only if HIV VL undetectable, and known to have no NNRTI mutations

43
Q

Cabotegravir/ rilpivirine injections

What is dosing schedule?

A

injection once a month

each drug into a different gluteal muscle

44
Q

Cabotegravir/ rilpivirine injections

What groups should we be cautious of using in?

A

Do not use if known NNRTI mutation

Do not use if detectable VL

Caution if high BMI

45
Q

Mutations documentation

What does the mutation mean: K65R

A

K - amino acid wild-type. K is abbreviation of Lysine

65 - amino acid position

R - amino acid substitution conferring resistance. R is abbreviation or arginine

46
Q

With HIV diagnostics, what is meant by the eclipse period, and window period

A

Eclipse period - early infection in which virus cannot be readily obtained from the host. e.g a viral load may be negative

Window period - time until first detection of a marker. e,g p24 or antibody

Medical Microbiology and Virology (60 decks)

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