HIV 2 Flashcards by B M

What is incidence/ prevalence of HIV in UK?

5000/ year new diagnosis

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

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Why is HIV incidence decreasing?

Earlier diagnosis/ treatment including PEP

PreP

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When do we classify HIV as late diagnosis?

If diagnosed when CD4 <350

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HIV positive mother.

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

25% transmission in utero

15% transmission via breast milk

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

How much does ART reduce risk transmission?

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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Which ART drugs are safe pregnancy?

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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What are risks of using dolutegravir in pregnancy?

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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Maternal HIV new diagnosis, when to check viral load?

When to check CD4 count?

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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New diagnosis HIV in pregnancy.

When is it recommended to start treatment?

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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New HIV pregnancy.

What are treatment options for mother?

Tenofovir/ emtricitabine/ atazanavir/ ritonavir

Abacavir/ lamivudine/ atazanavir/ efavirenz

If VL >100000 third agent is raltegravir

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Possible HIV infected neonate.

What blood tests are required?

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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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

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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KS caused by HHV8

What is treatment?

Minimal lesions - start ART

Intra-lesional chemotherapy if large lesion

Systemic doxorubicin if disseminated disease

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What are oral symptoms of aadvanced HIV?

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

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

Non-infectious/ infectious

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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What is HIV viral escape?

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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Which ART have excellent CSF penetration?

Zidovudine

Dolutegravir

Nevirapine

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Which ART drugs have poor CSF penetration?

Tenofovir

Enfuvirtide

Most other drugs have reasonable penetration

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Which ARVs are cytochrome p450 inducers?

Atazanvir
Darunavir
Ritonavir
Cobicistat

Efavirenz
Nevirapine

What is association between PI and corticosteroids?

Includes inhaled steroids

Not recommended as PI inhibit steroid metabolism, by inhibiting CYP3A4

Beclomethasone is safest

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

Clopidogrel/ ticagrelor and ritonavir

Dabigatran and cobicistat

Warfarin - variable levels with multiple ARVs

Why does doultegravir/ ritonavir/ cobicistat increase creatinine levels?

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

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

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

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

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

When to consider HIV2 infection? HIV2 RNA testing performed in Birmingham

West African Atypical serological results CD4 decline if undetectable HIV1 RNA

What drugs is HIV2 intrinsically resistant to?

all NNRTIs Fusion inhibitor - enfuvirtide

HIV2 Little studies about when to start treatment, so start as soon as possible to prevent disease transmission What are initial treatment regimens?

Two NRTIs + INT Two NRTIs + PI e.g Tenofovir/ emtricitabine/ dolutegravir Tenofovir/ emtricitabine/ darunavir abacavir/ lamivudine/ dolutegravir

When to perform HIV resistance testing? Assay checks point mutations using NGS

New diagnosis - baseline Pregnancy Treatment failure - if suspect drug resistance

What is process of NGS identifying resistance in HIV?

Extract nucleic acid RT and PCR Sequence genes using overlapping primers Generate data compare to database of known resistance mutations

Why does HIV persist without eradication?

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

What are differences between these drugs? Tenofovir disoproxil TDF Tenofovir alafenamide TAF

TAF - longer plasma half life, and more stable in plasma. Less nephrotoxicity – reduced creatinine reabsorption Less bone disease Safe first trimester

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?

Tenofovir alafenamide TAF Emtricitabine Bictegravir (not available on its own)

New medication Doravirine is a NNRTI. What are its benefit?

Less susceptible resistance compared to other NNRTI No interaction PPI Less site effects e.g diarrhoea, headache

New long acting injection forms are available Initial treatment to get patient undetectable VL. What drugs can be given?

carbotegravir and rilpivirine Give IM, every month

What are examples of entry and fusion inhibitors? What receptors do they block?

Inhibitors of entry - - Marviroc binds CCR5 - need check tropism - Ibalizumab binds CD4 (post-attachment inhibitor) - Fostemsavir binds gp120 attachment inhibitor Fusion - Enfuvirtide

New treatments may include neutralising monoclonal antibodies. What are examples of how do they work?

Bind to CD4 binding site, inhibiting fusion Bind to V3 loop of gp120, inhibiting fusion

HIV Ag/Ab combo test on Architect What are the targets?

p24 antigen gp41 antibody HIV1 gp36 HIV2

HIV PEP Truvada + Raltegravir What are common side effects?

``` 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

HIV PEP truvada and raltegravir Patient experiencing side effects of of these drugs or has poor renal function What are other options for PEP?

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

Why is loperamide often prescribed with PEP?

NRTI/ INT can both cause diarrhoea if having to switch to PI - this has even higher risk of diarrhoea

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

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

What new drug is available as an injectable?

Cabotegravir/ Rilpivirine combination injection tablets or injection Integrase inhibitor/ NNRTI Only if HIV VL undetectable, and known to have no NNRTI mutations

Cabotegravir/ rilpivirine injections What is dosing schedule?

injection once a month each drug into a different gluteal muscle

Cabotegravir/ rilpivirine injections What groups should we be cautious of using in?

Do not use if known NNRTI mutation Do not use if detectable VL Caution if high BMI

Mutations documentation What does the mutation mean: K65R

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

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

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