HIV 2 Flashcards
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
Why is HIV incidence decreasing?
Earlier diagnosis/ treatment including PEP
PreP
When do we classify HIV as late diagnosis?
If diagnosed when CD4 <350
HIV positive mother.
What is transmission rate of HIV inutero/ via breast milk?
25% transmission in utero
15% transmission via breast milk
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
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
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
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
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
New HIV pregnancy.
What are treatment options for mother?
Tenofovir/ emtricitabine/ atazanavir/ ritonavir
or
Abacavir/ lamivudine/ atazanavir/ efavirenz
If VL >100000 third agent is raltegravir
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
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
KS caused by HHV8
What is treatment?
Minimal lesions - start ART
Intra-lesional chemotherapy if large lesion
Systemic doxorubicin if disseminated disease
What are oral symptoms of aadvanced HIV?
oral candidiasis cold sores - HSV1 oral hairy leukoplakia necrotising gingivitis/ periodonitis KS - HHV8 oral lymphoma
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
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
Which ART have excellent CSF penetration?
Zidovudine
Dolutegravir
Nevirapine
Which ART drugs have poor CSF penetration?
Tenofovir
Enfuvirtide
Most other drugs have reasonable penetration
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
