HIV post exposure prophylaxis (PEP) Flashcards
What are the 3 broad categories through which HIV exposure may occur?
1) Occupational exposure
2) Community non-occupational exposure
3) Sexual exposure
How long does it take for HIV to start to replicate once it has crossed the mucosal barrier?
Up to FORTY EIGHT (48) hours
When is HIV first detected in the blood?
FIVE (5) days
Within what time frame has PEP been shown to reduce dissemination and replication of HIV virus?
start within SEVENTY TWO (72) hours
UK surveillance data of occupational exposure to HIV - summarise
Since 2004 all occupational exposures started on PEP have no new cases HIV
Brazil study that support PEPSE use - summarise
MSM in Brazil
Overall HIV incidence similar to expected
PEP group less seroconversion than non-PEP group
What were the percentages for seroconversion for the PEP group vs non PEP group in the PEP Brazil study?
1.4% vs 7.5%
PEP vs nonpep
Describe the EXPLORE study for PEPSE?
MSM in USA
behavioural intervention trial
No difference HIV seroconversion between PEP vs nonPEP group
What data is there to support PEP in exposure through PWID?
LIMITED data
What are the 4 reasons for PEPSE failing?
1) DELAYED ART start
2) POOR or non- adherence
3) Further HIGH-RISK SEX after PEP stops
4) Early PRIMARY HIV INFECTION already established
For PEPSE, what was the adherence to single tablet regimen vs twice daily?
71% TDF/FTC/EVG/r vs
57% RAL based (BD) or
39% PI based (BD)
When was the last recorded occupational HIV transmission?
1999
What 3 factors contribute to the risk of HIV transmission through sexual exposure?
1) TYPE of sex
2) HIV viral load of INDEX partner
3) SUSCEPTIBILITY of recipient if partner not virologically suppressed ie concomitant STI/GENITAL ULCER DISEASE
HPTN 052 trial - describe what this trial was?
Randomised control trial (RCT)
Heterosexual serodiscordant couples
HPTN 052 trial - what were the outcomes?
8 linked transmissions
- 4 prior to full viral suppression
- 4 related to treatment failure/detectable VL
- None if VL undetectable
PARTNER trial - describe what this trial was?
- Europe
- Prospective observational
- Gay and HETEROSEXUAL, discordant couples
PARTNER trial - what were the outcomes?
888 couples
No linked transmissions
PARTNER 2 - describe this trial?
- Extension of PARTNER to improve understanding of transmission risk for MSM
- Prospective observational
- MSM
PARTNER 2 - what were the outcomes?
782 couples
No linked transmissions
OPPOSITES ATTRACT - describe this trial
Small observational
MSM
OPPOSITES ATTRACT - what were the outcomes?
232 couples
No linked transmission
What FOUR trials support the statement U=U?
HPTN 052
PARTNER
PARTNER 2
OPPOSITES ATTRACT
What is the estimated prevalence of DETECTABLE HIV viraemia in England for MSM?
23/1000
What is the estimated prevalence of DETECTABLE HIV viraemia in England for PWID?
6.7/1000
Is the estimated prevalence of DETECTABLE HIV viraemia for PWID higher for men or women?
WOMEN
11 per 1000 vs 5 per 1000
estimated prevalence of DETECTABLE HIV viraemia in heterosexual non-Black African MEN?
Very low
0.2 per 1000
estimated prevalence of DETECTABLE HIV viraemia in heterosexual non-Black African WOMEN?
Very low
0.1 per 1000
Is the estimated prevalence of DETECTABLE HIV viraemia for Black Africans higher for men or women?
WOMEN
8.7 per 1000 vs 5.8 per 1000
What is the risk of HIV transmission with RECEPTIVE anal sex + EJACULATION?
1 in 65
What is the risk of HIV transmission with RECEPTIVE anal sex + no ejaculation?
1 in 170
What is the risk of HIV transmission with INSERTIVE anal sex + CIRCUMCISION?
1 in 909
What is the risk of HIV transmission with INSERTIVE anal sex + no circumcision?
1 in 161
Which specific exposures involving anal sex have very similar risks?
Receptive + no ejaculation
(1 in 170)
Insertive + no circumcision
(1 in 161)
What is the risk of HIV transmission with RECEPTIVE vaginal sex?
1 in 1000
What is the risk of HIV transmission with INSERTIVE vaginal sex?
1 in 1219
Which is highest risk, receptive or insertive VAGINAL sex?
Receptive
1 in 1000 vs 1 in 1219
What TWO exposure types have risk of HIV transmission 1 in 1000?
receptive vaginal
mucocutaneous
What is the risk of HIV transmission with SEMEN SPLASH into eye?
<1 in 10000
What is the risk of HIV transmission with ORAL sex?
< 1 in 10 000
What is the risk of HIV transmission with a human BITE?
< 1 in 10 000
What is the risk of HIV transmission with blood TRANSFUSION?
1 in 1 (ie 100%)
What is the risk of HIV transmission with NEEDLESTICK injury?
1 in 333
What is the risk of HIV transmission with sharing injecting equipment inc chemsex?
1 in 149
What THREE exposure types have risk of HIV transmission <1 in 10 000?
SEMEN SPLASH to eye
ORAL sex
Human BITE
How do you calculate risk of HIV transmission?
Risk of HIV transmission =
Risk per type of EXPOSURE x risk that source is HIV positive with detectable viral load (ie population)
What FIVE factors in the index case increase the risk of HIV transmission if NOT on ART?
1) High VL
2) Breaches of mucosal barrier
3) Menstruation
4) Pregnancy/post partum
5) STI or genital ulcer disease
If the index case has a detectable viral load what impact does this have on the risk of HIV transmission?
2.9 fold increase per act with each log10 increase
Through what THREE scenarios might an occupational exposure occur?
Contact with bodily fluids or tissue
1) PERCUTANEOUS
2) MUCOUS MEMBRANE (or non-intact skin)
3) BITE
Which Body fluids are implicated in the transmission of HIV?
Blood, semen, vaginal secretions
CSF
Synovial, pleural, peritoneal, pericardial or amniotic fluid
Which Body fluids are NOT implicated in the transmission of HIV?
faeces, nasal secretions, saliva, gastric secretions, sputum, sweat, tears, urine or vomit.
In which situation might there be a risk of HIV transmission in the bodily fluids not typically implicated in infection?
If there is blood in them
What FOUR factors increase the risk of HIV seroconversion in the event of percutaneous injury?
1) DEEP injury
2) VISIBLE BLOOD on device
3) Needle in VEIN or ARTERY
4) AIDS in index case
What is the risk of HIV transmission through non-intact skin?
Negligible
Have there been any reported cases of HIV transmission through non-intact skin?
No
What is the risk of HIV transmission through SPITTING and BITING?
Spitting - NO risk
Biting - NEGLIGIBLE (increased if blood in saliva and high VL index case)
What factors have been present when HIV transmission occurred through a bite?
Index case: HIGH viral load, BLOOD in mouth and DEEP or MULTIPLE bites
HIV outbreak in PWID in Glasgow - describe
Identified 2015 Ongoing HIV prevalence increased 0.1% to 4.8% overall 1.1% to 10.8% Glasgow city centre
What are the THREE main drugs used in chemise?
1) crystal methamphetamine
2) GHB/GBL
3) ephedrine
What is the reason for taking ‘chems’?
SUSTAIN or ENHANCE the experience of sex
What is an alternative term for ‘injecting’ drugs in the context of chemsex?
‘slamming’
What proportion of MSM partake in chemsex?
17%
What proportion of MSM partaking in chemsex, inject drugs?
10%
There are FOUR categories of PEP recommendation - what are they?
RECOMMENDED
CONSIDER
GENERALLY NOT recommended
NOT RECOMMENDED
What is the definition of ‘PEP RECOMMENDED’?
Benefits of PEP outweigh risk
PEP should be given unless clear reason not to
What is the definition of ‘CONSIDER PEP’?
RISK of HIV transmission LOW
Risk vs benefit balance less clear
requires CASE by CASE assessment
What is the definition of ‘PEP GENERALLY NOT RECOMMENDED’?
risk of HIV transmission VERY LOW
potential TOXICITY of PEP likely outweighs benefit
PEP will very rarely be given
What is the definition of ‘PEP NOT RECOMMENDED’?
NEGLIGIBLE risk of HIV
PEP should NOT be given
What information is important to get from the index case of a potential HIV transmission?
HIV status
Viral load
ART - on or off
Past virological failure or resistance
If the index case is known to be HIV positive with detectable VL what is the calculation used to establish risk of transmission?
1 x risk per exposure
ie Risk of HIV transmission = risk that source is HIV positive with a detectable HIV viral load X risk per exposure
What study types support U=U with regards to sexual exposure?
RCT
Observational studies
What THREE factors in the PLWHIV need to be met to guarantee U=U?
1) UNDETECTABLE VL
2) ART SIX (6) months
3) Good ADHERENCE
Is PEP recommended for oral sex with ejaculation?
NO
What is the risk of HIV transmission for oral sex with ejaculation?
<1/10 000
What factors may increase the risk of HIV transmission for oral sex?
Recent dental procedures
Pharyngitis
Chemotherapy
Periodontal disease
In what extreme circumstances can PEP be considered for oral sex?
1) PRIMARY HIV INFECTION of index
2) oropharyngeal TRAUMA/ULCERATION
Is PEP for sexual assault generally recommended in the UK?
NO
In what situation might PEP be more readily considered in event of sexual assault?
Assailant is from HIGH PREVALENCE group
What is the prevalence of HIV in female sex workers in WESTERN EUROPE?
<1%
What is the prevalence of HIV in female sex workers in CENTRAL EUROPE?
1-2%
What is the prevalence of HIV in female sex workers in EASTERN EUROPE?
2-8%
What lifestyle factor increases prevalence of HIV In female sex workers?
INJECTING DRUG USERS
What is the prevalence of HIV in MALE sex workers?
14%
What is the evidence to support U=U in context of percutaneous injury?
There is none
When considering PEP for a percutaneous injury and index case with HIV, what information should be given to the patient?
- Highly likely viral suppression (undetectable) eliminates the risk of HIV transmission
- Lack of evidence to fully support
Should PEP be recommended in a community needlestick exposure?
NO
What is the summary of risk of HIV transmission from a community needlestick exposure?
Extremely low risk
Has there ever been a reported case of HIV transmission from a community needlestick exposure?
No
How do you calculate the maximum potential risk of HIV transmission from a community needlestick exposure? And in what setting only should it be used?
Risk of HIV transmission
= risk that source is HIV positive with a detectable viral load X
0.3 (risk per exposure)
Only use if recipient is confident freshly discarded needle
How quickly does HIV become non-viable in dried blood?
TWO (2) hours
In what situation ONLY would PEP be considered for a bite injury?
Biter: 1) SALIVA visibly contaminated with BLOOD 2) known DETECTABLE viral load Injury: 3) SEVERE or DEEP
What specific information is important to get from index case who are PWID?
CURRENT injecting
SHARING equipment
What is the recommended regimen for PEP?
Tenofovir disoproxil 245mg/emtricitibine 200mg
+
raltegravir 1200mg
What TWO factors may change the PEP regimen?
1) Past or current history of ART FAILURE OR RESISTANCE in index case
2) PREGNANCY
What is the recommended regimen for PEP in PREGNANCY?
Tenofovir disoproxil 245mg/emtricitibine 200mg
+
RALTEGRAVIR 400mg twice daily
If 400mg raltegravir is not available for pregnant person how should the PEP regimen be altered?
Raltegravir 600mg twice daily
Switch to 400mg as soon as available
Why is tenofovir disoproxil based regimens preferred over zidovudine?
Higher completion rates
Less adverse events causing discontinuation of PEP
When would tenofovir alafenamide (TAF) be used instead of TDF for PEP?
Chronic kidney disease
eGFR <50ml/min
What is the limitation of using TAF in PEP regimen?
No in-human data
What evidence supports the theoretical utility of TAF in a PEP regimen?
PrEP trials (for MSM)
What are the VERY common (>1/10) side effects with TDF/FTC?
Headache,
dizziness,
diarrhoea,
nausea
What are the COMMON (1/10-1/100) side effects with TDF/FTC?
insomnia,
abdominal pain
What is the main risk associated with TDF, other than side effects?
Renal toxicity
What are the concerns about using raltegravir 1200mg once daily for PEP?
More hygroscopic
Must be stored in original moisture protected packaging
Cannot divide pack into start packs
Minimum duration available 30 days
Why is raltegravir preferred integrase inhibitor for PEP?
1) SAFE in pregnancy
2) COST
3) good TOLERABILITY
What are the most common side effects when using integrase inhibitors for PEP?
diarrhoea
nausea
headache
If using dolutegravir for PEP what side effect should be considered and risk assessed for?
CNS effect resulting in
SUICIDAL ideation or behaviour
In a study in Belfast assessing tolerability of RAL in PEP, what proportion experience side effects?
13%
What is the limiting factor for use of elvitegravir/cobicistat in PEP?
Drug-drug INTERACTION with cobicistat
What is a potentially useful aspect of elvitegravir/cobicistat for use as PEP?
Can be used with TDF/FTC as SINGLE TABLET regimen
1 seroconversion occurred in a study looking at TDF/FTC/EVG/c as PEP, what was this attributed to?
MULTIPLE EXPOSURES before and after PEP initiation
What is the limiting factor for use of dolutegravir in PEP?
Risk of NEURAL TUBE DEFECT in PREGNANCY
Instead of integrase inhibitors what else can be used as 3rd agent for PEP?
Protease inhibitors
What PROTEASE INHIBITORS can be used in PEP?
DARUNAVIR/ritonavir
or
ATAZANAVIR/ritonavir
What pharmacokinetic BOOSTER is used with PI for PEP?
ritonavir
If using TAF/emtricitibine (Descovy) what DOSE is used with INTEGRASE inhibitors?
TAF 25mg/
emtricitibine 200mg
If using TAF/emtricitibine (Descovy) what DOSE is used with PROTEASE inhibitors?
TAF 10mg/
emtricitibine 200mg
SWALLOWING difficulties - TDF/FTC - how to manage?
DISSOLVE in
100ml
WATER or ORANGE juice
SWALLOWING difficulties - LOPINAVIR/RITONAVIR - how to manage?
LIQUID formulation
Which ART is available in liquid form and can be used in PEP?
LOPINAVIR/ritonavir
SWALLOWING difficulties - DOLUTEGRAVIR - how to manage?
SPLIT or CRUSH
add to SEMI-SOLID food
What is the prevalence of NNRTI resistance in the UK?
4.2%
Why are NNRTI not recommended in PEP?
Significant RESISTANCE in UK
Why are protease inhibitors not first line for PEP?
1) DDI (esp risk of recreational drug use in MSM)
2) SIDE EFFECTS
Through what mechanism are PIs implicated in drug-drug interactions?
Cytochrome p450 INHIBITOR
INCREASES drug levels metabolised through same pathway
What FOUR common classes of medication are INCREASED through CYP450 pathway when protease inhibitors are used?
1) CORTICOSTEROIDS
2) RECREATIONAL DRUGS
3) ANTIBIOTICS
4) ANTIPSYCHOTICS
Can MARAVIROC be used as PEP?
under INVESTIGATION
What are the beneficial properties of MARAVIROC that make it potential for use as PEP?
TOLERABILITY
Very high levels GENITAL TRACT
Why is maraviroc not currently recommended as PEP?
1) Potential for non-CCR5-tropic HIV to be transmitted
2) Not currently first line HIV treatment
What mode of action is MARAVIROC in HIV?
CCR5 chemokine receptor INHIBITOR
If a person has previously been unable to complete PEP due to tolerability or toxicity issues what should be offered?
ALTERNATIVE, TAILORED regimen + medication to reduce side effects
What may increase the risk of myopathy or rhabdomyolysis when using integrase inhibitors as PEP?
History of MYOPATHY
Concomitant medications with risk such as STATINS
If antiemetics are required for a protease inhibitor-containing PEP regimen, what ANTIEMETIC should be AVOIDED?
DOMPERIDONE
significant DDI
Which DIVALENT cations bind to raltegravir in the GI tract?
Iron
Magnesium
Calcium
Aluminium
Which THREE groups of drugs should be avoided when taking raltegravir, or carefully spaced?
1) ANTACIDS
2) IRON supplements
3) MULTIVITAMINS
Which ANTIBIOTIC is specifically CONTRAINDICATED with BOOSTED drugs ie PIs and elvitegravir?
RIFAMPICIN
What evidence supports the 72 hour cut off for PEP start?
- Rhesus MONKEY
- Intrarectal SIV inoculum study
- ART started DAY 3 after exposure
- Blocked emergence of viral RNA and proviral DNA in blood, lymph nodes and GI tract
- 24 weeks after stopping ART - VIRAL REBOUND
What is the evidence to support 28 days of PEP?
- Macaques - IV SIV inoculation
- PEP start within 24 hours
- ALL protected with 28 days PEP
- 50% protected with 10 days PEP
- ZERO protected with 3 days PEP
PEP starter packs (5 days) vs 28 day pack - compare?
Low level evidence supports
provision of 28 days at first presentation
- better completion rates
What proportion of ED initiated PEP is for a high risk exposure?
80%
Prior to starting PEP what THIRTEEN points must be discussed with the patient?
1) RATIONALE for PEP
2) LACK of DATA on EFFICACY of PEP
3) START ASAP + importance of ADHERENCE
4) SIDE EFFECTS
5) DDI
6) need for EMERGENCY CONTRACEPTION
7) Symptoms of SEROCONVERSION + urgent medical advice
8) FOLLOW UP
9) HIV TEST
10) 28 DAYS of PEP
11) HIV TEST AT 10.5 WEEKS
12) CONDOMS until fu HIV test post PEP
13) SUPPORT inc MENTAL HEALTH and SOCIAL
Is anxiety an indication for PEP?
No
If a person seeking PEP is experiencing anxiety what can be offered?
1) Risk assessment for PEP (often identifies low risk and reassuring)
2) Psychological support services
What baseline BBV tests should be done on the INDEX case in relation to PEP assessment?
HIV Ag/Ab 4th gen
HBsAg
HCV Ab
(or viral load if HIV +ve)
What BASELINE tests should be done for the RECIPIENT in relation to PEP assessment?
ALL exposures: eGFR ALT HIV Ag/Ab HbsAb, sAg & cAb HCV Ab
SEXUAL exposures: (add)
syphilis
WOMEN of CHILDBEARING potential: (add)
uHCG
What FOLLOW UP tests are required after start of PEP?
ALL exposures: 3 months - HIV Ag/Ab - HBsAb AND sAg - HCV Ab 6 months - HBsAg (if no sAb at 3 months) - HCV Ab SEXUAL exposures: 2 weeks - NAAT for chlamydia/gonorrhoea 3 months - syphilis serology
Are kidney and liver function tests required after starting PEP?
No
Consider if history of renal or liver disease
Why are kidney and liver function tests NOT required after starting PEP?
Renal toxicity REVERSIBLE (PrEP trials)
Low risk of transaminitis with integrase inhibitors
What is the earliest point at which an HIV test can be performed after PEP completion?
45 days (ie 10.5 weeks from PEP start) However more convenient to time in with other 12 week bloods
When should hepatitis B vaccination be offered in setting of PEP assessment?
Unvaccinated or vaccination status unknown
When should hepatitis B immunoglobulin be offered in setting of PEP assessment?
If index case is KNOWN HBsAg POSITIVE
What dosing regimen of hepatitis B vaccination is suggested in setting of PEP assessment?
ULTRA RAPID
0, 7, 21 days and 12 months
Describe ULTRA RAPID regimen for hepatitis B vaccination?
0, 7, 21 days and 12 months
When should hepatitis C core antigen or RNA be checked?
If there has been a significant hepatitis C risk ie needlestick from known HCV +ve
When can hepatitis C core antigen or RNA be checked in context of high risk exposure?
as early as 2 weeks
What should be assessed in women of childbearing age requesting PEP?
Need for EMERGENCY CONTRACEPTION
Chance of current PREGNANCY
What further provision should be offered to people being assessed for PEP who are likely to be at higher risk of HIV acquisition in the future?
Referral to sexual health services for risk reduction
CONDOMS
PREP
BEHAVIOUR CHANGE COUNSELLING
What proportion of PEP recipients had an STI at baseline?
15-17%
What additional proportion of PEP recipients had an STI at 2 weeks post PEP start?
4-5%
At what time should NAAT testing be offered to PEP recipients?
At baseline (to avoid lost to follow up) and if not sexual assault 2 weeks after exposure
If the recipient has HBV chronic infection (sAg +ve) and is started on PEP for HIV exposure, is it safe to stop PEP?
iPREX study showed possible to use TDF/FTC in patients with chronic HBV and able to stop without cirrhosis or hepatic flares (however NEEDS SPECIALIST input)
What is the complication of starting and then stopping TDF/FTC or 3TC in people with chronic HBV infection?
Risk of cirrhosis or hepatic flare
Is there a risk for HBV resistance if PEP is given to a person with HBV infection?
Extremely UNLIKELY, only 4 weeks therapy
If a person is on TDF only to treat HCV infection, do they need to have PEP in the event that they are exposed to HIV?
Unclear
Evidence for TDF as PrEP in heterosexual men and women
Should consider PEP especially if MSM
Pregnant women are at increased risk of HIV transmission, what could the high viraemia of primary HIV Infection lead to?
High likelihood of INTRAUTERINE infection
What resource is used to understand the outcomes for pregnancy exposed to ARVs?
Antiretroviral Pregnancy Registry
www.apregistry.com
What is the antiretroviral pregnancy registry?
- Surveillance study
- pregnancy outcomes in women exposed to antiretrovirals during pregnancy
- North America & Europe
Which ARVs used in PEP is there good pregnancy safety data?
Tenofovir Emtricitibine Darunavir Raltegravir Elvitegravir
What is rate of NEURAL TUBE DEFECT in pregnant women on DTG in Botswana vs women on other ARVs?
0.19% vs 0.11%
no statistical significance
Are ARVs used for PEP licensed for use in pregnant women?
No
Need to counsel woman
Is breastfeeding a contraindication to PEP?
NO
But need to consider individual risk of ART entering breast milk
When might PEP be considered in PrEP users?
Suboptimal adherence to PrEP
When is PEP indicated in PrEP users who have ANAL sex?
If less than FOUR (4) pills in past 7 days
When is PEP indicated in PrEP users who have VAGINAL, NEO-VAGINAL OR FRONTAL sex?
If less than SIX (6) pills in past 7 days
What is the HALF-LIFE of RALTEGRAVIR 1200mg daily?
8-12 hours
What is the HALF-LIFE of TDF/FTC 1200mg daily?
12-18 hours
but recent study suggest
31-37 hours
What are the missed dose rules for PEP?
If less than 48 hours since last dose:
- take dose as soon as remembered
or
- if time for next dose just take that
If a PEP dose is missed, how long before PEP should be discontinued?
If missed dose for more than 48 hours PEP should be discontinued
(DTG containing is >72 hours)
What seroconversion symptoms might present whilst on PEP?
Skin rash
Flu-like illness
If seroconversion symptoms present whilst on PEP what should the person do?
Attend for urgent medical review
If an HIV test is positive after PEP has started what should you do?
Continue PEP
Refer to HIV specialist
Why should ART not be stopped if HIV diagnosis made whilst on PEP?
Risk of significant VIRAL REBOUND and therefore INCREASED risk of onward TRANSMISSION
What advice should be given if high risk exposure takes place during the last few days of PEP?
ANAL sex and exposure last TWO (2) days of PEP, extend 2 days VAGINAL sex (or other), ensure PEP continued for 7 days
MSM prescribed PEP are associated with higher future HIV acquisition, what is the increase in those who access PEP once?
2.54
MSM prescribed PEP are associated with higher future HIV acquisition, what is the increase in those who access PEP MORE than once?
4.8
Repeat PEP users should be offered what?
Counselling around safer sex strategies
1 to 1 structured sessions
Condoms
PrEP