PEPSE / PrEP Flashcards
factors influencing efficacy of PEPSE
timing of initiation transmission of a resistant virus variable genital tract penetration of the drug poor / non-compliance further high risk sexual exposures
Factors increasing the risk of HIV transmission
High viral load of the source
breaches in the mucosal barrier - ulcers / trauma
menstruation / other bleeding (theoretical)
other STI in a HIV +ve pt not on ARVs
Ejaculation
Non-cicumcision
discordant VL in the genital tract
HIV prevalence sex workers
- in UK / Western Europe
- Central Europe
- Eastern Europe
- Male CSWs
HIV prevalence sex workers
- in UK / Western Europe = <1%
- Central Europe = 1-2%
- Eastern Europe = 2.5 - 8%
- Male CSWs = 14%
Which medications are usually used for PEPSE
Tenofovir- DF and emtricitabine (Truvada)
AND
raltegravir 400mg BD
Timeframe from sexual exposure to start PEPSE
72 hours
ideally within 24 hours
At what transmission risk is PEPSE indicated
> 1 : 1000 - recommend
1 : 1000 - 1 : 10,000 - consider
<1 : 10,000 - not required
Is PEPSE required if the source is HIV +ve on ART with an undetectable VL
No
If on ART with a sustained undetectable VL for a minimum of 6 months
HIV risk of transmission per exposure for:
receptive anal intercourse - average
- with ejaculation
- without ejaculation
HIV risk of transmission per exposure for:
receptive anal intercourse - average = 1 : 90
- with ejaculation = 1 :65
- without ejaculation = 1 : 170
HIV risk of transmission per exposure for:
insertive anal intercourse - average
- not circumcised
- circumcised
HIV risk of transmission per exposure for:
insertive anal intercourse - average = 1:666
- not circumcised = 1: 161
- circumcised = 1:909
HIV risk of transmission per exposure for:
- insertive vaginal intercourse
- receptive vaginal intercourse
HIV risk of transmission per exposure for:
- insertive vaginal intercourse = 1 : 1219
- receptive vaginal intercourse = 1 : 1000
If the source is known HIV +ve not on ART what is the risk of transmission for: - human bite - semen splash to eye - oral sex - receptive or insertive - blood transfusion - needlestick injury - sharing injecting equipment
If the source is known HIV +ve not on ART what is the risk of transmission for: - human bite = <1 : 10, 000 - semen splash to eye = <1 : 10, 000 - oral sex - receptive or insertive = <1 : 10, 000 - blood transfusion = 1 : 1 = 100% - needlestick injury - 1 : 333 - sharing injecting equipment 1 : 149
If the HIV transmission risk falls in the consider PEPSE range then what factors may suggest it should be given
Source patient has a diagnosed STI
breaches in the mucosal barrier (ulcers, trauma)
primary HIV infection in the source patient
victim of sexual assault / traumatic intercourse
> 1 high risk sexual contact within 72 hours
menstruation or other bleeding
Calculation for estimating the risk of HIV transmission
Risk of HIV transmission = risk source is HIV +ve X risk per exposure
e. g. Manchester MSM = x receptive anal intercourse with ejaculation
8. 6. / 100 X 1/65 = 1 / 757
Management of a patient requiring PEPSE in A+E
sexual history
medical history,
medication and OTC, Allergies
alcohol , smoking
4th generation POCT Send 4th generation venous sample for HIV, STS, HBV and HCV U+Es, LFTs Urine ACR UPT if required 1st dose of HBV vaccination
Management of a patient requiring PEPSE in a GUM clinic
sexual history
medical history,
medication and OTC, Allergies
alcohol , smoking
4th generation POCT Send 4th generation venous sample for HIV, STS, HBV and HCV STI screen U+Es, LFTs Urine dip for proteinuria - if present send urine ACR UPT if required Consider emergency contraception 1st dose of HBV vaccination
What should we advise a patient when starting PEPSE
rationale for PEPSE
drugs are not licensed for PEPSE but commonly used
full course = 28 days
continue PEPSE if baseline bloods comeback +ve
Usually no or mild SE - GI upset
Baseline liver and renal function - drugs occasionally affect these
Safe sex / risk reduction advice / avoid further high risk sexual exposures
PEPSE not 100% effective
FU HIV test 12/52
What follow should be offered for patients started on PEPSE
review bloods at 48 hours
2 / 52 repeat STI screening, check adherence, SE, 2nd HBV vaccination
12 / 52 repeat HIV and STS bloods
Management of a patient who attends GUM clinic after receiving a 5/7 starter pack of PEPSE from A+E
baseline bloods if not done or not available - HIV, STS, HBV, HCV, U+E, LFTs urine ACR Ask re timing of PEPSE and adherence Any SE Continue PEPSE for full 28 days STI screening 1st HBV vaccination if not done offer HAV vaccination + / - HPV FU in 2/52 and 3/12 health promotion / safer sex / risk reduction
Management of an <16yo requiring PEPSE
Assess per adult guidelines if >13 yo and >35kg
Commence adult dose
refer to HIV transition team for follow up with paeds HIV team
if <13yo or <35kg - refer to CHIVA guidelines and refer to the paeds HIV team
medication type and dose is age and weight dependant
Management of a pregnant patient requiring PEPSE
Pregnancy does not alter the decision to start PEPSE
calculate risk and offer if >1:1,000
POCT,
4th gen venous sample,
sexual heath screening - incl STS, HBV, HCV
Serum U+E
LFTs
urine dip for protein
explain PEPSE medications are unlicensed in pregnancy
recommendations for missed doses of PEPSE
Always reinforce the importance of adherence
<24 hours since last dose - take missed dose immediately and next at usual time
24 - 48 hours since last dose - continue PEPSE
> 48 hours since last dose - stop PEPSE
Management of a further high risk sexual exposure during the last 2 days of a PEPSE course
continue PEPSE for 48 hours after last high risk exposure
Discuss PrEP
when should patients on PEPSE be advised to return for an urgent review?
rash
flu-like illness
(to exclude HIV sera-conversion)
Management of a patient on PEPSE who has a positive baseline HIV test
continue PEPSE until reviewed by a HIV specialist
Alternative to raltegravir in PEPSE for patients who cannot take it
dolutegravir
integrase inhibitor
Why is abacavir not reccomended for PEPSE
8% of patients will have a hypersensitivity reaction
Requires HLA-B * 570 screening test before initiation
Abacavir = NRTI
Rationale behind PEPSE
window of opportunity to avert HIV infection
inhibiting viral replication following exposure
HIV crosses a mucosal barrier
takes 48–72 h before HIV detected in regional lymph nodes
take 5 days before HIV detected in blood
Animal models = Initiation of ART reduces dissemination + replication of virus in all tissues if initiated early after inoculation
What should be considered regarding PEPSE if a person has had multiple exposures within 72 hours
cumulative risk should be considered
HIV prevention strategies
Condom use - M or F Safer sex PEPSE PrEP ARVs - U=U and prevention of vertical transmission HIV testing STI testing and treatment Blood screening Not sharing needles (Male circumcision)
Advice regarding PEPSE if source HIV status is unknown
Attempt to contact partner and arrange testing of them - then stop PEPSE if they test negative
Is PEPSE recommended if the source HIV status is unknown but they are from a risk-group or country of high HIV prevalence (> 1%)
Routinely recommend for: - Receptive anal sex Consider for : - Insertive anal sex - Receptive vaginal sex - Insertive vaginal sex - Sharing of injecting equipment
In what circumstance would PEPSE be recommend when the source is known HIV positive with an undetectable VL
( < 200)
Source does not have a confirmed VL < 200 for >6 months
Regarding a patient started on PEPSE - what information should be obtained from a HIV positive source?
plasma HIV viral load
resistance profile
treatment history of the source
What is the risk of HIV transmission from a semen splash to the eye
no documented HIV transmissions via this route
Is PEPSE recommended ollowing fellatio with ejaculation
PEPSE is ‘not-recommended’
The risk is <1/10,000
Case reports of oral transmission exist
Offer PEPSE in extreme circumstances
e.g. primary HIV infection and oropharyngeal trauma/ulceration
Is PEP recommended for a needlestick injury from a needle found in the community
e.g. on the street
No
- not possible to determine if the needle has been used and for what purpose
- HIV status of the source unknown
- interval between needle use and the exposure
what is the timeframe for HIV becoming non-viable
e.g. on an abandoned needle in the community
HIV becomes non-viable within a couple of hours -
once the blood has dried
viable HIV cannot be detected after 24 h
Items to discuss with individual initiating PEPSE:
- rationale for PEPSE
- lack of conclusive data for efficacy of PEPSE
- potential risks and side effects
- arrangement for early follow-up with an HIV/GU medicine clinician
- Pre-test discussion and HIV test (4th generation laboratory test).
- continue PEPSE for 28 days if the baseline result is negative.
- The need to have a follow-up HIV test 8–12 weeks post-exposure.
- safer sex for the following two months
- Emergency contraception
- Coping strategies, assessment of vulnerabilities, social support.
- offer ongoing risk reduction work / referral to
psychology
Is PEP recommended after human bites
No
The risk of transmission is unknown
Likely to be extremely small
Can consider in extreme circumstances - blood in the oropharynx from trauma or deep wounds were caused by the bite
Is PEPSE recommended after sexual assault
transmission of HIV is likely to be increased as a result of any trauma following aggravated sexual intercourse (anal or vaginal)
recommend PEPSE
particularly if the assailant from high prevalence group
Duration of PEPSE
28 days
Why is Nevirapine based PEP not recommended
almost 10% experience grade 3 or 4 hepatotoxicity and serious liver toxicity (requiring transplant)
What medicagtions of OTC preparations should be avoided with PEPSE
raltegravir (and dolutegravir) = low risk of druginter actions,
Avoid concomitant use of metal cation containing antacids and multivitamins s
Dose-adjustment required with concomitant rifampicin use
Baseline investigations when initiating PEPSE
HIV test - 4th generation Hep B sAg (if not vaccinated) Hep B immunity Hep C Syphilis STI testing Creatinine ALT Urinalysis or uPCR Pregnancy test
What investigations should be offered at 14 days after initiating PEPSE
STI testing
Creatinine - if abnormal at baseline
ALT - Only if abnormalities at baseline / Hep B or C co- infected, or on Kaletra
Urinalysis or uPCR - Only if abnormalities at baseline
Pregnancy test - if required
What investigations should be offered at 8–12 weeks after initiating PEPSE
Repeat HIV test Repeat Syphilis test Repeat Hep B / Hep C STI testing - if further risk pregnancy test - if required
What is the advice for patients starting on PEPSE if they develop a rash or flu-like symptoms
skin rash or flu-like illness during or after taking PEPSE should attend for URGENT review
to exclude HIV seroconversion
Management of individuals who repeatedly present for PEPSE or with ongoing high-risk behavior
Meet with a health Sexual Health Adviser
+/- psychologist
counselling around safer sex strategies
Which patients should PrEP be recommended for?
HIV-negative MSM identified at increased risk of HIV acquisition through condomless anal sex in the previous 6 months + ongoing condomless anal sex
what medication is used as PrEP
Truvada = Tenofovir-DF and Emtricitabine
What is the daily PrEP regimen
Daily PrEP = 1 pill per day
Lead-in time for daily PrEP = 7 days
Best taken at the same time each day
With or without food
Benefit of daily PrEP regimen
can miss an occasional pill and still have adequate protection
What is the On Demand PrEP or Event Based Dosing PrEP regimen
Only suitable for anal sex
Really important not to miss any doses
take 2 pills 2 – 24 hours before sex
take 1 pill 24 hours later
take 1 more pill 24 hours after that
If having more sex continue to take a pill every 24 hours until you have 2 sex-free days
For which patients is on demand / event based dosing of PrEP not recommended
Active hepatitis B infection
- drugs in PrEP suppress HBV - so starting and stopping PrEP can cause viral flare-ups and liver inflammation
PrEP impact on renal function
Modest, but statistically significant decline in renal function with daily tenofovir - emtricitabine
Mostly reversible
Serious renal events rare
PrEP impact on bone mineral density
a small decrease in BMD of 0.7–1% from tenofovir + emtricitabine
no long-term data
not associated with fractures
Why is on demand PrEP not recommended for heterosexual vaginal intercourse
No studies have evaluated the efficacy of an on-demand oral PrEP regimen in heterosexual men and women
Would PrEP interact with oral contraception
No
Tenofovir and emtricitabine do not affect liver enzymes
Can PrEP be used in pregnancy or breastfeeding
Yes
existing data supports the safety of Tenofovir and emtricitabine in pregnancy or breastfeeding
if they are at increased risk of HIV acquisition
What is meant by PrEP bridging to TasP
Use of PrEP in the HIV negative partner
until the HIV positive partner is established on ARVs for treatment as prevention = on treatment with VL <50 for 6m+
Does PrEP prevent HIV transmission in people who inject drugs?
Unclear
No UK data
limited evidence from Thai study - suggests reduction in
HIV incidence
What has been suggested as the reason that PrEP for trans-women has been less effective in studies than for cis-men or cis-women
poorer adherence (as measured by drug concentrations)
Regarding PrEP use in young men (<25) what health impacts should be considered
Reduces BMD
Appears to be reversible
may be a particular risk for adolescents as this is a critical period for attainment of peak bone mass
What is the advice if daily dosing of PrEP has been interrupted and anal sex is expected to occur
If it is less than 7 days since the last dose then PrEP can be re-started with a single dose
and continue for at least 48 hours after last sexual act
What is the advised regimen for taking for PrEP for patients at risk from vaginal sex
Daily dosing
Start PrEP 7/7 before vaginal sex and continue for 7/7 after the last sexual risk
What is the advised regimen for taking for PrEP for MSM who are also at risk from injecting drug use
Daily dosing advised
Take for 7/7 before and continue for at least 7/7 after the risk
for patients who are at risk of HIV from injecting drug use - Why does PrEP need to be started 7/7 before and continued for 7/7 after
PrEP takes longer to achieve protective concentrations in the blood than in the GI / Anal mucosa
for patients who are at risk of HIV from vaginal intercourse - Why does PrEP need to be started 7/7 before and continued for 7/7 after risk
PrEP takes longer to achieve protective concentrations in the vaginal mucosa than in the GI / Anal mucosa
In which cases does BASHH / BHIVA recommend PrEP
1) - HIV-negative MSM / trans women who report condomless anal sex in the previous 6 months + on-going condomless anal sex.
2) - HIV-negative individuals having condomless sex with HIV positive partners, unless the partner has been on ART at least 6 months and viral load is <200 copies/mL
In what circumstance does BASHH / BHIVA recommend that PrEP may be considered on a case-by-case basis
HIV-negative individuals considered at increased risk due to a combination of factors
• black African men / women
• Recent migrants to the UK
• Transgender women
• People who inject drugs
• Sex workers / transactional sex
• Bacterial STI or HCV in last year
• Required PEPSE in last year
• High-risk sexual behaviour - multiple condomless sex acts with partners of unknown HIV status
• Chemsex
• Group sex
• Sharing injecting equipment / injecting in an unsafe setting
• Coercive / violent power dynamics in relationships
• Precarious housing / homelessness
• Risk of sexual exploitation / trafficking
Education prior to starting PrEP
information on HIV transmission how PrEP works potential side effects of PrEP medication adherence and efficacy dosing schedule lead-in time to protection STI/HIV testing other HIV prevention strategies
What is the strongest factor linked to PrEP efficacy
adherence
Possible side effects from PrEP
Usually well tolerated possible transient side effects • diarrhoea • headache • vomiting • loss of appetite encourage to manage with simple analgesics and anti-emetics
Signs of acute HIV infection - to warn patients about when using PrEP
= seroconversion - Advise to return to clinic if concerned • fever • lethargy • Swollen lymph nodes • Swollen tonsils • sore throat • myalgia / arthralgia • diarrhoea • rash
Explanation of HIV transmission for patients before starting PrEP
HIV = virus
only transmitted through specific activities.
Only certain body fluids can transmit HIV from a HIV infected person - blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk
These fluids must contact a mucous membrane / damaged tissue or be directly injected into the blood
HIV mainly spread by
- anal / vaginal sex
- Sharing needles / drug equipment
- mother to child during birth or breastfeeding
- Needlestick injury
- Blood transfusion / blood products / organ transplant from HIV infected sources
Baseline investigations before a patient starts PrEP
POCT HIV test HIV serology - 4th generation Hep B Hep C - if risk Syphilis STI testing Creatinine + eGFR ALT Urinalysis or uPCR Pregnancy test
Advice if a patient becomes pregnant while on PrEP
if a patient is pregnant when starting PrEP or becomes pregnant while on PrEP
Advise continuing PrEP during pregnancy or breastfeeding if there is an ongoing risk of HIV acquisition
In what circumstance does on demand dosing for PrEP not require a loading dose of 2 pills
A loading dose of two pills is required 2 - 24 hours before sex
unless the last PrEP dose was less than one week earlier in which case they can be instructed to only take one pill 2 - 24 hours before sex
What is the advice re how to take on demand PrEP if there are multiple consecutive episodes of sex
loading dose = 2 pills 2 – 24 hours before sex
take 1 pill 24 hours later
take 1 more pill 24 hours after that
Continue taking every 24 hours until 48 hours after the last sexual intercourse
What regimen of PrEP is recommended for `trans-women and trans-men
and why
Daily dosing
Absence of data for on-demand dosing in trans patients
What is Intermittent dosing of PrEP?
Taking 4 tablets per week on intermittent days
What monitoring is recommended whilst a patient is on PrEP
HIV testing - 3 monthly
STI screening - 3-monthly
HCV testing - 3-monthly - in MSM, trans women + others at on-going risk of HCV
Renal function:
- If eGFR >90 at baseline + follow up and patient <40yo - advise annual eGFR
- If eGFR 60–90 / aged >40 years or risk factors for renal impairment - monitor renal function at least 6 monthly
- If eGFR <60 - discuss the risks and benefits of continuing PrEP
Discuss contraception + assess pregnancy risk @ follow up visits
Indications for stopping PrEP
- Positive HIV test - Refer to specialist HIV service
- Chronic HBV infection - DW Hepatitis specialist re safety of PrEP
- a reduction in risk of HIV acquisition as defined by eligibility criteria
- poor adherence + attempts at adherence support have failed
- Review if eGFR falls <60 - renal input
what drug interactions should be considered when offering PEPSE including raltegravir or dolutegravir
raltegravir and dolutegravir = low risk in-terms of drug–drug interactions
AVOID concomitant use of metal cation containing antacids and multivitamins if possible
Apart from side effects, what is another reason why (PIs) such as Kaletra (lopinavir / ritonavir) or darunavir / ritonavir are not preferred options for PEPSE
More drug-drug interactions
e.g. interacts with contraception to reduce efficacy
