PreP Flashcards
What is the combination therapy used for PrEP?
Tenofovir (typically disoproxil + additional salt)
emtricitabine
Which trials are used/quoted in support of PrEP use?
iPrEx
PROUD
IPERGAY-OLE
How effective is PrEP for prevention of HIV infection?
iPrEx 44% reduction
PROUD 86% reduction
IPERGAY (extended) 97% reduction
Summarise iPrEx study?
phase 3
randomised, double blind, placebo-controlled
multi centre
DAILY dosing
MSM and trans male to female
South America, USA, Thailand, South Africa
HIV infections - TDF/FTC:placebo, 36:64
Summarise PROUD study?
phase 3 randomised open label multi centre DAILY dosing MSM and trans male to female sexual health clinics in England HIV infections - TDF/FTC:no PreP, 3:20
Summarise IPERGAY study?
phase 3 randomised, double blind, placebo-controlled multi centre ON DEMAND dosing MSM and trans male to female Canada and France HIV infections - TDF/FTC:placebo, 2:14
Of those with confirmed adherence to PrEP how many have acquired HIV?
3 case reports
What is the reason for HIV acquisition despite good adherence to PrEP?
2 of case reports had resistant virus
1 case report wild-type virus sensitive to tenofovir and emtricitabine
In which situation is PreP not recommended when HIV negative MSM have sex with HIV positive?
Partner has been on ART 6 months
and
viral load <200 (undetectable)
What is efficacy of PrEP dependent on?
Adherence
What side effects have been reported more commonly in those takin PrEP?
GI disturbance including nausea
Headache
What is the likelihood of a serious renal event on PreP?
Very low
Reversible (mostly)
What is the proportional effect on bone mineral density with PrEP?
Small net decrease 0.7-1%
No evidence of increased fracture risk
What effect does PrEP have on bacterial STI incidence?
Similar or Increase (dependent on study)
What is the rate of hepatitis C in MSM on PreP vs no PrEP?
4.8% vs 0.3-1.2%
What regimen of PreP can be used for heterosexual people?
DAILY
Summarise Partners PrEP study?
phase 3 randomised, double blind, placebo-controlled multi centre TDF vs TDF/FTC Daily dosing Heterosexual SERODIFFERENT couples Uganda and Kenya Efficacy - TDF 88% and TDF/FTC 91%
Summarise TDF-2 study?
phase 3
randomised, double blind, placebo-controlled
Daily dosing
Heterosexual men and women
Botswana
Concluded early ad underpowered
Efficacy - 62%; men > women (women 49%, men 80%)
Summarise FEM-PrEP study?
phase 3
randomised, double blind, placebo-controlled
multi centre
Daily dosing
Heterosexual WOMEN
Kenya, South Africa, Tanzania
No significant difference (likely due to low adherence)
Summarise VOICE study?
phase 2B
randomised, double blind, placebo-controlled
multi centre
TDF vs TDF/FTC vs vaginal tenofovir GEL
Heterosexual WOMEN
South Africa, Uganda, Zimbabwe
No significant difference (likely due to low adherence)
Which study is the most useful when considering PrEP in heterosexual men and women?
Partners PrEP study
What our virus does PrEP reduce the acquisition of?
HSV 2
When PrEP is used as a bridge to TasP for the seronegative partner how effective is it?
HIV incidence <0.05% per year vs >5% if not on PrEP
What are the differences between PrEP for heterosexual men and women and MSM?
MSM can have ON DEMAND or DAILY
Heterosexual DAILY only
Heterosexual can have tenofovir alone
What barriers to adherence to PrEP have been identified?
Perceived harm
Distinguishing between prevention and treatment
Social/community pressures/discouraged
What evidence is available for use of PrEP in pregnancy?
Partners PrEP - although stopped early pregnancy (average 35days)
2 USA clinics reported PrEP in pregnancy
Systematic review of TDF in HIV negative and chronic hepatitis B infection
Systematic review of TDF in HIV positive
Oral TDF-based PrEP appears SAFE in pregnancy, although no formal studies
Is PrEP detected in breast milk?
extremely low TDF
Higher levels of FTC (however 200-fold less than therapeutic dose)
aka VERY LOW concentrations TDF and FTC
Is there a change sexual behaviour that increases risk of STI in heterosexual people on PrEP?
Lack of data
What group of people at risk of HIV did the Bangkok Tenofovir Study review?
PWID
Summarise Bangkok Tenofovir Study?
phase 3
randomised, double blind, placebo-controlled
Daily dosing
TDF vs placebo
PWID (direct from drug treatment centres)
HIV infections - TDF:placebo, 17:33
What 3 drugs are typically used in chemise?
Crystal methamphetamine, ephedrine, GHB
What is BASHH/BHIVA recommendations on PrEP use in PWID?
Not recommended where needle exchange and opiate substitution programmes available
Consider on case by case
Chemsex relates to different demographic and should be explored
How much more likely are trans women to acquire HIV than the general population?
49 times higher
What factors contribute to trans women higher risk of HIV?
High level of discrimination Structural barriers to healthcare Violence Poverty High unemployment Housing instability
Which study did a subgroup analysis on efficacy of PrEP in trans women?
IPrEx
How many trans women acquired HIV in the PrEP vs placebo groups?
11 and 10; however no detectable PrEP at time of HIV seroconversion
PrEP should be taken DAILY by trans women and trans men, what is the only exception to this?
If they are exclusively having anal sex
Is there any drug-drug interaction of PrEP with feminising hormones?
Limited data but not expected due to different metabolism pathways
No difference in PrEP efficacy in women on hormonal contraception but these are lower doses
What has low adherence to PrEP in trans women been attributed to?
Fear of interaction with feminising hormones
Why is daily dosing PrEP required for those who have vaginal/frontal sex?
To achieve effective concentrations in vaginal tissue
Summarise Project PrEPare study?
Phase 2
Open-label PrEP demonstration and safety study
Young MSM (18-22yrs)
12 USA cities
Decrease in detectable tenofovir from 4-24 weeks
Majority in PrEPare 2 maintained good drug levels
4 HIV seroconversions (all no detectable drug levels)
What is the impact of PrEP on young men (18-22yrs) bone density?
More striking change than older subjects
>3% reduction in BMD
Reversible on stopping, however Z scores may not fully recover at 48 weeks
PrEP may pose particular risk to adolescents as critical period for attainment of peak bone mass
What should be considered in addition to PrEP for young men?
Endocrine-focussed interventions such as calcium or vitamin D supplementation
(No data to support)
Should we do routine BMD scanning in young MSM on PrEP?
No
What are the 3 sites that TDF and FTC levels are assessed in pharmacokinetic studies and for time-to-clinical protection assessment?
Lower gastrointestinal tract
Peripheral blood mononuclear cells (PBMCs)
Female genital tract (FGT)
What is tenofovir-diphosphate (TFV-DP)?
Active metabolite of TDF
How many days will it take to achieve a PBMC TFV-DP concentration that will result in 99% HIV risk reduction ? (‘protective concentrations’)
5 daily doses
How many days will PBMC TFV-DP concentrations achieve an HIV risk reduction of >90% when PrEP is stopped? (‘protective concentrations’)
7 days
Which drug in PrEP shows highest levels in genital secretions compared to rectal or blood levels?
Emtricitabine (FTC or FTC-TP)
How long is FTC-TP detectable in genital and rectal tissues?
2 days
Where are the highest levels of TFV-DP detected? How long do they remain detectable?
Rectal tissue (100-fold higher) 14 days
What is the time to steady state for TFV-DP in rectal tissue?
5days, however high penetration at 24 hours
Why is it possible to dose PrEP as little as 2 hours before sex?
FTC steady state reached at 2 hours in rectal tissue; this may explain the findings in IPERGAY that suggest the 2-24 hour period for first dose
How long should PrEP be taken before stopping after last sex?
Anal sex - 48 hours
Vaginal sex - 7 days
For anal sex, If PrEP is interrupted how should the person restart?
If less than 7 days since last dose PrEP can be re-started with single dose
How long should PrEP be taken for before it is effective in vaginal sex?
7 days; however should be counselled to start with double dose incase unable to wait 7 days although no evidence to support
How long should PrEP be taken for before it is effective at reducing risk of HIV with IVDU?
7 days as takes longer to achieve protective concentrations in blood
BASHH/BHIVA - who is recommended to be offered PrEP?
HIV negative MSM or TRANS WOMEN condoles anal sex past 6 months and ongoing
HIV negative individuals condoles sex with HIV positive partner <6months ART and viral load >200
What other population groups might make you consider offering PrEP?
Heterosexual black African men and women Recent migrants to UK Transgender women PWID Sex workers
What clinical scenarios might make you consider offering PrEP?
Rectal bacterial STI past year
Bacterial STI or hepatitis C past year
PEPSE past year, especially if repeat courses
What sexual behaviour might make you consider offering PrEP?
Condomless sex with partners unknown HIV status, especially if anal or multiple
Sex with partners from population group or country with high HIV prevalence
Chemsex/group sex
Condoles vaginal sex + other vulnerabilities
When could PrEP be considered for PWIDs?
Sharing injecting equipment
Injecting in unsafe setting
No access to needle or syringe programmes or opioid substitution
What factors may affect sexual autonomy and therefore increase risk of HIV?
Inability to negotiate/use condoms
Coercive/violent power dynamics in relationship
Precarious housing or homelessness
Risk of sexual exploitation/trafficking
Describe the incidence of HIV in the following: MSM overall, history of bacterial STI or rectal bacterial STI?
MSM overall 1.8/100
bacterial STI (past 12 months) 3.3/100
rectal STI 43.9/100
Clear correlation between STIs and sexual behaviour and ongoing HIV risk
What is the HIV incidence associated with chemsex?
11.6/100
Which studies support U=U?
HPTN052
PARTNER study
A detailed history should be taken for PrEP assessment. What information should be gathered about sexual behaviour?
Gender and sexuality of partners
Number of sexual partners in previous 6 months
Condomless sex in previous 6 months (anal or vaginal)
Sexual partners who are HIV positive and not on ART for >6 months with an HIV viral load <200 copies/mL
History of chemsex
During PrEP assessment What information should be gathered about STI history?
History of bacterial STI
History of rectal bacterial STI
HIV and STI testing history
History of PEP in the previous 12 months
During PrEP assessment What information should be gathered about medical and other relevant history?
Past medical history (with particular reference to RENAL and BONE problems)
Psychiatric/mental health history
Drug history (with particular reference to NEPHROTOXIC drugs)
History of injecting drug use including details of sharing needles or injecting equipment
What education prior to PrEP start should be given?
HIV transmission how PrEP works side effects of PrEP medication adherence and efficacy dosing schedule lead-in time to protection STI/HIV testing other HIV prevention strategies
What are the other HIV prevention strategies?
- condoms
- safer IVDU
- PEPSE
- psychosexual/health advisor support
- sexual health peer support
- drug and alcohol support
- mental health services
What are the typical symptoms of primary HIV infection?
Fever Rash Headache Malaise Arthralgia Sore throat
If there has been a high risk exposure in prior 4 weeks to starting PrEP, should PrEP be withheld until end of window period?
No, if ongoing risk of HIV and no symptoms suggestive of primary HIV infection
Repeat HIV test 4 weeks after PrEP initiation
What factors increase the risk of renal injury with PrEP use?
> 40 yrs old
Concomitant nephrotoxic medication
Hypertension
Diabetes
Which CrCl calculator is recommended in PrEP guidelines?
CKD-EPI
In chronic ACTIVE hepatitis B infection, what advice should be given in context of PrEP?
TDF/FTC can treat HBV
DAILY dosing only
Importance of ADHERENCE
risk of rebound viraemia and HEPATIC FLARES including fulminant liver damage
if stopping PrEP should be in discussion with specialist service and close follow up of LFTs and Hep B sAg
What additional risk factors increase risk of bone loss, to be considered when prescribing PrEP?
> 50 yrs (Female > Male)
Concomitant medications especially steroids
low BMI
Smoking
Excess alcohol
Hx of osteoporosis, osteomalacia or osteopenia
Which group can tenofovir disoproxil be used alone as PrEP?
Heterosexual men and women only
What should the time-to-protection advice be for men who have sex with women starting PrEP?
No clear evidence
Recommend 7 days
What is the estimated HIV risk reduction as adherence increases - twice, four times or seven times per week?
twice = 76% four = 90% seven = 99%
When might PEP be considered for someone prescribed PEP? Consider for MSM/trans and cis men and women.
If less than 3 tablets in past 7 days (ie taken 2 or less tabs in past 7 days)
If last PrEP dose >7days before
Threshold lower is vaginal sex consider if >48 hours since last PrEP or less than 6 tabs past 7 days
What baseline tests should be performed prior to initiating PrEP?
HIV serology + POCT if possible STI screen Hepatitis B and C screening Creatinine, eGFR and urinalysis uHCG if indicated
What to do if Atypical testing results on HIV serology whilst on PrEP?
Discontinue PrEP
retest 4 and 8 weeks
If a suspected seroconversion illness occurs whilst on PrEP what is the recommendation?
Intensify ART whilst awaiting further investigation
What are the indications to stop PrEP?
Reduction/no risk of HIV acquisition
HIV infection
Poor adherence despite attempts to support/improve
What precaution/assessment should be made before stopping PrEP?
assess for HBV infection is not immune
Continue TDF/FTC if HBV infection
If PrEP stopped close monitor of LFTs
