1. WHO technical brief on event-driven PrEP (ED-PrEP)

2. Rapid evolution of WHO PrEP recommendations and technical guidance
PrEP for SDC, MSM and TG in the context of demonstration projects (conditional recommendation)
PrEP for MSM (strong recommendation) Other KP (conditional)
PrEP for people at substantial HIV risk (≈3 per 100 person years) (strong recommendation)
PrEP drugs in EML (TDF/FTC; TDF/3TC; TDF);
WHO PrEP Implementation tool
2018 – Module on PrEP for adolescents
PrEP app
2019 – Module on M&E and technical brief on ED PrEP for MSM and STIs and eLearning tools

3. Countries with PrEP policies, July 2019
73 countries (+23 pending)
By July 2019, 73 countries have PrEP Policies - including clinical guidelines; 23 are pending
Not necessarily implemented
37 countries have pending policies
Source: Global AIDS Monitoring (GAM) 2019

4. Number of people who used PrEP at least once (2018)
Sources: USA: Sullivan et al., 2018; WHO Regional & Country Offices; Ministries of Health; Global AIDS Monitoring

5. Technical brief on event-driven PrEP (ED-PrEP) for MSM
The technical brief presents:
Current evidence on safety and efficacy of ED-PrEP
Rationale for offering ED-PrEP as an alternative to daily oral PrEP to men who have sex with men (MSM), as part of comprehensive HIV prevention and sexual health services 
Event-driven PrEP (ED-PrEP) dosing considerations for oral PrEP containing TDF for MSM
Messaging on how MSM can switch from ED-PrEP to daily dosing (and vice-versa). 
Event-driven (ED-PrEP), “2+1+1”, “on-demand”, “non-daily”, “event-based”, “pericoital” and “intermittent” PrEP.
This can be confusing for both health-care providers offering PrEP and for individuals seeking PrEP services. In this technical brief, we employ the term “ED-PrEP”. 

6. Current evidence on ED-PrEP
3 Randomized controlled trials (RCTs) evaluated ‘intermittent PrEP’: IAVI Uganda and IAVI Kenya (small sample size and methodological issues; not included in WHO meta- analysis); IPERGAY
IPERGAY (France, Canada) (n= 400): PrEP dosing (first dose 2-24h before sex; second dose 24h after the first one; third dose 48h after the first one)
86% reduction in HIV risk in the placebo controlled randomised phase (Median 15 pills taken/month; 86% in active drug arm had TDF concentration consistent with PrEP use in the previous week)
97% reduction in HIV risk in open label extension
Prevenir (2018) observational study in Paris (53% chose ED-PrEP)
0 infections in ~500 person years of ED PrEP; 20% used PrEP and condoms (2018)
No evidence among women, transgender persons, heterosexual men
ADAPT (in women; South Africa): more frequent PrEP use in daily PrEP vs.time- or event-driven arm (higher drug concentration).
JM Molina et al, New Engl J Med 2015; Lancet HIV 2017.

7. ED-PrEP: acceptability and preference
% of MSM choosing event driven
Belgium: 23.5% chose ED-PrEP (Reyniers T 2018)
Canada: L’Actuel: 22% when offered as alternative (Greenwald Z et al, 2017)
China: 58% interested in ED-PrEP trial (Mao X et al, 2017)
France: 40% interested in ED-PrEP trial (Lorent N et al, 2012);
53% in Prevenir study (Molina J-M et al, 2018);
76% (Noret M et al, 2018)
The Netherlands: 27% chose ED-PrEP (Hoornemborg E et al, 2019)
UK: ~17% (Public Health England, PrEPster, IWantPrEPNow)
USA: 74% in MSM who declined daily dosing (Beymer MR at al, 2018) UK

8. When to consider ED-PrEP?
For whom is ED-PrEP appropriate? 
For whom is ED-PrEP NOT appropriate? 
MSM*:
who would find ED-PrEP more effective and convenient 
who has infrequent sex (for example, sex less than 2 times per week on average) 
who is able to plan for sex at least 2 hours in advance, or who can delay sex for at least 2 hours 
cisgender women or transgender women 
transgender men having vaginal/frontal sex 
men having vaginal or anal sex with women 
people with chronic hepatitis B infection.
At this time there is evidence on safety and efficacy/effectiveness for ED-PrEP only for men who have sex with men (men exposed through receptive or insertive anal sex with other men) 
* There is evidence on the efficacy and safety of ED-PrEP only for men who have sex with men (receptive and/or insertive anal sex).

9. What’s the 2+1+1? Dosing regimen for MSM
If sex continues beyond one day, a user of ED-PrEP can stay protected by taking another pill each day as long as sex continues and stopping 2 days after the last sex act. Conversely, if an individual starts daily oral PrEP, but then sex becomes infrequent and predictable, ED-PrEP can be used instead. 
Given the clinical evidence for the efficacy of ED-PrEP among men who have sex with men and this recent pharmacological modelling, it is suggested that men who have sex with men starting PrEP begin with a single loading dose of two tablets of FTC/TDF (or 3TC/TDF) taken two to 24 hours before sex, whether the intention is to use daily PrEP or ED-PrEP. PrEP programmes for men who have sex with men that offer both the event-driven and daily approaches usually advise that PrEP can be stopped after two daily doses following the last sexual exposure.
“Loading dose”
Is appropriate if sex can be predicted or delayed by at least 2 hours, or occurs infrequently (e.g. < 2 times per week).

10. Daily PrEP or ED-PrEP for MSM?
For all people at risk for HIV, daily oral PrEP should be used once daily during periods of frequent sex or when sex is unpredictable. PrEP can be stopped when no sex occurs. 
Seasons of risk and frequency of risk exposure may vary from person to person and for the same person overtime.
For men who have sex with men oral daily PrEP and ED-PrEP can be offered as options, and the choice can be based on a person’s circumstances and preferences, as determined by what best fits their lifestyle, including the frequency and predictability of sex and whether sex is anticipated. 
Daily dosing is appropriate for clients where the occurrence of sex cannot be predicted and for those whose potential exposures to HIV are more frequent than 2 times per week, such that ED-PrEP would be taken so frequently that it would effectively resemble daily PrEP. 

11. Advantages and benefits of ED-PrEP
Disadvantages
Offer flexibility, choice, and convenience for MSM who may be at high HIV risk for brief periods or have sex infrequently
Adaptable to “seasons of risk”
Less pill burden
Less toxicity
Reduced costs
Improved continuation among MSM who find daily pill-taking challenging. 
Needs some planning before sex
Remembering to take post-sex dose
Potentially stigmatizing (may identify as MSM)
Adolescents may need more support to adopt and adhere to 2+1+1

12. Conclusions
ED-PrEP is safe and highly effective in reducing HIV infection in MSM and alternative to daily PrEP for MSM. ED not for all, and daily PrEP may be more feasible for many MSM and in some settings.
Countries may consider including both daily dosing and ED-PrEP for MSM in national guidelines and protocols. 
Education and support for both ED-PrEP and daily dosing are necessary to aid choice; and HIV testing is recommended every 3 months regardless of dosing schedule.
Caution should be taken when documenting ED-PrEP use in settings where same-sex activity is criminalized (confidentiality and data protection).
Need more data on ED-PrEP in other populations

13. Available at: www.who.int/hiv/pub/prep/211/ Acknowledgements WHO
Rachel Baggaley
Ioannis Hodges-Mameletzis
Shona Dalal
Michelle Rodolph
Contributors
Robert Grant
Jean-Michel Molina
Reviewers
Photographs ©PrEPster/Ajamu Studio
The brief is embargoed until 14:30 on Tuesday 23 July. The link will be live after that.
Available at: