1. PROUD: Results and participant experiences Presented by Mitzy Gafos, behalf of the PROUD team http://www.proud.mrc.ac.uk/

2. Clinical trial evidence for oral PrEP Effect size (CI) iPrEx: daily Truvada (MSM - America’s, Thailand, South Africa) 44% (15; 63) TDF2: daily Truvada (Heterosexuals men and women- Botswana) 62% (22; 84) Partners PrEP: daily Truvada (Discordant couples – Kenya, Uganda) 75% (55; 87) Partners PrEP: daily Tenofovir (Discordant couples – Kenya, Uganda) 67% (44; 81) FEMPrEP: daily Truvada (Women – Kenya, South Africa, Tanzania) 6% (-52; 41) MTN003/VOICE: daily Truvada (Women – South Africa, Uganda, Zimbabwe) -4% (-49; 27) Bangkok Tenofovir Study: daily Tenofovir (IDUs– Thailand) 49% (10; 72) MTN003/VOICE: daily Tenofovir (Women - South Africa, Uganda, Zimbabwe) -49% (-129; 3) Effectiveness (%) Source: Adapted from Abdool Karim SS. Lancet 2013

3. PROUD Pilot GMSM reporting condomless anal sex last/next 90days; 18+; and willing to take a pill every day Risk reduction includes Truvada AFTER 12M Randomize HIV negative MSM (exclude if treatment for HBV/Truvada contra-indicated) Main endpoints in Pilot: recruitment and retention From April 2014: HIV infection in first 12 months Follow 3 monthly for up to 24 months Risk reduction includes Truvada NOW

4. HIV Incidence Group No. of infections Follow-up (PY) Incidence (per 100 PY) 90% CI Overall23465.64.93.4–6.8 Immediate3243.51.20.4–2.9 Deferred20222.19.06.1–12.8 Effectiveness =86% (90% CI: 64 – 96%) P value =0.0001 Rate Difference =7.8 (90% CI: 4.3 – 11.3) Number Needed to Treat =13 (90% CI: 9 – 23) *174 courses of PEP for 85(31%) deferred

5. P=0.47 P=0.04 Sexual Behaviour

6. STIs Caveat Number of screens differed between the groups: e.g. Rectal gonorrhoea/chlamydia 974 in the IMM group and 749 in the DEF Adjusted OR=1.00, p=0.99

7. PROUD: In-depth Interviews Immediate 11 Deferred 14 Increased risk behaviour HIGH ADHERENCE 6 Same risk behaviour HIGH ADHERENCE 3 Increased risk behaviour 7 Increased risk behaviour LOW ADHERENCE 1 Same risk behaviour LOW ADHERENCE 0 Same risk behaviour 5 SPECIAL 1 SPECIAL 2 Purposeful Sampling: Risk-adherence matrix

8. Condom realities Condom use Pleasure Erection Intimacy Sobriety Risk taking NeverSometimes Want not to with partner Attempt to “I am not going to not bareback" “I felt like I was holding the lid on a boiling pot of water so hard that I just couldn’t hold it any more” “It was a form of self harm I would say” “If I thought someone was generally reckless then I would be somewhat wary about doing anything" “I’ve never reached organism inside of one which is an unbelievably frustrating thing” “It is an absolutely terrifying thing to him to think that he might infect me, it is his absolute worst nightmare” “I have my set of rules …I try to only have sex with people who are undetectable …I sometimes trust people that are top exclusively that are negative

9. PrEP positioning Exclusive Additional Alternative Partner type Partner status Positioning Ejaculation Condom use “I am more looking at the person now, everyone likes the meet up with a better looking person” “I would not go to the position of accepting ejaculate” “I have definitely experienced more as a bottom since, still very small as a percentage….I am more relaxed about allowing a guy to fuck me” “I have a partner who is HIV positive and we have gone without condoms since being on the study which we wouldn’t do before” “It slightly loosens the boundaries rather than taking them off altogether”

10. Impact of PrEP “I wanted to make him a bit less anxious about having sex with me, I just wanted to reassure him that I was taking additional precaution” “If I wasn’t taking it, sooner or later the inevitable is going to happen” “I will get a lot of extra piece of mind being on it” “It is like a defence mechanism, you know, don’t tempt fate” “It takes away any possible worry afterwards, I just feel like there is this protective bubble there” “It has been an absolute life saver… if I hadn’t been on it … I don’t know how I would have remained negative to be honest ” Reduced anxiety, fear, guilt, more in control, achieve desired sex “It certainly lets you feel better about yourself after sex” “I like it, it is a security blanket”

11. Perception of PrEP duration Seasons of risk – Until not sexually active, monogamous, married, children, bored of wild sex scene, deals with demons – Only 1 person expected to take long term “You don’t see many 55 year old men doing group sex, clearly it is a period, a moment … it is not going to be a lifetime” “I want to explore this wild sex scene that cities like London or Berlin can offer… but I am beginning to loose interest ”

12. Summary HIV incidence – was much higher than expected in PROUD, despite high PEP use Effectiveness – was greater in the real world than preceding placebo controlled trials, with an average adherence of 88% Other STIs – were no greater in those on PrEP or not on PrEP in PROUD, although very common in the study populations Sexual behaviour – changes in behaviour were limited in the quantitative data and this is supported by the qualitative data which shows slight amendments to existing high risk behaviours Periods – PrEP is perceived as an important additional prevention option for periods of risk Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection.

13. Acknowledgements (1) Study participants MRC CTU at UCL Sarah Banbury, Liz Brodnicki, Christina Chung, Yolanda Collaco-Moraes, Monica Desai, David Dolling, David Dunn, Mitzy Gafos, Sajad Khan, Brendan Mauger, Sheena McCormack, Yinka Sowunmi, Gemma Wood HIV & STI Dept, PHE Monica Desai, Sarika Desai, Noel Gill, Anthony Nardone, GUMCAD team, HIV team Clinics Vanessa Apea, John Saunders, Mags Portman (Barts Health NHS Trust), Christine Bowman (Sheffield Teaching Hospitals NHS Foundation Trust), Michael Brady (Kings College Hospital NHS Foundation Trust), Martin Fisher, Amanda Clarke (Claude Nichol Centre), Julie Fox (Guy’s and St Thomas’s NHS Foundation Trust), Richard Gilson (The Mortimer Market Centre), Charles Lacey (York Hospitals NHS Foundation Trust), Nicola Mackie (St Mary’s Hospital), Alan McOwan, Simone Antonucci (56 Dean Street), Iain Reeves (Homerton University Hospital NHS Foundation Trust), Gabriel Schembri (Manchester Centre for Sexual Health), Ann Sullivan (John Hunter Clinic for Sexual Health), Steve Taylor, David White (Heart of England NHS Foundation Trust)

14. Acknowledgements (2) Trial Steering Committee Independent members: Mike Adler (Co-Chair), Gus Cairns (Co-Chair), Dan Clutterbuck, Rob Cookson, Claire Foreman, Stephen Nicholson, Tariq Sadiq, Matthew Williams Investigator members: Brian Gazzard, Noel Gill, Anne Johnson, Sheena McCormack, Andrew Phillips Gilead: Matt Bosse, Rich Clarke, Jim Rooney, Murad Ruf University of Liverpool: Saye Khoo Independent Data Monitoring Committee: Anton Pozniak, Simon Collins, Fiona Lampe Community Engagement Group Community: Yusef Azad (NAT), Gus Cairns (NAM), Rob Cookson (LGF), Tom Doyle (Mesmac), Justin Harbottle (THT), Marion Wadibia (NAZ), Matthew Hodson (GMFA), Cary James (THT), Roger Pebody (NAM) Clinics:Anthony Bains, Alan McOwan (Lead), MRC CTU at UCL: Sheena McCormack, Mitzy Gafos, Annabelle South Social Science Advisory Group Interviewers: Caroline Rae, Gill Bell, Michael Rayment, Sonali Wayal, Will Nutland, Mitzy Gafos Advisors:Ingrid Young, Ford Hickson, Lisa McDaid, Marsha Rosengarten, Nicolas Lorente, Agata Pacho, Elizabeth Poliquin, Anthony Nardone, Catherine Dodds, Adam Bourne, David Dolling, Sheena McCormack, Rob Horne

15. FridaySaturdaySundayMondayTuesdayWednesdayThursdayFridaySaturdaySunday Ipergay : Event-Driven PrEP 2 tablets (TDF/FTC or placebo) 2-24 hours before sex 1 tablet (TDF/FTC or placebo) 24 hours later 1 tablet (TDF/FTC or placebo) 48 hours after first intake

16. mITT results Group No. of infections Incidence (per 100 PY) TDF/FTC20.94 Placebo146.6 Effectiveness =86% (95% CI: 40 – 99%) P value =0.002 Number Needed to Treat =18 Median number of pills/month (IQR): 16 pills (10-23) in the placebo arm 16 pills (12-24) in the TDF/FTC arm (p=0.84)

17. Adherence by Pill Count  Median number of pills/month (IQR): 16 pills (10-23) in the placebo arm and 16 pills (12-24) in the TDF/FTC arm (p=0.84)  48 participants (12%) received PEP 25 (13%) in the TDF/FTC arm and 23 (11%) in the placebo arm (p=0.73) 0 : full bottles returned (all tablets) Nb pills used / month missing : 294/2798 visits (10.5%) Percentage of participants 0 10 20 30 40 50 60 70 80 90 100 M1M2M4M6M8M10M12M14M16M18M20M22M24M26M28M30 Visits ] 0 - 4 ] ] 4-11] ]11-18] ]18-25] ]25-30] 3823523152882361901621431281151059388726345 N part..