Long term follow up of PROUD

1. Long term follow up of PROUD Evidence for high continued HIV exposure and durable effectiveness of PrEP E.White, D.Dunn, R.Gilson, A.Sullivan, A.Clarke, I.Reeves, G.Schembri, N.Mackie, C.Dewsnapp, C.Lacey, V.Apea, M.Brady, J.Fox, S.Taylor, J.Rooney, M.Gafos, N.Gill, S.McCormack, and the PROUD study group IAS, 23-26 July 2017, Paris, France

2. PROUD(Nov12-Nov16) HIV negative, G/MSM/TGW reporting condomless anal sex last/next 90days; 18+; clinic attendee; willing to take a pill every day Enrolled 544 Risk reduction includes Truvada AFTER 12M Randomised 269 Risk reduction includes Truvada NOW Randomised 275 Follow 3 monthly Endpoint: HIV infection in first 12 months Impact on sexual behaviour and other STIs

3. Background • PROUD reported early due to • unexpectedly high HIV incidence in the no-PrEP group (DEF) • very high effectiveness in the PrEP group (IMM) • Significantly more non-condom anal sex partners when the participant was receptive (bottom) • 21% IMM with 10 or more compared to 12% DEF • No major differences in STIs between arms, except • trend towards lower rectal chlamydia in DEF compared to IMM

4. For this analysis • Definitions • HIV infection if Ag/Ab negative at enrolment, then a reactive test confirmed by detection of virus • STI infection (yes or no, if yes the number) for syphilis, gonorrhoea or chlamydia by location since last visit • Stopped PrEP if last prescription was before 31May2016 • Deferred follow-up time from enrolment to • HIV test reactive and infection subsequently confirmed • 12 month visit when offered PrEP • Earlier visit after amended protocol when offered PrEP • Post-deferred follow-up time through to • Last HIV test in the study

5. PrEP starts over calendar time Deferred phase Post-deferred phase

6. PrEP prescriptions *Up to last prescription

7. Participants continuing to collect PrEP prescriptions*, by time since initiation *Defined as any prescription since 31/05/2016

8. HIV incidence in the deferred and post-deferred phases

9. HIV tests and PrEP prescriptions for the 10 who acquired HIV after starting

10. STI incidence in the deferred and post-deferred phases Lacey et al BASHH June 2017

11. Clinic burden

12. Strengths and weaknesses • The end was difficult to plan without access to PrEP in the NHS • Study schedule for STIs followed standard of care and this changed from 6m to 3m in 2014 • Participants on PrEP more likely to attend • Matching against national HIV infection dataset held by PHE identified 1 new infection • Able to use routine STI clinic data, at least in enrolling clinic

13. Conclusions • Three years after initiating PrEP, 60% of participants were still collecting drug (may over-estimate if stock-piling for the future) • The ongoing high rates of bacterial STIs in those attending confirmed that they needed PrEP • The reduction in HIV incidence was sustained and confirmed the very high adherence in this population and durable effectiveness of PrEP • The most likely reason for the HIV infections seen was the lack of PrEP at the time of exposure

14. Acknowledgements (1) PROUD Study participants MRC CTU at UCL Sarah Banbury, Liz Brodnicki, Christina Chung, Yolanda Collaco-Moraes, Monica Desai, David Dolling, David Dunn, Mitzy Gafos, Adam Gregory, Sajad Khan, Brendan Mauger, Sheena McCormack, Yinka Sowunmi, Ellen White, Gemma Wood HIV & STI Dept, Public Health England Monica Desai, Sarika Desai, Noel Gill, Anthony Nardone, GUMCAD team, HIV team Clinics Vanessa Apea (Barts Health NHS Trust), Christine Bowman & Claire Dewsnap (Sheffield Teaching Hospitals NHS Foundation Trust), Michael Brady (Kings College Hospital NHS Foundation Trust), Amanda Clarke & Martin Fisher (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 (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)

15. Acknowledgements (2) PROUD 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, Sonia Gupta, Jim Rooney, Murad Ruf University of Liverpool: SayeKhoo Independent Data Monitoring Committee: Anton Pozniak, Simon Collins, Fiona Lampe Community Engagement Group Community: YusefAzad (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, SonaliWayal, Will Nutland, Mitzy Gafos Advisors: Ingrid Young, Ford Hickson, Lisa McDaid, Marsha Rosengarten, Nicolas Lorente, AgataPacho, Elizabeth Poliquin, Anthony Nardone, Catherine Dodds, Adam Bourne, David Dolling, Sheena McCormack, Rob Horne

16. Change in receptive anal intercourse without a condom N = 199 187 161 140 171 144

17. Exit questionnaire

18. Distribution of follow-up (yrs)

19. PHE matching • Of 32 known HIV infections in PROUD, 29 were in the national dataset held by PHE • 2 diagnosed in PROUD in 2016 so likely reporting delay • 1 diagnosed in PROUD in July 2014 • One additional HIV infection (DEF) identified in PHE dataset and confirmed via clinic