Presented by Mitzy Gafos behalf of the PROUD team httpwwwproudmrcacuk Clinical trial evidence for oral PrEP Effect size CI iPrEx daily Truvada MSM Americas Thailand South Africa ID: 1045061
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1. PROUD: Results and participant experiencesPresented by Mitzy Gafos, behalf of the PROUD teamhttp://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 PilotGMSM reporting condomless anal sex last/next 90days; 18+; and willing to take a pill every dayRisk reduction includes Truvada AFTER 12MRandomize HIV negative MSM(exclude if treatment for HBV/Truvada contra-indicated)Main endpoints in Pilot: recruitment and retentionFrom April 2014: HIV infection in first 12 monthsFollow 3 monthly for up to 24 monthsRisk reduction includes Truvada NOW
4. HIV IncidenceGroupNo. of infectionsFollow-up (PY)Incidence(per 100 PY)90% CIOverall23465.64.93.4–6.8Immediate3243.51.20.4–2.9Deferred20222.19.06.1–12.8Effectiveness =86% (90% CI: 64 – 96%)P value =0.0001Rate 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=0.47P=0.04Sexual Behaviour
6. STIsCaveatNumber of screens differed between the groups:e.g. Rectal gonorrhoea/chlamydia 974 in the IMM group and 749 in the DEFAdjusted OR=1.00, p=0.99
7. PROUD: In-depth InterviewsImmediate11 Deferred14Increased risk behaviourHIGH ADHERENCE6Same risk behaviourHIGH ADHERENCE3 Increased risk behaviour7 Increased risk behaviourLOW ADHERENCE1Same risk behaviourLOW ADHERENCE0 Same risk behaviour5 SPECIAL1SPECIAL2Purposeful Sampling: Risk-adherence matrix
8. Condom realitiesCondom usePleasureErectionIntimacySobrietyRisk takingNeverSometimesWant not to with partnerAttempt 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 positioningExclusiveAdditionalAlternativePartner typePartner statusPositioningEjaculationCondom 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 durationSeasons of riskUntil not sexually active, monogamous, married, children, bored of wild sex scene, deals with demonsOnly 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. SummaryHIV incidence – was much higher than expected in PROUD, despite high PEP useEffectiveness – 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 populationsSexual 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 behavioursPeriods – PrEP is perceived as an important additional prevention option for periods of riskOur 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 participantsMRC CTU at UCLSarah 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, PHEMonica Desai, Sarika Desai, Noel Gill, Anthony Nardone, GUMCAD team, HIV teamClinicsVanessa 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 CommitteeIndependent members: Mike Adler (Co-Chair), Gus Cairns (Co-Chair), Dan Clutterbuck, Rob Cookson, Claire Foreman, Stephen Nicholson, Tariq Sadiq, Matthew WilliamsInvestigator members: Brian Gazzard, Noel Gill, Anne Johnson, Sheena McCormack, Andrew Phillips Gilead: Matt Bosse, Rich Clarke, Jim Rooney, Murad RufUniversity of Liverpool: Saye KhooIndependent Data Monitoring Committee: Anton Pozniak, Simon Collins, Fiona LampeCommunity Engagement GroupCommunity: 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 SouthSocial Science Advisory GroupInterviewers: Caroline Rae, Gill Bell, Michael Rayment, Sonali Wayal, Will Nutland, Mitzy GafosAdvisors: 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. Ipergay : Event-Driven PrEP2 tablets (TDF/FTC or placebo) 2-24 hours before sex 1 tablet (TDF/FTC or placebo) 24 hours later1 tablet (TDF/FTC or placebo) 48 hours after first intake
16. mITT resultsGroupNo. of infectionsIncidence(per 100 PY)TDF/FTC20.94Placebo146.6Effectiveness =86% (95% CI: 40 – 99%)P value =0.002Number Needed to Treat =18Median number of pills/month (IQR): 16 pills (10-23) in the placebo arm16 pills (12-24) in the TDF/FTC arm (p=0.84)
17. Adherence by Pill CountMedian 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 PEP25 (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 100M1M2M4M6M8M10M12M14M16M18M20M22M24M26M28M30Visits] 0 - 4 ]] 4-11]]11-18]]18-25]]25-30]3823523152882361901621431281151059388726345N part..