PROUD: Results and participant experiences

Presented by Mitzy Gafos, behalf of the PROUD team

http://www.proud.mrc.ac.uk/

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

PROUD PilotGMSM 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 retentionFrom April 2014: HIV infection in first 12 months

Follow 3 monthly for up to 24 months

Risk reduction includes Truvada NOW

HIV IncidenceGroup No. of

infectionsFollow-up

(PY)Incidence

(per 100 PY)90% CI

Overall 23 465.6 4.9 3.4–6.8

Immediate 3 243.5 1.2 0.4–2.9

Deferred 20 222.1 9.0 6.1–12.8Effectiveness =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

0

10

20

30

40

Per

cent

age

0 1 2-4 5-9 10-19 20+

All partners

0

10

20

30

40

Per

cent

age

0 1 2-4 5-9 10-19 20+

All partners

0

10

20

30

40

Per

cent

age

0 1 2-4 5-9 10-19 20+

Participant receptive, no condom

0

10

20

30

40

Per

cent

age

0 1 2-4 5-9 10-19 20+

Participant receptive, no condom

Baseline 12 months

Immediate Deferred

P=0.47

P=0.04

Sexual Behaviour

STIs

Any STI

Gonorrh

oea

Chlamydi

a

Syphili

s

Rectal G

C/CT0

10

20

30

40

50

60 p=0.08

p=0.44

p=0.08

p=0.32

p=0.44

ImmediateDeferred

CaveatNumber 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

PROUD: In-depth Interviews

Immediate11 

Deferred14

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

Condom realities

Condom use

PleasureErectionIntimacySobriety

Risk taking

Never Sometimes 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

PrEP positioningExclusive

Additional

Alternative

Partner type

Partner status

Positioning

Ejaculation

Cond

om u

se “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”

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”

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 ”

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.

Acknowledgements (1)

Study participants

MRC 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 team

ClinicsVanessa 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)

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 Williams

Investigator 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

Friday Saturday Sunday Monday Tuesday Wednesday Thursday Friday Saturday Sunday

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

mITT results

Group No. of infections

Incidence(per 100 PY)

TDF/FTC 2 0.94Placebo 14 6.6

Effectiveness =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 arm• 16 pills (12-24) in the TDF/FTC arm (p=0.84)

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 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%)Perc

enta

ge o

f par

ticip

ants

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