Dr Sheena McCormack - European ChemSex Forum 2016, London

1. PrEP and ChemSex
– looking forward
Sheena McCormack
MRC Clinical Trials Unit at UCL
56 Dean Street

2. What is PrEP?
 Drug given to HIV uninfected
individuals before exposure to
HIV
 Currently tenofovir or Truvada
 Currently tablets taken daily or
before and after sex

3. The plan
 Scene setting
 PrEP works, but we needed 2
more trials in Europe
 PrEP and ChemSex

5. HIV infections diagnosed among MSM in Europe have
increased during the last decade
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Numberofdiagnosedcases
Year of diagnosis
Men who have sex with men
Heterosexual cases,
excluding cases from
countries with generalised
HIV epidemics
Heterosexual cases from
countries with generalised
HIV epidemics
Injecting drug use
+33%
-61%
-36%
ECDC/WHO (2014). HIV/AIDS Surveillance in Europe, 2013.
-14%

6. Hughes and Field, Future Microbiol, (2015) 10(1), 35-51
STI diagnoses in MSM in England

7. STIs by HIV status in MSM in England
Malek, Mitchell et al Euro Surveill. 2015;20(15):pii=21093.
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21093

8.  2010: iPrEX reports modest benefit
with daily Truvada for gay men and
transgender women
 2011: Partners PrEP report large
benefit with daily tenofovir or Truvada
in heterosexuals
 2012: IPERGAY and PROUD start
PrEP timeline

9. PROUD Pilot
GMSM reporting AI no condom 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)
McCormack, Dunn et al, Lancet, 09 September 2015
Follow 3 monthly for HIV and STIs up to 24 months
Risk reduction includes
Truvada NOW

10. Study Design
•HIV negative high risk MSM
•Condomless anal sex
with > 2 partners within 6 m
•eGFR > 60 mL/mn
Full prevention services*
TDF/FTC before and after sex
Full prevention services*
Placebo before and after sex
* Counseling, condoms and gels, testing and treatment for STIs, vaccination for HBV and HAV, PEP
 End-point driven study : with 64 HIV-1 infections, 80% power to detect a 50% relative
decrease in HIV-1 incidence with TDF/FTC (expected incidence: 3/100 PY with placebo)
 Follow-up visits: month 1, 2 and every two months thereafter
Double-Blinded Randomized Placebo-Controlled Trial
www.ipergay.fr

11. Friday Saturday Sunday Monday Tuesday Wednesday Thursday Friday Saturday Sunday
Ipergay : Event-Driven iPrEP
 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

12. HIV Incidence
Group No. of
infections
Follow-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 6.1–12.8
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)

13. KM Estimates of Time to
HIV-1 Infection (mITT Population)
Mean follow-up of 13 months: 16 subjects infected
14 in placebo arm (incidence: 6.6 per 100 PY), 2 in TDF/FTC arm (incidence: 0.94 per 100 PY)
86% relative reduction in the incidence of HIV-1 (95% CI: 40-99, p=0.002)
NNT for one year to prevent one infection : 18

14. Conclusions
 HIV incidence – was much higher than
expected in both trials
 Despite extensive use of PEP in PROUD (174
courses for 85(31%) of DEF participants)
 Effectiveness – was greater in the real world
than preceding placebo controlled trials, and the
IPERGAY instruction worked just as well as daily
 Other STIs – were no greater in those on PrEP
or not on PrEP in PROUD; very common in both
study populations

15. Europe’s response to 2 trials
 ECDC updated statement
 Cost-effectiveness and
 Appropriate models of care and access to be
addressed in Member States
 EACS draft guidelines
 Daily for MSM and others
 Event-based for MSM
 Demonstration projects/national policies
 Amsterdam, then Antwerp started
 Several countries working on national policy
 France approved a programme (January 2016);
NHS England has not

17.  January 2015, 182 PEPSE scripts
 76/182 (42%) reported ChemSex
 49/182 (27%) reported group sex (≥2)
 ChemSex and group sex
 37/76 (49%) on Chems reported group sex
 37/49 (76%) having group sex on Chems
PEP and ChemSex in Dean St1
1Nektarios Antoniou (personal communication)

18.  Rectal sexually transmitted infections
(gonorrhoea and chlamydia)
 ≥2 partners in the last 3 months
Explain majority of HIV seroconversions
 ChemSex in the last 3 months
Explain all HIV seroconversions
 PEP in the last year
Drivers of HIV in PROUD1
1Lancet letters, 08 April 2016

19.  G/meph/crystal before starting PrEP
 231(44%)/525 Nov12-Apr141
 G/meph/crystal during PrEP
 187(46%)/408 – 56(14%)/408 injecting
Sep2015 extract2
 212(51%)/417 - 74(18%)/417 injecting
Mar2016 extract2
PrEP and ChemSex in PROUD
1Dolling D et al Trials, Mar2016
2Ellen White (personal communication)

20. Drug use in last 3 months Immediate Deferred
Mephedrone 35% 38%
GHB/GBL (liquid ecstasy) 32% 30%
Crystal meth (methamphetamine) 19% 17%
Poppers (amyl nitrate) 49% 49%
Viagra 44% 39%
Cocaine (coke) 26% 25%
Cannabis (marijuana, grass) 24% 24%
Ecstasy (E) 15% 18%
Ketamine (K) 18% 15%
Other 8% 5%
Speed (amphetamine) 6% 4%
Anabolic steroids 4% 3%
Baseline demographics

21. Adherence and ChemSex

22. Adherence Assessed by CASIs
PrEP use during the last sexual intercourse
1212 sexual intercourses assessed in 319 participants
% PrEP Use
(min-max)
TDF/FTC
n = 649 acts
Placebo
n = 563 acts
Total
% (min-max)
Correct use* 45 (36-57) 40 (22-49) 43 (35-51)
Suboptimal use 27 (14-35) 31 (18-44) 29 (20-38)
No PrEP 27 (15-37) 29 (24-44) 28 (20-38)
* According to the protocol, or at least one pill before and one pill after sex

23. Friday Saturday Sunday Monday Tuesday Wednesday Thursday Friday Saturday Sunday
Ipergay : Event-Driven iPrEP
 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

24. Concluding thoughts
 Overwhelming evidence that PrEP adds benefit -
even to a very high standard of prevention
 Overwhelming evidence of need in a sub-
population of MSM in Europe
 We need to better understand ChemSex motivations
and behaviours to identify those that need
additional support – it’s certainly not all

25. Participant Voices

26. STIs
p=0.08
p=0.44
p=0.08
p=0.32
p=0.44
0
10
20
30
40
50
60
Immediate
Deferred
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

27. Adherence by Pill Count
4.00 0 or missing
]1 – 4]
2.00 ]4 – 11]
3.00 ]11 – 18]
4.00 ]18 – 25]
]25 – 30]
TDF/FTC
Nb pills/month
Placebo
Nb pills/month
4.00 0 or missing
]1 – 4]
2.00 ]4 – 11]
3.00 ]11 – 18]
4.00 ]18 – 25]
]25 – 30]