1. 22th International AIDS Conference
Incidence of HIV-infection in the ANRS Prevenir Study in the Paris Region with Daily or On Demand PrEP with TDF/FTC
J.-M. Molina, J. Ghosn, L. Béniguel, D. Rojas-Castro, M. Algarte-Genin, G. Pialoux, C. Delaugerre, Y. Yazdanpanah, C. Katlama, C. Ségouin, S. Morel, C. Pintado, B. Loze, S. Le Mestre, S. Gibowski, V. Doré, L. Assoumou, B. Spire, D. Costagliola, and the Prevenir ANRS study group
Assistance Publique Hôpitaux de Paris, INSERM, Sorbonne University, IPLESP, Coalition PLUS, AIDES, ANRS,
SESSTIM, ORS PACA, France
22th International AIDS Conference
Amsterdam, July 25, 2018 1

2. Disclosures Research grants: Gilead
Advisory Boards : Merck, Gilead, ViiV, Teva
Shareholder: none 2

3. Background
ANRS IPERGAY: high effectiveness of PrEP with oral TDF/FTC taken « On Demand » in high risk MSM.
86% relative reduction in HIV-incidence in the TDF/FTC arm vs placebo (95% CI: 40-98, P=0.002)
97% relative reduction in HIV-incidence in the TDF/FTC arm vs placebo during the open-label extension (95% CI: )
Limited data on real-world experience with On demand PrEP
Confirm public health impact of PrEP on the HIV epidemic like in San Francisco and New South Wales
Molina et al. NEJM 2015, Lancet HIV 2017

4. Study Design Open-Label Prospective Cohort Study in the Paris Region
Open-Label Prospective Cohort Study in the Paris Region
n = 3,000
May 3rd 2017
May 31st 2020
HIV-negative high risk adults
Inconsistent Condom use
Creat. Clearance > 50 mL/mn
HbS Ag negative if On Demand
TDF/FTC
Daily
On Demand
Show 15% reduction in new HIV diagnoses among MSM in the Paris Region
Participants opted for either Daily or On Demand PrEP and could switch regimens
Follow-up every 3 months with 4th Gen ELISA HIV test and plasma creatinine
STI screening at physicians’ discretion (Guidelines recommend every 3 months in MSM)
Condoms, gels, risk reduction and adherence counseling, Q on sexual behavior 4

5. Study Objectives Primary Objective
To show > 15% reduction of new HIV diagnoses among MSM in the Paris region in comparison with the numbers provided by the National Surveillance network in 2016 (mandatory notification of HIV diagnoses in France)
Secondary Objectives
Participants characteristics
Overall HIV incidence and by dosing regimen (Daily or On Demand)
PrEP adherence and coverage of sex events (self-report, dried blood spots)
Impact of peer counseling on adherence and retention
Sexual behavior (condom use, Nb of sexual acts, Nb of partners, STIs)
Safety, tolerability
3,000 pts to be enrolled (85% MSM) with the hypothesis of PrEP efficacy: 80%
July 2, 2018: 1628 pts enrolled across 22 sites

6. Baseline Characteristics
Characteristics (Median, IQR) or (n, %)
N = 1628
Age (years)
36 (30-44)
Caucasian
1385 (85.2)
MSM
1607 (98.8)
Heterosexual men or women
12 (0.8)
Transgender
8 (0.5)
No regular sex partner
839 (51.7)
History of PrEP use
930 (57.2)
Use of Chemsex*
257 (15.8)
Slam (drug injection during sexual intercourse)
26 (1.6)
On Demand dosing regimen
870 (54.6)
Nb condomless sex acts in prior 4 weeks
2 (0-5)
Nb sexual partners in prior 3 months
10 (6-20)
* at last sexual intercourse : cocaine, GHB, MDMA, mephedrone

7. Baseline Characteristics
Characteristics (Median, IQR) or (n, %)
Daily
n = 724 (45.4%)
On Demand
n= 870 (54.6%)
P-value
Age (years)
36 (30-44)
0.10
MSM
708 (98)
865 (99.4)
Heterosexual men or women
7 (0.1)
5 (0.6)
<.01
Transgender
8 (1.1)
0 (0)
No regular sex partner
380 (53)
437 (51)
0.41
History of PrEP use
408 (56.5)
515 (59.2)
0.28
Use of Chemsex*
128 (17.7)
124 (14.3)
0.06
No. condomless sex acts in prior 4 weeks
3 (1-8)
2 (0-4)
<.001
No. sexual partners in prior 3 months
15 (7-25)
10 (5-15)
* at last sexual intercourse : cocaine, GHB, MDMA, mephedrone..

8. Dosing Regimen over Time

9. Adherence to PrEP / Condoms
PrEP / Condom use at last sexual intercourse
2279 sex acts assessed in 1102 participants > M3
(n, %)
Daily n = 1088 acts
On Demand n = 1191 acts
Total n= 2279
Total PrEP use
1068 (98.2)
967 (81.2)
2035 (89.2)
Correct use*
1024 (95.8)
931 (96.2)
1955 (96.1)
Suboptimal
44 (4.1)
36 (3.7)
80 (3.9)
No PrEP
20 (1.8)
224 (18.8)
244 (10.7)
Condoms
206 (18.9)
258 (21.6)
464 (20.4)
* According to the protocol, or at least one pill before (<24h) and one pill after sex (<24h)

10. HIV Incidence (ITT Analysis)
Treatment
Follow-Up
Pts-years
HIV Incidence
per 100 Pts-years
(95% CI)
TDF/FTC (Daily)
443
0 (0-0.8)
TDF/FTC (On Demand)
506
0 (0-0.7)
Mean Follow-up in this Open-Label Study: 7 months (SD: 4)
Incidence of study discontinuation:
3.3/100 PY including 1.5/100 PY who discontinued PrEP
85 HIV-infections averted*
* assuming an incidence of 9.17/100 PY as observed in the ANRS Ipergay study in Paris 10 10

11. Sexual Behavior
Daily
On Demand

12. Viral Hepatitis Infections
11 cases of viral hepatitis were diagnosed in 11 participants
Daily
443 Pts-years
On Demand
506 Pts-years
No. Events
Incidence per 100 PY (95% CI)
Bacterial STIs
Pending
All Viral Hepatitis 5
1.1 ( ) 6
1.2 ( )
HAV 1
0.2 ( )
0.2 ( )
HCV 3
0.7 ( ) 4
0.8 ( )
HEV
HBV
0 (0-0.8)
0 (0-0.7)
Incidence rate of first Viral Hepatitis
1.1 vs 1.2 per 100 PY in the Daily and On Demand groups

13. Incidence per 100 Pts-years
Adverse Events
Daily
443 Pts-years
On Demand
506 Pts-years
Incidence rate ratio
(95% CI)
No. Events (Nb pts)
Incidence per 100 Pts-years
No. Events
(Nb pts)
Drug-Related AEs 75
(51)
11.5
( ) 91
(63)
12.5
( )
0.9
( )
Gastrointestinal
52 (40)
62 (48)
Asthenia
7 (6)
7 (7)
Cutaneous
3 (2)
5 (5)
Headache
3 (3)
Any Grade 3 or 4 AE 24
(16)
3.6
( ) 26
(24)
4.7
( )
0.8
( )
Viral Hepatitis
6 (6)
Neuro-psychiatric
11 (5)
Treatment D/C due to drug-related AE
0 ( )
0 (0-0.7) .

14. Incidence per 100 Pts-years
Lab Abnormalities
Daily
443 Pts-years
On Demand
506 Pts-years
Incidence rate ratio
(95% CI)
Nb of first events
Incidence per 100 Pts-years
All Grades ALAT
202
45.6
( )
204
40.3
( )
1.1
( )
Grade 3 or 4 1
2.3
( )
2.0
( )
( )
Grade 1 Creatinine
(<1.5 ULN) 69
15.6
( ) 89
17.6
( )
0.9
( )
Creat. Clearance [50-70[ ml/mn 67
15.1
( )

15. Summary
Interim report of an open-label cohort study enrolling mostly MSM
High efficacy of Daily and On Demand PrEP in MSM: No breakthrough HIV-infection and 85 HIV-infections averted
Pts using Daily TDF/FTC have more partners and more frequent sex
High and correct use of PrEP
Good safety profile with both dosing regimens and no drug discontinuation for AEs
High retention rate
Trend toward some increase in risk compensation
Data on STIs rates and HIV epidemic are pending 15

16. PrEP “On Demand”

17. Acknowledgments The Participants
The Sites Investigators and Counselors
The Trial Scientific Committee
The Community Advisory Board
The ANRS Staff
INSERM IPLESP 17 17