1. Incidence of HIV-Infection with Daily or On Demand PrEP with TDF/FTC in the Paris Area: An Update of the Prevenir Study
JM. Molina, J. Ghosn, M. Algarte-Genin, D. Rojas -Castro, L. Beniguel, G. Pialoux, C. Delaugerre, J-P. Viard, C. Katlama, C. Segouin, C. Pintado, P-M. Girard, J. Lourenco, M. Ohayon, S. Le Mestre, B. Spire, V. Doré, L. Assoumou, and D. Costagliola for the ANRS Prevenir Study Group
Assistance Publique Hôpitaux de Paris, INSERM, Université de Paris, IPLESP, Coalition PLUS, AIDES, ANRS, SESSTIM, ORS PACA, France

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 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 in Paris like in San Francisco and Australia
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
eGFR > 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 regimen
Follow-up every 3 months with 4th Gen ELISA HIV test and plasma creatinine
STI screening at physician’s discretion (Guidelines recommend every 3 months in MSM)
Condoms, gels, risk reduction and adherence counseling, Q on sexual behavior
On peut changer en cours d’étude 4

5. Study Objectives Primary Objective
To show at 3 years > 15% reduction of new HIV diagnoses among MSM in Paris region in comparison with the numbers provided by the National Surveillance network in 2016
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 social disparities and 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%
May 2, 2019: 3,057 pts enrolled across 26 sites

6. Baseline Characteristics
Characteristics (Median, IQR) or (n, %)
N = 3057
Age (years)
36 (29-44)
Caucasian
2614 (85.5)
MSM
3013 (98.7)
Heterosexual men or women
30 (1.0)
Transgender
13 (0.4)
Bachelor’s degree
1863 (60.9)
Employed
2113 (69.1)
No regular sex partner
1681 (55.0)
History of PrEP use
1706 (55.8)
Use of Chemsex*
423 (13.8)
On Demand dosing regimen
1499 (49.2)
Nb condomless sex acts in prior 4 weeks
2 (0 - 5)
Nb sexual partners in prior 3 months
10 (5 - 20)
Mean duration of prior PrEP use 10 months
Incidence of study discontinuation: 9 per 100 PY
* at last sexual intercourse : cocaine, GHB, MDMA, mephedrone

7. Baseline Characteristics
Characteristics (Median, IQR) or (n, %)
Daily
N=1546
(50.8%)
On Demand
N=1499
(49.2%)
P-value
Age (years)
35 (28 – 43)
36 (30 – 44)
<.001
MSM
1513 (97.9)
1488 (99.3)
0.001
Heterosexual men or women
20 (1.3)
10 (0.7)
Transgender
12 (0.8)
1 (0.1)
Bachelor’s degree
902 (58.3)
958 (63.9)
0.004
Employed
1054 (68.2)
1057 (70.5)
0.660
No regular sex partner
870 (56.4)
803 (53.9)
0.165
History of PrEP use
844 (54.6)
858 (57.2)
0.142
Use of Chemsex*
218 (14.1)
204 (13.6)
0.715
No. condomless sex acts in prior 4 weeks
2 (0 – 6)
2 (0 – 4)
No. sexual partners in prior 3 months
12 (6 - 25)
10 (5 - 15)
Only 12 women (11 in daily and 1 in On demand); 18 heterosexual men (9 in daily and 9 in On demand)
* at last sexual intercourse : cocaine, GHB, MDMA, mephedrone..

8. Dosing Regimen over Time
Change between dosing regimen was allowed 15% change between visit half from daily to on demand and half from on demand to daily

9. Adherence to PrEP / Condoms
PrEP / Condom use at last sexual intercourse
7685 times people had sex assessed in 2134 participants > M3
(n, %)
Daily n = 3806 acts
On Demand n = 3879 acts
Total n= 7685
Total PrEP use
3705 (97.3)
3188 (82.2)
6893 (89.7)
Correct use*
3613 (97.5)
3072 (96.4)
6685 (97.0)
Suboptimal
92 (2.5)
116 (3.6)
208 (3.0)
No PrEP
101 (2.7)
691 (17.8)
792 (10.3)
Condoms
716 (18.8)
851 (21.9)
1567 (20.4)
* According to the protocol, or at least one pill before (<24h) and one pill after sex (<24h)

10. HIV Incidence (mITT Analysis)
Global HIV Incidence: 0.09/100 PY (95% CI: ) (2 cases)
Mean Follow-up of 8.7 months and 2208 Person-Years
Rate of study discontinuation: 8.9/100 PY
Treatment
Follow-Up
Pts-years
HIV Incidence
per 100 Pts-years
(95% CI)
P-value
TDF/FTC (Daily)
1072.9
0.0 ( 0.0 – 0.3 )
0.132
TDF/FTC (On Demand)
1132.7
0.2 ( 0.0 – 0.6 )
Incidence in Ipergay in Paris : 9,17/100 PY
143 HIV-infections averted*
* assuming an incidence of 6.6/100 PY as observed in the Placebo group of the ANRS Ipergay study 10 10

11. HIV-Infected individuals
Cases
Sex, Age
Date Started PrEP
Date Enrolled in PREVENIR
Last Neg. HIV Test
Positive HIV Tests
Comments
Case 1
MSM
52 y
April 2016
On demand
Feb 2, 2018
Sept 4, 2018
Jan 2, 2019
HIV serology: positive
Plasma : 6550 cp/mL
No RAMs to TDF/FTC
PrEP stopped 10 weeks before infection and condomless sex during this period
Case 2
47 y
June 2016
Daily
June 10, 2017
Dec 6, 2018
Feb 18, 2019
Plasma : > 106 cp/mL No RAMs to TDF/FTC
PrEP stopped 7 weeks before infection and condomless sex during this period

12. Sexual Behavior Numéro du poster de Luis: WEPED871
Increase of +43% at 3-month (P <0.001)
Increase of +21% at 3-month (P <0.001)
Decrease of -20% at 3-month (P <0.001)
Increase of +15% at 3-month (P <0.001)
Numéro du poster de Luis: WEPED871

13. Viral Hepatitis Infections
23 cases of viral hepatitis were diagnosed in 23 participants
Daily
Pts-years
On Demand
Pts-years
No.
Events
Incidence per 100 PY (95% CI)
No. Events
Incidence per 100 PY
(95% CI)
All Viral Hepatitis 10
0.9 (0.5–1.7) 13
1.2 (0.6–2.0)
HAV
0.0 (0–0.3) 1
0.1 (0–0.5)
HCV 9
0.8 (0.4–1.6) 11
1.0 (0.5–1.7)
HEV
HBV
Overall incidence rate of viral hepatitis
1.04 per 100 PY (0.66–1.56)

14. Incidence of Bacterial STIs
3026
2146
1701
1359
1001
674
Increase in incidence of +38% per year (P <0.001)
Any STI +38% per year (P<0.001); Any chlamydia +36% per year (P<0.001); Any Gonorrhoea +34% per year (P<0.001); Any mycoplasma +13% per year (P=0.453); Syphilis +120% (P<0.001)
Trends assessed in piecewise exponential survival models

15. Incidence of Bacterial STIs According to the PrEP Regimen
Overall incidence rate of 86 per 100 PY (95% CI 82-90)
Trends assessed in piecewise exponential survival models

16. Incidence of Anal CT/GC
Incidence of Anal Gonorrhoea
Increase of +47% per year (P <0.001)
Increase of +48% per year (P <0.001)
Overall incidence of 51 per 100 PY (95% CI 48-54)
Overall incidence of 27 per 100 PY (95% CI 24-29)
Trends assessed in piecewise exponential survival models

17. Adverse Events
Daily
Pts-years
On Demand
Pts-years
Incidence Rate Ratio
Daily vs On Demand
(95% CI)
No. Pts
Incidence per 100 PY
Drug-Related AEs
122
11.4
( 9.4–13.6)
150
13.2
( 11.2–15.5)
0.9
( 0.7–1.1)
Gastrointestinal 98
111
Asthenia 6 18
Cutaneous 5 7
Headache 8
Any Grade 3 or 4 AE 57
5.3
( 4.0–6.9) 50
4.4
( 3.3–5.8)
1.2
(0.8–1.8)
Infections 27 30
Neuro-psychiatric
Treatment D/C due to Drug-Related AE
0.0 (0–0.3) 3*
0.3 (0.0–0.8)
0.0 (0–2.6)
*Vomiting (grade 3); Diarrhea (grade 1); Nausea/Headache/Dizziness (grade 1)

18. Lab Abnormalities All Grades ALAT 139 13.0 (10.9–15.3) 117 10.3
Daily
Pts-years
On Demand
Pts-years
Incidence Rate Ratio
Daily vs On Demand
(95% CI)
No. Pts
Incidence per 100 PY
All Grades ALAT
139
13.0
(10.9–15.3)
117
10.3
(8.5–12.4)
1.3
(1.0–1.6)
Grade 3 or 4 9
0.8
(0.4–1.6) 7
0.6
(0.3–1.3)
1.4
( 0.4–4.3)
Grade 1 Creatinine
(>1.5 ULN)
165
15.4
(13.1 – 17.9)
177
15.6
(13.4–18.1)
1.0
(0.8–1.2)
Creat. Clearance
(50-70 ml/mn)
190
17.7
(15.3–20.4)
210
18.5
(16.1–21.2)
( 0.8 – 1.2)
<50 ml/mn
(0.4–1.5)
1.1
(0.4–3.0)

19. Summary
Interim report of an open-label cohort study enrolling mostly MSM: 50% use Daily, 50% On demand PrEP
Pts using Daily TDF/FTC have more partners, more condomless sex and a higher incidence of bacterial STIs
High efficacy of Daily and On Demand PrEP in MSM:
Only 2 HIV-infection in persons who have discontinued PrEP
High and correct use of PrEP
Good safety profile with both dosing regimens and only three participants with drug discontinuation due to gastro-intestinal AEs
High retention rate
High incidence of bacterial and viral STIs 19

21. Acknowledgments The Participants
The Sites Investigators and Counselors
The Trial Scientific Committee
The Community Advisory Board
The ANRS Staff
INSERM IPLESP
Paris Hospitals (APHP)
University of Paris 21 21