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

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

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: 81-100) 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

Study Design Open-Label Prospective Cohort Study in the Paris Region http://prevenir.anrs.fr/ 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

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

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

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..

Dosing Regimen over Time

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)

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

Sexual Behavior Daily On Demand

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 (0.4-2.6) 6 1.2 (0.4-2.6) HAV 1 0.2 (0.0-1.3) 0.2 (0.0-1.1) HCV 3 0.7 (0.1-2.0) 4 0.8 (0.2-2.0) 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

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 (8.6-15.1) 91 (63) 12.5 (9.6 -15.9) 0.9 (0.6-1.4) 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 (2.1-5.9) 26 (24) 4.7 (3.0-7.1) 0.8 (0.4-1.5) Viral Hepatitis 6 (6) Neuro-psychiatric 11 (5) Treatment D/C due to drug-related AE 0 (0.0-0.8) 0 (0-0.7) .

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 (39.5-52.3) 204 40.3 (35.0-46.3) 1.1 (0.9-1.4) Grade 3 or 4 1 2.3 (0.1-12.6) 2.0 (0.1-11.0) (0.0-89.7) Grade 1 Creatinine (<1.5 ULN) 69 15.6 (12.1-19.7) 89 17.6 (14.1-21.7) 0.9 (0.6-1.2) Creat. Clearance [50-70[ ml/mn 67 15.1 (11.7-19.2)

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

PrEP “On Demand”

Acknowledgments The Participants The Sites Investigators and Counselors The Trial Scientific Committee The Community Advisory Board The ANRS Staff INSERM IPLESP http://prevenir.anrs.fr/ 17 17