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Efficacy of “On Demand” PrEP in the ANRS IPERGAY Open-Label Extension Study

Efficacy of “On Demand” PrEP in the ANRS IPERGAY Open-Label Extension Study.

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Efficacy of “On Demand” PrEP in the ANRS IPERGAY Open-Label Extension Study

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  1. Efficacy of “On Demand” PrEP in the ANRS IPERGAY Open-Label Extension Study JM. Molina, I. Charreau, B. Spire, L. Cotte, J. Chas, C. Capitant, C. Tremblay, D. Rojas-Castro, E. Cua, A. Pasquet, C. Bernaud, W. Rozenbaum, C. Delaugerre, V. Doré, S. Le Mestre, M.-C. Simon, J.-F. Delfraissy, L. Meyer and the ANRS IPERGAY Study Group Hospital Saint-Louis and University of Paris Diderot, Inserm SC10-US019 Villejuif, UMR912 SEAS Marseille, Hospital Croix-Rousse, Lyon,Hospital Tenon, Paris, APHP, CHUM, Montreal, Canada and AIDES, Paris, France

  2. Disclosures of Interest Research grants: Merck and Gilead Advisory Boards : BMS, Merck, Gilead, Jassen, ViiV Shareholder: none

  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) Trial was prematurely discontinued: overestimation of efficacy because of initial high adherence ? We do not have long-term safety data Open-label study extension pre-planned, and implemented only 8 days after the discontinuation of the placebo arm. All participants were offered to continue follow-up and access to open-label TDF/FTC

  4. Study Design TDF/FTC On Demand • HIV-negative MSM • Condomless anal sex with > 2 partners in prior 6 months • Creat. Clearance > 60 mL/mn • HbS Ag negative Placebo On Demand www.ipergay.fr Randomized Double-Blinded vs. Placebo then Open-Label Extension Nov 2014 Feb 2012 Jun 2016 TDF/FTC On Demand • Condoms, gels, tests for HIV (using 4th generation assays) and STIs, vaccinations for Hepatitis A and B, and peer counseling on risk reduction and adherence • Follow-up every two months

  5. IPERGAY : Sex-DriveniPrEP • 2 tablets 2-24 hours before sex • 1 tablet 24 hours later • 1 tablet 48 hours after first intake 4 pills of TDF/FTC taken over 3 days to cover one sexual intercourse

  6. IPERGAY : Sex-DriveniPrEP • 2 tablets 2-24 hours before sex • 1 tablet every day during sexual activity • 2 tablets after the last sexual intercourse On demand PrEP tells you How to Start and How to Stop PrEP

  7. KM Estimates of Time to HIV-1 Infection (mITT Population) 0.20 Log-rank test p=0.0022 0.18 0.16 0.14 Placebo 0.12 0.10 Probability of HIV Infection 0.08 0.06 TDF/FTC 0.04 0.02 0.00 months from D0 0 2 4 6 8 10 12 14 16 18 20 22 24 N at risk : Placebo 201 142 74 55 42 TDF/FTC 199 141 82 58 43 Medianfollow-up of 9.3 months: 16 subjectsinfected14 in placebo arm (incidence: 6.60 /100 PY) and 2 in TDF/FTC arm (0.91 /100PY) 86% relative reduction in the incidence of HIV-1 (95% CI : 40-98, p=0.002) NNT to avert one HIV-infection: 18 (95% CI: 11-50) Molina et al NEJM 2015

  8. Open Label Study ExtensionFlow Chart Screened n=445 Did not start PrEP n=45 HIV Infection VIH n=13 (3%) mITTAnalysis n=400 On FU Nov 2014 n=335 (84%) New Pts n=33 Non Eligible n=3 HIV Infection n=1 Declined n=3 (0.9%) Returned n=1 Started Open Label Extension n= 333 + 29 = 362 Pts Discontinued FU n=63 Consent w/o n=34 Lost FU n=16 Other n=13 Completed FU June 30, 2016 n= 299 (83%)

  9. OLE Baseline Characteristics * ecstasy, crack, cocaine, crystal, speed, GHB/GBL ** NG: Neisseria gonorrhoeae, CT: Chlamydia trachomatis, TP: Treponema pallidum, VH: viral hepatitis

  10. HIV Incidence (mITT Analysis) Median Follow-up in Open-Label Phase 18.4 months (IQR:17.5-19.1) 97% relative reduction vs. placebo

  11. HIV-1 Infection • A single HIV-infection during the Open-label Study Extension • Participant randomized in the TDF/FTC arm (double-blind phase) • Switch to the open-label extension 8 monthslater in November 2014 • HIV-1 infection diagnosed 40 dayslater in December 2014 • No PrEP use for months • Stable relationshipwith a single partner • TDF and FTC not detectableat time of HIV diagnosis • No drugresistance mutation • Antiretroviraltherapystarted 3 dayslater The stable partner was also found to be HIV-1 infected….

  12. Adherence by Pill Count Median Nb pills/month: 18 (IQR: 11-25)

  13. Adherence by Questionnaires PrEP use at the last sexual intercourse Double-blind phase: 1193 Q Open-Label Phase: 1617 Q *At least one pill before and one pill after

  14. Adherence by Plasma TFV Levels OLE Blinded 100% 90% 80% 71% 69% ]1-10] ng/mL 70% 7% 9% ]10-40] ng/mL 9% 60% > 40 ng/mL 14% Percentage of participants 55% 50% 46% 40% 30% 20% 10% 0% All visits* M6 N samples 1516 336 N participants 199 336

  15. Adverse Events **Decrease in plasma creatinine clearance to 48, 71 and 76 ml/mn

  16. Lab Abnormalities 8 participants with creatinine clearance < 60 ml/mn at least once (2 double-blind and 7 Open-label)

  17. SexualBehavior Proportion Pts with Condomless Sex for Last Receptive Anal Intercourse P for Trend = 0.0003 Double blinded D0 • No significant change in median Nb of partners or sexualactsduring the open-label phase (P= 0.42 and P= 0.12)

  18. SexuallyTransmitted Infections Incidence rate of first STI 35.2 vs 40.6 per 100 PY in the double-blinded and OLE phases

  19. Summary On Demand PrEP with oral TDF/FTC remained highly effective in high risk MSM as long as it was taken Safety of On Demand PrEP was good Low condom use in the open-label phase did not undermine efficacy No significant change in Nb partners or sex acts High rate of STIs needs to be addressed PrEP improved pleasure and removed fear during sexual activity Results of this study have led to PrEP approval in France with full reimbursement

  20. PrEP “On Demand”

  21. BE SURE TO ATTEND!!! More on PrEP On Demand at Durban • Luis Sagaon Teyssier: Reported changes in PrEP and Condom use in MSM during the Open-label extension of the ANRS Ipergay study (Wednesday July 20, 12:30-14:30 Poster WEPEC 263) • Isabelle Durand Zaleski: Cost-effectiveness of on Demand PrEP in MSM in the ANRS Ipergay study (Thursday July 21, Cost-Effectiveness and Modeling, Session Room 2: 16:30-18:30) • PrEP Roll-out in France (Wednesday July 20, From Clinical Trials to Clinical Care, Session Room 7, 14:30-17:00)

  22. Acknowledgments The Participants The Study Staff and Peer-Counselors The Trial Scientific Committee The DSMB The Community Advisory Board The ANRS Staff INSERM SC10

  23. Community Engagement

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