Setting the Stage for PrEP Where are we now, and where should we go? Mitchell Warren, Executive Director PrEP in Practice Satellite @ AIDS 2018 25 July 2018

To Think About Where is the greatest unmet need for prevention? What products will people want AND use? How can we best deliver PrEP for impact AND build platforms to deliver next generation PrEP?

Oral PrEP Timeline US FDA approval & WHO guidance 2010 2011 2012 2013 2014 2015 2016 2017 2018 iPrEx results US FDA approval & WHO guidance Gates demo projects start in Kenya, Uganda, South Africa, Senegal, Benin, India, Nigeria enrolling avg. 700 participants per project Gates Planning & Feasibility Studies Partners OLE results PROUD & IPERGAY results WHO recommends PrEP as option for all at substantial risk ~24 countries have approved PrEP Partners PrEP & TDF2 results Kenya approves PrEP Bridge to Scale Implementation Project (Jilinde Project) in Kenya aiming to enroll 20,000 Research (clinical trials; OLE) VOICE & FEM-PrEP oral arms stop early Regulatory/country approvals South Africa approves PrEP DREAMS starts to implement PrEP in 5 countries Implementation/demo Selection of implementation and demo projects, 152 projects in total. For full list see www.avac.org/sites/default/files/resource-files/ongoing_planned_oral_PrEP_studies_Oct2017.pdf

Where Are We Now 43 regulatory approvals 2 global guidelines 13 national guidelines 141 discrete oral PrEP projects worldwide – demo projects, national rollout, DREAMS Initiative implementers Approximately 340,000 oral PrEP initiations Of which 220,000 are in the US As of July 2018, from https://www.prepwatch.org/country-updates/

What We’ve Learned 131 68 54 Oral PrEP Implementation Studies Key Takeaways from early Oral PrEP rollout Distinct post-approval oral PrEP implementation projects and studies; most were small-scale 131 Post-approval studies and projects Post-approval studies were not all designed to address decision-maker questions Different countries conducted projects including multiple in the same country (e.g. 25 in one country) 68 Countries Data from research was not well timed to inform decision making at global or country level Different organizations involved in oral PrEP implementation research 54 Stakeholders Complex, fragmented stakeholder landscape

Why It Matters Different Strokes for Different Folks Method Contraception HIV Prevention Behaviour ✓ Barrier Methods Gels ✓– not registered Rings ✓– with regulatory body Oral pill Injectables ? – 1 ARV, 1 bNAb, 2 vax in phase 3; others in development Implants ? – multiple in preclinical Surgical procedures Treatment

Key Questions about Users (& Influencers) Personal Programmatic Policy Who needs what? Who wants what? Who gets what? How to deliver it? How to support adherence? Who pays? Who decides? Those who use Those who choose Those who pay the dues

Product Considerations For each product, understand and balance: Biologic efficacy Product cost User effectiveness Program cost Dosing User preference Side effect profile Provider training User burden Systemic/Topical Health system burden Reversibility Delivery channel(s) Discretion of use/ contribution of stigma User vs. provider initiated

Bottom line(s) Oral TDF/FTC is the PrEP we have now Oral F/TAF results due in 2020 – BUT currently only being studied for efficacy in men and transgender women who have sex with men Dapivirine ring could enter the market by 2020 – possible multi-purpose product could follow Fast Track targets (90-90-90+++) due in 2020 Earliest injectable px to market in 2022 – one possible product Earliest vax or bNAb to market in 2024 – multiple products Earliest implant px to market in 2025 – multiple devices; two active drugs Fast Track targets (95-95-95+++) due in 2030

Acknowledgements