1. Telling Time; Telling the Truth Engaging communities as stakeholders (and partners) in HIV vaccine R&D Mitchell Warren AVAC 2 July 2013 IAS Symposia Session: HIV Vaccines and Future Strategies

2. Where Do We Come From? What Are We? Where Are We Going? Paul Gauguin, 1897

3. DNA/Ad5 2010201120122013201420152016 1 234123412341234123412341234 Positive efficacy result No effect Regulatory submission/filing Planned Final results pending DPV ring Oral TDF/FTC Oral TDF Rectal TFV gel TFV gel TMC278 LA Injectable DNA/Ad5 TIMELINE LEGEND Pox-Protein HIV Prevention Options Timeline July 2013 * ** * Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/pxrd. ** Not all trials included are effectiveness trials. Trials included on this list are mainly phase II/IIb, III/IIIb and IV trials. Bangkok Tenofovir Study/CDC 4370 Partners PrEP Partners PrEP (no placebo) 2008 2005 2009 VOICE/MTN 003 Oral TDF/FTC Oral TDF iPrEx 2007 iPrEx Open-Label Extension (OLE) 2009 FEM-PrEP US FDA approval CAPRISA 004 2007 TDF2 Open-Label Extension TDF2/CDC 4940 TFV gel FACTS 001 Earliest regulatory submission VOICE/MTN 003 2009 MTN 017 Rectal TFV gel DPV Ring The Ring Study/IPM 027 ASPIRE/MTN 020 Earliest regulatory submission Possible LA Injectables TMC 278 LA Inject. Pox-Protein Various Phase I/II preliminary and bridging studies RV 144 2004 South Africa Licensure South Africa Research Thai Licensure 2009 HVTN 505 Additional demonstration projects & intermittent PrEP studies CAPRISA 008 FACTS 002 and other adolescent studies Various Phases of Long-Acting Injectables AVAC Report 2012: Achieving the End – One year and counting. www.avac.org/report2012

4. What We Said After Step in 2007* *...and after RV144 in 2009; 505 and Phambili in 2013  R&D is an iterative process  Every trial teaches us something  We need a wider variety of approaches in the pipeline  Vaccines take a long time to develop  Samples from the trial are a precious resource to help explain what happened with the vaccine  The field must take a deep breath, a step back and assess the implications  Proceed with discovery work that includes human clinical trials

5. What’s Past is Prologue  Large efficacy trials are possible and essential – and complex and unpredictable  It’s not the result as much as what we do with it o No matter what the headlines say, a single number is not the full result  No one trial answers all the questions o Just as no one product or approach is “the” answer for AIDS vaccines o Just as an AIDS vaccine is not “the” answer to ending the epidemic  It’s all incremental – no magic bullets

6. Where to from here  Mine trial data in every way possible, using the limited trial samples strategically and wisely  Continue the upstream scientific focus to develop better candidates that can build on current knowledge, fill gaps and get into trials  Think harder about new trial designs  Deliver what we have today for prevention & treatment

7. AIDS Vaccines 2013 and beyond  P5 – Pox-Protein Public-Private Partnership  Other products currently in clinical development  Replicating vectors  Translating NAb discoveries into vaccine candidates  Passive immunization and gene therapy studies  And how to engage a variety of communities and stakeholders in the inevitable ups and downs and uncertainties

8. What is “stakeholder engagement?”  Stakeholder engagement is not recruitment! (Recruitment is recruitment…)  It is a process of using the expertise stakeholders have to improve the research process and shape it together  It requires/benefits from improved research literacy amongst all stakeholders Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials, UNAIDS & AVAC, 2011, www.avac.org/gpp.

9. Now what?  Ensure preparedness efforts for “P5” trials are on track in Southern Africa and Thailand o Stakeholder dialogues; ongoing coordination with P5 partners; GPP work at proposed site levels o Publications and communications that address “what next”, “why so long” and clarity of changing timelines  Work to consensus on appropriate standard of care and prevention in proposed trials including P5, passive immunization trials and others  Sharpen and sustain messages about need for continued funding, state of the science and pipeline, and essential role of vaccine in long-term success at “ending AIDS”  Connect preventive vaccine agenda and advocacy with o Broader “ending AIDS” advocacy o Therapeutic vaccine and cure agendas and advocacy

10. COMBINE Demonstrate proven tools for immediate impact Daily oral TDF/FTC as PrEP 1% tenofovir gel Develop long-term solutions to end the epidemic AIDS vaccines Cure Multi-purpose prevention technologies Next generation ARV-based prevention Non-ARV-based microbicides Rectal microbicides Years to Impact Zero to 5 5 to 10 10 to End GOAL: A sustained decline in HIV infections (now at 2.5 million/year) Define and initiate the “core package” of PrEP demonstration projects Safeguard HIV Prevention Research Funding End confusion about “combination prevention” Narrow gaps in treatment cascade Prepare for new non-surgical male circumcision devices Testing Treatment Voluntary Medical Male Circumcision Female and male condoms Prevention of pediatric infection Syringe exchange programs Deliver proven tools for immediate impact AVAC Report 2012: Achieving the End – One year and counting. www.avac.org/report2012. Three-Part Agenda for Ending AIDS