Mitchell Warren AVAC 2 July 2013 IAS Symposia Session: HIV Vaccines and Future Strategies

1. Telling Time; Telling the TruthEngaging 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. HIV Prevention Options Timeline July 2013 *** Bangkok Tenofovir Study/CDC 4370 2005 Oral TDF TIMELINE LEGEND Oral TDF Partners PrEP Partners PrEP (no placebo) Oral TDF/FTC 2008 Positive efficacy result TFV gel 2009 VOICE/MTN 003 No effect Rectal TFV gel Oral TDF/FTC Regulatory submission/filing TDF2/CDC 4940 TDF2 Open-Label Extension DPV ring 2007 TMC278 LA Injectable iPrEx iPrEx Open-Label Extension (OLE) 2007 Planned FEM-PrEP DNA/Ad5 2009 Final results pending Additional demonstration projects & intermittent PrEP studies Pox-Protein US FDA approval CAPRISA 004 2007 TFV gel CAPRISA 008 VOICE/MTN 003 Earliest regulatory submission 2009 FACTS 001 Rectal TFV gel FACTS 002 and other adolescent studies DPV Ring MTN 017 Earliest regulatory submission ASPIRE/MTN 020 TMC 278 LA Inject. The Ring Study/IPM 027 Various Phases of Long-Acting Injectables Possible LA Injectables HVTN 505 DNA/Ad5 2009 South Africa Licensure RV 144 Pox-Protein 2004 South Africa Research Various Phase I/II preliminary and bridging studies Thai Licensure * 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. 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 • No matter what the headlines say, a single number is not the full result • No one trial answers all the questions • Just as no one product or approach is “the” answer for AIDS vaccines • 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 • Stakeholder dialogues; ongoing coordination with P5 partners; GPP work at proposed site levels • 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 • Broader “ending AIDS” advocacy • Therapeutic vaccine and cure agendas and advocacy

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