National ADAP TA Meeting Murray Penner and Natalie Cramer July 10, 2008

1. HIV Vaccine Research Update and NIAID HIV Vaccine Research Education Initiative (NHVREI) National ADAP TA MeetingMurray Penner and Natalie Cramer July 10, 2008

2. NASTAD NHVREI Activities • NASTAD’s involvement in HIV vaccine education • Overview of HIV vaccine development • Overview of the NASTAD NHVREI activities

3. Work in progress

4. Time between discovery of infectious agents and development of vaccines Source: Modified from H. Markel, NEJM, August 25, 2005

5. Vaccine research and development VACCINE DESIGN PRECLINICAL RESEARCH CLINICAL TRIALS DISCOVERY

6. Timeline for Efficacy Data From Current and Planned Vaccine Trials, 2007 2004 2005 2006 2007 2008 2009 2010 2011 2012 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 * RV 144 * HVTN 502 HVTN 503 * PAVE 100 * RV 144 HVTN 502 HVTN 503 PAVE 100 * Anticipated Data Availability

8. Timeline for Efficacy Data From Current and Planned Vaccine Trials 2004 2005 2006 2007 2008 2009 2010 2011 2012 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 * RV 144 STOPPED HVTN 502 STOPPED HVTN 503 PAVE 100 Under Construction ? RV 144 PAVE 100 * Anticipated Data Availability

9. Phase III Trial in Thailand (RV144) (with DoD, Thailand MOPH, HJF, Sanofi, VaxGen) • Canarypox + gp120 envelope protein boost • Completed immunization phase July 06 • N=16,000 volunteers • Now in follow-up phase • Continued DSMB oversight • Final results anticipated in 2009

10. STEP and Phambili • Suspended enrollment and study injections • Unblinded participants (Phambili, then STEP) • Counseled participants about possible increased risk of HIV infection • Continued follow up in both trials to assess vaccine effects

11. Summary of Recent Trials • Study design and execution provided earliest possible answer • Vaccine failed, not the trial • Animal models did not predict outcome in humans • More infections among vaccinees vs. placebo recipients • Why?  chance? due to vaccine? some other cause? • Increased risk of HIV infection among vaccinees most evident in uncircumcised men with pre-existing Ad5 immunity • No evidence of increased risk among vaccinees in circumcised men without pre-existing Ad5 immunity • Further studies underway to provide clues as to possible biological mechanisms

12. Current PAVE 100 Protocol Under Consideration • PAVE 100A • U.S. only • Circumcised, Ad5 seronegative MSM • Primary endpoints • Safety • HIV viral load post-infection • Secondary and exploratory

14. Information CycleIterative Process Forward Preclinical Research & Development Discovery Clinical Research

15. NASTAD NHVREI Activities (Year One) Provide an overview of HIV vaccine research and clinical trials in NASTAD Prevention Bulletin (March 2008). Conduct a special session during NASTAD Annual Meeting focusing on HIV vaccine research and clinical trials (May 2008). Highlight and promote HIV Vaccine Awareness Day (May 2008).

16. NASTAD NHVREI Activities (Year One) - continued Conduct a breakout session at National ADAP TA Meeting focusing on HIV vaccine research and clinical trials (July 2008). Conduct a brown-bag educational lunch for NASTAD staff focusing on HIV vaccine research and clinical trials (Summer 2008). Conduct a breakout session at National Viral Hepatitis TA Meeting focusing on HIV vaccine research and clinical trials (September 2008).

17. NASTAD NHVREI Activities (Year One) - continued Produce fact sheet for HDs designed to increase awareness of HIV vaccine research and clinical trials; highlight HD best practices (Fall 2008). Conduct a national TA conference call for HD staff to increase awareness and education of vaccine research and clinical trials (Fall 2008). Routinely distribute information regarding HIV vaccine research and clinical trials in existing publications (ongoing).

18. NASTAD NHVREI Activities (Year One) - continued Identify and participate in at least one conference (to be determined) and highlight HD efforts to increase awareness of HIV vaccine research and clinical trial participation (February 28, 2009).

19. NASTAD NHVREI (Year Two) andOngoing Activities Year Two Continue all activities from Year One. Conduct a national webinar on HIV Vaccine Awareness Day (May 2009). Ongoing Activities Program Reporting Evaluation activities Ongoing Training and TA for Project Staff

20. HIV Vaccine Research Contact Information For more detailed information about HIV vaccine research, please view the following websites: www.bethegeneration.org www.niaid.nih.gov/daids/vaccine www.hvtn.org www3.niaid.nih.gov/about/organization/vrc …or contact NIAID’s HIV Vaccine Trials Network at www.hvtn.org or AIDS Info at 1-800-448-0440 Para más información en el Español acerca de vacunas de SIDA, LLAME: 1-800-448-0440 (marque el número 2)

21. NASTAD Contact Information Murray C. Penner Deputy Executive Director, Domestic Programs mpenner@NASTAD.org Natalie O. Cramer Senior Manager, Prevention ncramer@NASTAD.org Joy Mbajah Manager, Prevention (and NHVREI Project Manager) jmbajah@NASTAD.org