HIV Vaccine Clinical Trial Participation

1. HIV Vaccine Clinical Trial Participation Katharine Kripke, Ph.D. Assistant Director, Vaccine Research Program, Division of AIDS, NIAID AIDS Vaccine 2011 Journalist Training Program September 11, 2011

3. Scaling up treatment is essential • Scaling up other prevention interventions is essential • Even with ART decreasing transmission by 96%, people are most infectious in the first weeks after infection, when they are least likely to be on ART • Circumcision is ~60% effective and only protects ♂ • Other prevention interventions (condoms, needle exchange, microbicides, PrEP) are highly dependent on adherence • A highly effective vaccine would be less of a burden on individuals than lifelong treatment or behaviorally dependent prevention • Even a partially effective vaccine would be cost-effective

4. True or false? • Participants might get HIV from the vaccine being tested. • There is already an effective HIV vaccine, but it’s being deliberately withheld. • Vaccines are intended to cure people with HIV. • If someone volunteers in an HIV vaccine trial, it means they have HIV. • Researchers test HIV vaccines by administering the vaccine and then exposing the participants to the virus. • Researchers try to get participants to engage in high-risk behavior so that they get exposed to the virus.

5. What is an ideal vaccine? • Effective (>90%) • Protects against different subtypes of HIV • One vaccine for all subtypes, or different vaccines tailored to different subtypes? • Protects against different routes of infection (vaginal, anal, blood) • Can be manufactured to scale • Protects diverse people (sex, geography, genetics, behavior) • As few vaccinations per person as possible • Affordable • Acceptable

6. Preclinical Research & Development Clinical Research Discovery

7. Vaccine trial process • Best dose? • Safe? • Magnitude/ types of immune response? Goals • Does it work? • Produce an immune response? • Protect after viral challenge? • Safe? • Immune response? Preclinical  Phase I  Phase II  Phase III Animals 20-100 people Participants 100-200 people thousands of people

8. How do you know if a vaccine works? Risk-reduction counseling vaccine Vaccine is 75% effective placebo HIV-negative participants HIV-negative participants Risk-reduction counseling

9. Slide courtesy of AVAC

10. Research Safety & Ethics • Government regulation (FDA in US) • Protocols • Independent expert review/oversight • Community Advisory Boards • Informed consent process • Consent form • Explanation of risks • Free to leave study • Reporting results

11. Participants for HIV vaccine research • Participants should represent different: • Sexes • Races/Ethnicities • Socioeconomic backgrounds • Potential routes of transmission • Environmental backgrounds • HIV risk levels

12. Risks of Participation • Like most vaccines, the HIV vaccines used in clinical trials may cause side effects, such as: • Soreness at the injection site • Low-grade fever • Body aches • Side effects tend to go away quickly on their own • No long term side effects have been identified in HIV vaccines tested to date

13. Risk behavior in trials • Participants in clinical trials are continually counseled on how to reduce the risk of being exposed to HIV infection • No evidence that participation in HIV vaccine research leads individuals to engage in behaviors that increase their HIV risk • Data from several trials completed to date shows that risk behaviors usually decline overall, particularly during the vaccination period when study visits are more frequent

14. Vaccine-induced seropositivity • HIV vaccines are designed to provoke immune responses – this includes antibody production • Standard tests for HIV detect antibodies, not virus • Study participants who receive HIV vaccines will often test positive (seropositive) on these standard tests but it doesn’t mean they are HIV-infected • Frequency varies by vaccine—can be >80% • Durability: Potentially >10 years • We refer to this as Vaccine-Induced SeroPositivity, or VISP

15. Key clinical trial milestones: HIV vaccine research HVTN 505 enrollment begins First HIV vaccine trial opens Results of Phase III Thai Trial (RV144) Phase II Step and Phambili studies halted 1980 1990 2000 ? 2010 VaxGen candidate fails in Phase III trials HIV identified

16. True or false? • Participants might get HIV from the vaccine being tested. • There is already an effective HIV vaccine, but it’s being deliberately withheld. • Vaccines are intended to cure people with HIV. • If someone volunteers in an HIV vaccine trial, it means they have HIV. • Researchers test HIV vaccines by administering the vaccine and then exposing the participants to the virus. • Researchers try to get participants to engage in high-risk behavior so that they get exposed to the virus.

17. How people can help find an HIV vaccine: • Educate themselves and others about HIV vaccine research – visit http://bethegeneration.nih.gov. • Talk to friends and family members about HIV vaccine research. • Talk about HIV prevention. • Volunteer for an HIV/AIDS vaccine trial. • Be supportive of trial volunteers. • Visit www.hvtn.org to find a local vaccine trial site & participate in a Community Advisory Board.

18. Thank You! BeTheGeneration.NIH.gov

19. BACKUP SLIDES

20. Vaccine efficacy trial plans, 2006

21. Vaccine efficacy trials – what really happened