Katharine Kripke, Ph.D.

Assistant Director, Vaccine Research Program, Division of AIDS, NIAID

AIDS Vaccine 2011 Journalist Training Program

September 11, 2011

 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 costeffective

True or false?
Participants might get HIV from the vaccine being tested. There is already an effective HIV vaccine, but its 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 highrisk behavior so that they get exposed to the virus.

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

Discovery

Preclinical Research & Development

Clinical Research

Vaccine trial process

Goals
Produce an immune response? Protect after viral challenge? Safe? Immune response?

Best dose? Safe? Magnitude/ types of immune response?

Does it work?

Preclinical Phase I Phase II Phase III

Animals

Participants

20-100 people

100-200 people

thousands of people

How do you know if a vaccine works?

Risk-reduction counseling

Vaccine is 75% effective

HIV-negative participants
Risk-reduction counseling

Slide courtesy of AVAC

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

Participants for HIV vaccine research

Participants should represent different: Sexes Races/Ethnicities Socioeconomic backgrounds Potential routes of transmission Environmental backgrounds HIV risk levels

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

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

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 doesnt mean they are HIV-infected

Frequency varies by vaccinecan be >80%

Durability: Potentially >10 years

We refer to this as Vaccine-Induced SeroPositivity, or VISP

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

HIV identified

VaxGen candidate fails in Phase III trials

True or false?
Participants might get HIV from the vaccine being tested. There is already an effective HIV vaccine, but its 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 highrisk behavior so that they get exposed to the virus.

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.

BeTheGeneration.NIH.gov

Vaccine efficacy trial plans, 2006

2003 2004 2005 2006 2007 2008 2009 2010 2011 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 Merck 023/HVTN 502 (STEP) HVTN 503 PAVE 100

Enrollment Follow-up

Anticipated Data Availability

PAVE 100

STEP RV 144

HVTN 503

Vaccine efficacy trials what really happened

2003 2004 2005 2006 2007 2008 2009 2010 2011 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 Merck 023/HVTN 502 (STEP)
HVTN 503

PAVE 100

Enrollment Follow-up

HVTN 503

HVTN 505

PAVE 100

STEP RV 144