Katharine Kripke, Ph.D.

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

AIDS Vaccine 2011 Journalist Training ProgramSeptember 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 cost-effective

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.

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

DiscoveryPreclinical Research &

Development

Clinical Research

Vaccine trial process

Preclinical Phase I Phase II Phase III

Participants

Goals

Animals

20-100 people 100-200

peoplethousands of people

•Produce an immune response?•Protect after viral challenge?

•Safe?•Immune response?

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

•Does it work?

HIV-negative participants HIV-negative participants

vaccine

placebo

Risk-reduction counseling

Risk-reduction counseling

Vaccine is 75%

effective

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 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

Results of Phase III Thai Trial (RV144)

HVTN 505 enrollment

begins

1980 1990 2000 2010

First HIV vaccine

trial opens Phase II Step and Phambili studies halted

VaxGen candidate fails

in Phase III trials

HIV identified

?

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.

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

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Enrollment Follow-up

ST

EP

RV

144

HV

TN

503

PA

VE

100

2003

Anticipated Data Availability

HVTN 503

PAVE 100

RV 144

Merck 023/HVTN 502 (STEP)

2004 2005 2006 20112007 2008 2009 2010

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

HVTN 503

PAVE 100

Enrollment Follow-up ST

EP

RV

144

HV

TN

503

PA

VE

100

RV 144

Merck 023/HVTN 502 (STEP)

HVTN 505

20112007 2008 2009 20102003 2004 2005 2006