HIV Vaccine Clinical Trials Participation (Katharine Kripke)

8/4/2019 HIV Vaccine Clinical Trials Participation (Katharine Kripke)

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Katharine Kripke, Ph.D.

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

AIDS Vaccine 2011 Journalist Training Program

September 11, 2011


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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 afterinfection, 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 dependenton adherence

A highly effective vaccine would be less of a burdenon individuals than lifelong treatment or behaviorallydependent prevention

Even a partially effective vaccine would be cost-effective


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True or false?

Participants might get HIV from the vaccine beingtested.

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, itmeans they have HIV.

Researchers test HIV vaccines by administering the

vaccine and then exposing the participants to thevirus.

Researchers try to get participants to engage in high-risk behavior so that they get exposed to the virus.


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What is an ideal vaccine?

Effective (>90%)

Protects against different subtypes of HIV

One vaccine for all subtypes, or different vaccinestailored 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


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Discovery PreclinicalResearch &Development

ClinicalResearch


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Vaccine trial process

Preclinical Phase I Phase II Phase III

Participants

Goals

Animals

20-100people 100-200

peoplethousands ofpeople

Produce animmuneresponse?

Protect afterviral challenge?

Safe?Immune

response?

Best dose?Safe?Magnitude/types ofimmuneresponse?

Does it work?


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How do you know if a vaccine works?

HIV-negativeparticipantsHIV-negativeparticipants

Risk-reductioncounseling

Risk-reductioncounseling

Vaccineis 75%

effective


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Slidecourtesy

ofAVAC


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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


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Participants for HIV vaccine research

Participants shouldrepresent different:

Sexes

Races/Ethnicities

Socioeconomicbackgrounds

Potential routes oftransmission

Environmentalbackgrounds

HIV risk levels


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Risks of Participation

Like most vaccines, the HIV vaccines used in clinicaltrials 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 HIVvaccines tested to date


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Risk behavior in trials

Participants in clinical trials are continually counseledon how to reduce the risk of being exposed to HIVinfection

No evidence that participation in HIV vaccineresearch leads individuals to engage in behaviors thatincrease their HIV risk

Data from several trials completed to date shows thatrisk behaviors usually decline overall, particularlyduring the vaccination period when study visits aremore frequent


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Vaccine-induced seropositivity

HIV vaccines are designed to provoke immuneresponses this includes antibody production

Standard tests for HIV detect antibodies, not virus

Study participants who receive HIV vaccines will oftentest positive (seropositive) on these standard tests butit 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


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Key clinical trial milestones:HIV vaccine research

Results ofPhase III

Thai Trial(RV144)

HVTN 505enrollment

begins

1980 1990 2000 2010

First HIVvaccine

trial opensPhase II Stepand Phambilistudies halted

VaxGencandidate fails

in Phase IIItrials

HIV identified

?


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True or false?

Participants might get HIV from the vaccine beingtested.

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, itmeans they have HIV.

Researchers test HIV vaccines by administering the

vaccine and then exposing the participants to thevirus.

Researchers try to get participants to engage in high-risk behavior so that they get exposed to the virus.


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How people can help find an HIV vaccine:

Educate themselves and others about HIV vaccineresearch 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.


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BeTheGeneration.NIH.gov


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Vaccine efficacy trial plans, 2006

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

Enrollment Follow-up

STEP

RV

144

HVTN

503

PAVE

100

2003

Anticipated Data Availability

HVTN 503

PAVE 100

RV 144

Merck 023/HVTN 502 (STEP)

2004 2005 2006 20112007 2008 2009 2010


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Vaccine efficacy trials what really happened

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 S R

H

P

RV 144

Merck 023/HVTN 502 (STEP)

HVTN 505

20112007 2008 2009 20102003 2004 2005 2006

Documents

HIV Vaccine Clinical Trials Participation (Katharine Kripke)