HIV Vaccine Research Update: The PAVE 100 Trial

PAVE 100 is a proposed efficacy trial of an HIV vaccine developed by the National Institute’s of Health (NIH) Vaccine Research Center (VRC). The vaccine candidate to be tested in PAVE 100 is a combination of an HIV DNA prime immunization and a recombinant adenovirus type 5 (rAD5) vectored boost. PAVE 100 was originally scheduled to begin in September of 2007, enrolling 8,500 participants internationally. NIH immediately postponed the trial when the Merck ® STEP study, which tested a different Ad5-vectored vaccine concept, was halted due to futility and possible increased risk of infection.

Since the discontinuation of STEP, the scientific community has been debating the fate of PAVE. Months of consultation and STEP data analysis led the PAVE protocol team, led by Dr. Scott Hammer, to propose a new PAVE 100 study to begin as early as January 2009. Dr. Hammer unveiled the modified study design at the HIV Vaccine Trial’s Network’s (HVTN) annual conference in Washington, DC from May 21-23. The HVTN, a PAVE 100 partner, is an international organization of scientists and educators that facilitates the production and testing of HIV vaccines throughout the World.

While presenting the new trial design and rationale for moving forward, Hammer referenced differences between the PAVE 100 and Merck candidates, highlighting the new design’s increased safety measures. The study now intends to only enroll 3,000 participants who are uncircumcised, ad 5 negative men who have sex with men in the United States because ad 5 seropositive men were at increased risk for acquisition in STEP. The original trial was designed for direct licensure of an HIV vaccine, but the new trial is only a “test of concept”. The trial will study safety, tolerability and immune response and should answer important scientific and immunologic questions, not the overall efficacy of a vaccine product ready for licensure.

Dr. Hammer explained that the study will inform the field of other DNA prime/viral vector boost approaches, and improve future “test of concept” clinical trials. While the results will not be generalized due to the small study population, it could show efficacy. The PAVE 100 protocol team thinks any sign of vaccine efficacy would be helpful in developing future vaccines for all populations.

On Friday, May 30, 2008, the AIDS Vaccine Research Subcommittee (AVRS), a research advisory committee for the National Institute of Allergy and Infectious Diseases (NIAID), met to discuss the proposed PAVE 100 study. Dr. Hammer presented the study’s proposed protocol design to the committee, who also heard presentations from community representatives. The status of PAVE 100 was not decided at this meeting. Now informed, the AVRS is expected to provide NIAID with a technical assessment of the proposed study and recommendations for moving forward. Dr. Anthony Fauci, Director of NIAID, will use this assessment and other pertinent input to decide if the NIAID will conduct the PAVE 100 trial.

Enid Moore, representing the HVTN, began the community panel. Moore coordinated several calls and meetings among the Community Advisory Boards (CAB) of local trial sites to form community recommendations for the PAVE 100 trial. She explained that while CAB members support the PAVE 100 trial, there is anxiety about the risk. Moore urged the protocol committee to remain cautious given the many questions still unanswered from STEP. Moore also reminded the group that if the trial fails, HIV vaccine research fields risk losing the community’s trust. CAB members suggested that if the trial goes forward, the protocol team must increase CAB representatives on the protocol team, increase community education, provide clear messages to community, educators and recruiters, and develop a proactive media strategy.

The National HIV Vaccine Research Education Initiative (NHVREI), represented by project coordinator Stacey Little, urged the committee to further educate communities on the benefits and advantages of conducting the study before moving forward with PAVE. AIDS Action is a National Partner of NHVREI and was represented by this group.

Mitchell Warren, Executive Director of the AIDS Advocacy Coalition (AVAC), informed the committee that NIAID must prepare to move forward regardless of PAVE’s future. AVAC has coordinated civil society calls in the broader AIDS service community, but claims more efforts are needed. AVAC believes the protocol team must clarify for communities that must support and participate in the clinical trials, what questions the PAVE study is trying to answer. Mitchell concluded that the mechanisms to make the trial a success are not yet in place.

After a public comment period the committee met privately to make an assessment. Prior to deliberation, Dr. Fauci assured the committee that there was no predetermined decision and he would seriously consider the views expressed. The committee’s recommendations to Dr. Fauci have not been made public.

To view the AVRS meeting web cast, please click here.

NIAID is creating a website for PAVE to provide information on further decisions about the study. The page is not yet updated with information, but can soon be found here.

For further information on the PAVE 100 trial, please visit AVAC’s website.

The AIDS Action Weekly Update

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