Yamada
Over the past  2 years:
- 2  millions have initiated ART
- 5 millions have been newly infected
- Advances : discovery of circumcision as a preventive measure in men
- Setbacks represented by vaccine and microbicide trials failures
Lessons learned
- Vaccine  is a difficult endeavor (1/10 vaccines will undergo development)
- Technical aspects (standard of care for controls and non adherence in intervention groups)
- Animal models don’t preclude what happens in humans
- Definition of correlates of protection  unclear
More collaboration and cooperation is needed to synergize efforts and reduce duplication

Alan Bernstein
Integrated plan for prevention with vaccines is needed
- Short –term:  expand what works (i.e.,  ART)
- Medium term :  continue research  with circumcision and microbicides
- Long-term:  expand vaccine research to understand human immune response through
? Research of post genomics
? Research in elite or long term non progressors
? Retaining  and attracting new generation of researchers
? Exploiting better NHP models
? Shifting  focus from licensure mindset  to research mindset
? Better connecting product development and fundamental research
Consortia approaches (CHAVI, BMGF, EuroVac etc).
- Develop new markers to understand and monitor immune response ( other than Elispot)
- Viral load and clinical  protection are imperfect proxies of vaccine efficacy
Global Enterprise :
- Global Strategic plan
- Neutral convener
- Honest broker
- Catalyst
Susan Buchbinder
STEP trial with Ad5 vaccine construct showed an increased risk of HIV acquisition in vaccinees  compared to control.   The increased risk was 4 fold among vaccinees with a high titers of  pre-existing immunity to Ad5 and  uncircumcised participants. This increased risk is stable over time ( at least 78 weeks)
The next steps in the study include:
- Roll-over to a follow-up study (since retention has been excellent> 95%)
- Awaiting  data on HSV2 status, HLA typing, sexual networks, longitudinal analysis on risk overtime and lab investigations
- Open up  opportunities for collaborators with other group for specimen sharing
Lessons learned
- Utility of POC (proof of Concept Trial)
- New questions not addressed  by NHP models (transmission across mucosal barriers)
- Data  and specimens to address failure to protect ( functional assay to measure cell-mediated immunity)
- Community lessons
o Transparency is vital
o Prepare community for the unexpected
o Each prevention trial impacts on other prevention trials

Seth Berkeley
Successful  vaccine will likely require induction of broadly  NAb. Live attenuated SIV controls homologous  challenges in NHPs  and in human (elite controllers)
Successful vaccine will require:
- Breakthrough in Nab
- Development of more potent vectors ( ie replicating viral vectors)
- Multiclade HIV antigenic insert
Development of international neutralizing antibody consortia and replicating vector portfolio
IAVI: VSV, VEEV, CDV, NDV. Reo
Non-IAVI:  Measles, attenuated VSV,  Adenovirus 5/7,  vaccinia virus.

Rosenberg
95 trials have been completed or stopped
- Surfactants
- Polyanions
2 currently ongoing trials of polyanions (Buffer gel /PRO 2000)
Next generation: ARV-based HIV specific (once a day/once a month) in different formulas(gel applicator, rings, tablets/capsules)
Needs to be part of a comprehensive package (microbicides, vaccines, PrEP)
Tenofovir
- 3 trials completed , 1 in analysis,  3 ongoing and 1 planned for Q1n2009
Dapivirine (TMC120)
- Potent NNRTI:  phase I/II competed and ongoing,  phase III planned for 2010
- Completed trials show good sfety profile
UC-781
- 2 ongoing phase I studies (vaginal and male tolerance)
- 3 trials in analysis
- Combination UC-781/tenofovir  safety planned  for 2010
PC-815
- Ongoing preclinical studies in NHPs
- Phase I planned
Maraviroc (CCR5 blocker)
- Preclinical assessment ongoing
Lessons learned
- Prioritization
- Safety (will continue to look for harm)
- Adherence ( long lasting formulations work best)
- Incidence (epi studies)
- Futility (early stop if not showing efficacy)
- Pregnancy (counseling and birth  control)
- Regulatory
- Locations (make sure that enrollment is not occurring for multiple prevention  studies)

This session was moderated by Professor Elanor Preston

The presentations in this session were short position papers summarizing the current state of knowledge and current challenges in each field.  

Virtually all presenters echoed the theme of the conference - Universal Action Now, but stressed that this would not be achieved without the combined action of funders, both the private and public sectors, as well as the communities most affected by AIDS and researchers from both the medical and social sciences. The catchword of the session was Partnerships and the emphasis was on the pooling of energies, resources and also attracting the 'best brains' to work on the many problems spawned by the epidemic. Both  prevention and treatment require continued vigilance and attention. The issue of trust between researchers,funders and communities was also highlighted and explored.

The first speaker, Tachi Yamada   spoke of the advances made, for instance, in understanding the positive role of circumcision in prevention, but emphasized that in the microbicide field the results of trials were often apparently contradictory  and complex to interpret. What seemed like failures might actually prove to be enlightening in the longer term as understanding progressed. The message, echoed by later speakers, was that 'success' was nearly always built on the back of 'failures' which served ,in fact, to deepen understanding. He went on to stress the need for careful preparation and planning for trials and the realization that the use of animal models may not predict accurately what will happen in humans -'Vaccine science is more and art than  a science'. In posing the question of 'Where to from here', he   called for bright new ideas, possibly from outsiders to the medical field who would not be bound by 'accepted wisdom '  ,but would come at the problem from a radically new perspective. He pointed to the recent call by the Gates Foundation for bids for funding for work on new and very novel ideas. He also stressed the need to keep the lines of communication open between researchers and funders in an effort not to duplicate work.    

He then called on funders to put up the money for 'new ideas' – this is not the time to step away from committing really 'big' funds to AIDS research, and not to be put off by what look like initial failures. This point was echoed by a number of other speakers. Finally he stated categorically that he believed that we will eventually live in a world without AIDS.  But this will require Partnerships and particularly those which bring the profit/commercial sectors on board.

Alan Bernstein thn took up the major themes of the discussion by reiterating the need not to be afraid of failure in microbicide research “science does nor progress in a straight line”,he said. He referred to the plateauing of HIV/AIDS infections shown in the latest estimates and argued that nonetheless we still need a preventative vaccine to eradicate the disease. He called for more and more research and the necessity of attracting the best minds to the problem and bringing young people into research from all over the globe. Like the previous speaker, he called on funders to respond to the challenge and 'make things happen'. He also pointed out that people between the ages of 35 and 45 receive the most Nobel prizes for research, reiterating the call for young researchers to become involved in AIDS research, and for funders to support them.

The next speaker, Susan Buchbinder, who spoke in some detail about the lessons learned from STEP microbicide trails,   also suggested that it is not so much the results of research as what is done with them, and the new questions and eventually the research that is spawned, that is important. She spoke about adequate preparation before entering the field, but also introduced the point of the critical importance of the point oof view of the community being researched, and their response and needs. She called on the scientific community to be transparent in all its dealings with their research participant communities. 'Be prepared for the unexpected ' was her watchword, and alsso being  willing to interact and communicate with research communities. See them as partners in the research enterprise and remember that each microbicide study impacts on future studies . She ended by stressing that the one thing microbicide trails had shown was that the vaccines did not work as expected.

Seth Berkley, speaking about where IAVI is and where it is going, listed the IAVI sites around the world, calling again for partnerships, sharing of information and experiences, and of  the value of   'wild innovations' and the need to 'push the envelope' with new models. He suggested looking at other diseases such as cancer for inspiration and ideas and involving a number of different laboratories working in collaboration and partnership. Here spoke of 'clinical networks'. He was followed by Lut Van Damme who reviewed anti-viral – based microbicides and IMP, emphasizing many of the same points.

Zelda Rosenberg then spoke further about microbicide community mobilization and trial participation. She was enthusiastic about  future prospects, especially  for women of the use of highly potent ARVs which will provide them with more options to protect themselves. She called for advocates and funders to take heed of these opportunities. The possibilities, and indeed, the opportunities of involving local people as research assistants who would later act as advocates for the research and possibly, at a later date, the products.

The theme of trust between researchers and communities was mentioned by a number of speakers, and was implicit in the last two presentations by Manju Chatani and Pedro Goicochea,both of whom spoke with feeling about the complexities of managing relationships with communities, particularly where trials have to be aborted, or when the results are comlex or even negative. Sometimes psychological support may also be needed by participants, and some researchers feel that it there is an obligation to assist communities where possible with non research benefits such as the building of schools and other community facilities. The former ended by saying that all  the hurdles have to be surmounted as 'discouragement is not an option'.

Assisting participants to understand the full implications of research results was also mentioned as a responsibility of researchers and was an important part of the trust which must underpin good community relations. Both speakers were impressive in their sensitivity to communities  and their needs,but went beyond this to again stress the point that research is a partnership that all sides must honour and be willing expend effort in achieving.

The session was thought provoking and well worth following up on the conference website.