A Human Question: 15th International AIDS Conference in Bangkok 6
Director: T. Jayashree
Duration: 00:59:10; Aspect Ratio: 1.333:1; Hue: 19.031; Saturation: 0.215; Lightness: 0.369; Volume: 0.120; Cuts per Minute: 18.367; Words per Minute: 116.944
Summary: Tracing the story of the global struggle to make HIV/AIDS drugs more affordable and available, A Human Question raises key questions of whether private ownership of knowledge can be at the costs of human life? Event Keywords: Press Conference on Thai Drug Policy, FTA, AIDS VACCINE, Vaccine trials.
what this paper is arguing is that, inorder to access medicine in Thailand and other countries, what we are saying is strict rules and ----------- rights should be out of the free trade agreement. And I would like to invite u after this to go out of this media centre where we have an event and show the effect of the free trade agreement on Thailand.
Man in strips : Thanks very much. We have a few minutes if people have any questions and also as (name) mentioned we are going to have a photo oppurtunity outside at 1.
End of P C on Thai drug policy
Welcome to this PC. I'm Dr Seth Berkeley, President and CEO of the International Aids Vaccine Initiative, and next to me is Dr Wayne Koff, who is the Senior Vice-President for Research at IAVI as well. Just to say a word - IAVI is a public-private partnership, the world's largest organisation focussed solely on AIDS vaccine development. And we're really delighted to be here. It's appropriate to be here in Thailand, given not only the Thai leadership that's occurred on AIDS, but also the Thai leadership that's occurred on AIDS vaccines. And yet you know, and you heard yesterday, that there are 10 million new infections that are expected in Asia by 2010.
So if you take home one message from this small press conference, it is that only a vaccine can end the epidemic, that other efforts can slow down and mitigate the consequences, and improve the quality and length of life, and those must be done, and they're absolutely critical. But only a vaccine can end the epidemic. The conference theme is Access for All, and you heard at the opening ceremony that that doesn't mean just treatment. We need to be sure to include prevention as well as research for new prevention technologies such as vaccines, microbicides and new diagnostics. However, despite my saying this, you may have noticed in the opening session that vaccines were not mentioned by any of the speakers. And I think that's an important point because there's somehow an assumption that vaccines are going to occur even if there's not a drive to do that, and I think that's wrong. I think our job is to get vaccines to be part of the comprehensive agenda of AIDS. You heard yesterday that last year there were more infections than ever with really no end in sight. So I think the challenge for the world is that we in fact need a vaccine more than ever.
So what does the world need to do? Over the short term, we have to deal with the emergency that exists today. That includes getting the prevention tools that we have today out, treating those who are infected and mitigating the consequences of the infection. Over the long term, though, we have to create these new tools to end the epidemic, and the creation of the tools is also an emergency given the nature of the epidemic, and therefore speed must be a guiding principle.
So...every two years we release a report on the state of the AIDS vaccine field. And in your press kit is this executive summary of that with all the charts. There also is, for people interested, the more detailed report that covers the entire field and everything related to it. Wayne is going to summarise some of the technical information. But we've seen many changes over the last few years; we've seen the AIDS vaccine go from very little effort and very little progress to now, a much more substantial effort with some real progress. However there are still significant challenges. The current efforts are not of adequate magnitude to guarantee that we will succeed in the shortest time possible, nor that we will have vaccines that meet the needs of developing countries. And obviously those must be our two goals. So what are some of the things that need to happen? And again they are in the blueprint : we need an enhanced science effort using the industrial model to drive forward AIDS vaccine; we need to extend the pipeline of existing candidates, and move vaccines in parallel and not sequentially. We also need to systematically solve the remaining scientific challenges which are holding us back. We still need increased resources, and these need to be targeted at applied research and product development and not just basic research. Currently, less than 1% of global health research is going through AIDS vaccines, and less than 3% of all of the money going into AIDS. Third, we need increased political commitment for speed and resources. You heard the G8 recently made a commitment in June to try to go ahead and push forward more resources and co-operation for AIDS vaccines. But this is the fifth time the G8 has spoken out on AIDS vaccines and the challenge is to turn those commitments into leadership and resources.
We also need to ensure that we have full developing country engagement - not just in testing, but in the science, in leadership, in policy work and access. We must have partners with those who are living in the most affected areas. And lastly, we need to plan for success so that we can guarantee that we can get vaccines to those who need them, and not repeat what has happened with AIDS drugs. Now what I'm going to do is turn it over to Wayne who is going to go into more details, and then I'll come back later and wrap up.
Thanks a lot, and what I want to do is - I want to walk though some of the progress that has occurred over the last couple of years. And then I want to point out three or four of the key obstacles that are in the path of the AIDS vaccine. So if we look at the advances first, we now have seen a tremendous expansion of the pipeline. At this point in time, we have a total of 30 candidates in the pipeline, which is really about a threefold increase over what we saw at the Barcelona Conference. So this has really been a significant advance. A second point is, there has been a tremendous amount of work in the developing world, and at this point tin time, we have 15 of the countries in the developing world that have tested AIDS vaccines. And we need this, because the epidemic is worst in the developing world, and this is where the efficacy trials are going to be done, and lastly, and I think the most important point is, we're beginning to now see answers on some of the initial candidates. The initial AIDS vaccine that has gone through all stages of the testing is the VAX and the GP 120 vaccine (check), and that has been run in the efficacy trials in this country and in the United States, and we now have another candidate - a combination approach, which is the ____vaccine, as a prime, and the ____vaccine as a booster. And this candidate is in the middle of the efficacy trials, and we expect to see the data sometime in 07-08. And lastly, and perhaps more excitingly in the effort now, is there is a candidate that is based on the ____virus vector. This is the ____vaccine that we expect to see it entering into efficacy trials by the end of the year. So in the past two years, we have seen a real advance in the numbers of the candidates in the pipeline, in the progress of those candidates in the pipeline, and in the role of the developing world as partners in the AIDS vaccine effort.
I want to turn now to a few of the obstacles in the path of the vaccine, and the initial obstacle is that, even though we have widened the pipeline, it seems as if almost all of the candidates in the pipeline in the present time are working on a single approach. And that is to see if the T-cell immunity is effective in the suppressing of HIV. And this is an important approach, and yet there are a number of other ideas out there that have to be examined. One example is, will effective antibodies against HIV work? And another is, do we need a ____immunity to attack the virus at the site of entry into the host. We also have a number of other research challenges : as an example, we don't know at the present time which of the proteins of the virus are needed for an effective AIDS vaccine. And one the tools that we are looking at is the ___vaccine, and we have known for over a decade, that in the monthly models, ___vaccine like our paediatric vaccines is extremely effective. In fact, it's the best vaccine in the monthly models. However, we don't know why that vaccine is working. We don't know if it is neutralising antibody, or cell ____immunity, or _____immunity. So these are some of the research challenges that we have to address. And finally, even though there is a lot of the capacity now for the initial trials in the developing world, that is the safety trials, there is a lack of the capacity for the efficacy trials for the AIDS vaccine. And so we need to really expand our effort there. As ___pointed out, each year only 650 million is spent on the AIDS vaccine effort. And this is 1% of the dollars that are used on the health product of the ____. This is not enough. We need to increase the resources, and the blueprint is calling for the doubling of the resources. And the use of these increased resources will be in 3 or 4 key areas. One is the prioritisation of the pipeline. We have 30 of the candidates in the pipeline. We have to be able to identify which is the best of the candidates. And so we need a process of standard assays and labs that are effective on these assays. And secondly, we need to have the production capability to ensure that the best vaccines are made to the international standard. And finally, we need to test the concepts in the efficacy trials as soon as possible. If the ___vaccine, as an example, begins testing by the end of the year, we'll have data again sometime in the 07-08 timeframe. And one of three things will occur - if that vaccine is extremely effective, we'll be hearing 4 years arguing about speed and access and licensing. If that vaccine is partially effective, there needs to be a process of improvement on the vaccine. And if that vaccine is not effective, then we have to focus a lot more attention on the scientific challenges. And so, as a final point, I come back to the point of the scientific challenges. To improve the next round of the candidates, we have to begin to answer the kinds of questions that we haven't been able to answer in this field for a long time. Thank you.
Thank you very much, Wayne. Now joining us, a little bit late, but always perfect to have her with us, is Dr Helene Gayle, who is at the Bill and Melinda Gates Foundation , but also is co-chair of the HIV prevention working group whose report was released earlier this week, and President-elect of the International AIDS Society, and she's going to comment now.
Thanks, Seth and Wayne, and it's really my pleasure to be here on this panel with IAVI. Seth didn't mention specifically, but the Bill and Melinda Gates Foundation is one of the major donors to the IAVI, and so we're really pleased to be part of this PC to talk about this issue of the development of a safe and effective HIV vaccine. As Dr Berkeley mentioned, I chair...co-chair the Global AIDS and HIV Prevention Working Group, and clearly we feel that while access to antiretroviral is a key issue and a lot of focus is going continue to be put on that, in the long run preventing people from getting HIV infection to begin with, has to continue to be the world's priority. Even to keep pace with the very ambitious goals that we set out for ourselves for getting people on antiretroviral therapy, for example the 3 by 5 initiative, well if you think about the fact that we have 5 million infections every year, we're not going to be able to keep pace with the goals that we've set for ourselves for treatment if we don't continue to keep our focus on preventing the further spread of HIV. And so just to keep pace with our current goals,, and imagine if we continue to let HIV infection increase around the world, you all know what the different estimates are. But I think, tellingly the UNAIDS Report says that is the year where greatest number of new HIV infections occurred worldwide. So clearly we must have a comprehensive approach. It has to include scale up of antiretrovirals, but it also has to continue and in fact increase the focus on prevention. But we know that while we know that there's a lot that can be done today to reduce the spread of new HIV infections and the last three reports that our working group has put out has talked about what we already know, what the strategies are today that could make a difference for the spread of HIV. We also know that without greater expansion of the options for prevention, we're not going to have the impact that we need in the long run, and that of those different options, the new prevention tools, clearly at the head of that has to be a focus on expanding efforts for finding a safe and effective HIV vaccine. For any infectious disease, particularly viral infectious diseases, vaccines have really been the mainstay of really halting the spread globally. So we're firmly behind the goals of IAVI to develop a safe and effective HIV vaccine. And I would also just parenthetically say that we're also very involved in expanding of new prevention tools. Broadly, on Wednesday in the same room, we're going to have a session which looks at other prevention options like microbicides, diaphragms, oral ARV's, etc. but that's not the topic of my talk today. So let me go back to HIV vaccines.
One of the things that we're very happy about, and pleased in our partnership with IAVI, is developing a new approach to the development of an HIV vaccine. This is the HIV vaccine Enterprise. A few people might have heard about it. It was recently endorsed by the G8 at their most recent summit at Sea Island, Georgia. It's a collaborative effort with partners around the world working on the development of an HIV vaccine to better co-ordinate the efforts globally in a similar fashion to the Genome Project, where no one organisation owns it, but it was an opportunity to better network all the organisations working on this very very important global effort to do it in a more co-ordinated way, to scale up the effort, to do it in a way that learns from the experiences of other researchers, and really hopefully accelerate our efforts to find a new vaccine.
Today many of the efforts that we have are more often to be discrete scientific studies that don't necessarily share information in a way that would be useful to other researchers in the field. And what we've found is that there is a lot of redundancy, oftentimes duplication of approaches, and if we're all going down the same pathway, and that pathway ends up not being the right pathway, we've spent a lot of time, resources and energy that could have been saved had we been talking to ourselves more, working in a more collaborative way, and hopefully doing it in a way that is as effective as possible with the resources available, so that it could garner even greater resources for its efforts. So I would just stop there and say that we're really pleased to be working with IAVI, with other partners, to really foster this approach of the HIV Vaccine Enterprise, and hope that it really will be a step in moving forward a global...even better and more co-ordinated global effort to find as efficiently and as effectively, a safe HIV vaccine that will have the impact of reducing new infections globally, and will be an important edge up to the work that's been done to provide treatment to people already infected with HIV
Thank you very much, Helene. I just will say a word about what IAVI is to some of the new people here, and then we'll open it up for questions. IAVI is a public-private partnership and not for profit. Our vision is a World without AIDS, our mission is to ensure the development of a safe and effective preventive HIV vaccine for use throughout the world. Four major strategies - one is an aggressive R&D programme, 75% of our industry staff comes out of industry, we've taken 5 vaccines into the clinic over the last 5 years, we're currently doing clinical trials in 8 countries, and have set up laboratories to do validate assays to make sure that we priorities candidates across all of these different countries, and we're also working on trying to (inaudible word) applied research. We have an active program to try to keep vaccines on the agenda, through advocacy, promoting supportive public policies, to try to change the environment out there for our vaccines, and to work with our developing country partners. So with that let me open this up for questions.
Audience member : We've all been hearing for a couple of years now about the great need for standardised lab assays to look at immune parameters of success and failure for vaccines. Can you tell us why...it's clear from your talk today why we don't yet have a vaccine that works...but why there aren't a set of agree-upon immunologic assays? How much of it is due to scientific uncertainty? How much of it is due to intellectual proprietary issues? How much of it is due to debate and dissent from company to company? If these simple building blocks would catapult your results forward, why don't we have them?
Koff : I think the answer to that is really twofold : one is that if you talk to all of the major players in this field, I think there is a general agreement on what are the key assays, and in fact IAVI has set up a core lab that has validated its standardised assays, as has the HBTN of the NIH, and a number of the other partners. I think what occurs is that each group until recently has only had the resources to work on their own vaccines. As we've expanded now, we've begun to examine other vaccines outside of the IAVI sponsored vaccines, and we aim to increase this activity. Because at the end of the day you want to know the ranking of the candidates, of the resources used on the better candidates.
Helene : And just to add, that's the very reason the HIV Vaccine Enterprise is being created, so that that kind of information sharing can take place, so that laboratory standardisation is one of the key issues the Enterprise will be focussing on, are vaccines, discovery vaccines, development and manufacturing, laboratory standardisation, clinical trials, and some of the overarching issues like IP, how do you share information and at the same time make sure that you're not, giving a disincentive for people to work in this area. So those are the kind of things that, working on a consortium approach...and IAVI has already taken a leadership role in looking at some of these issues, and we want to expand that even further.
Berkley : One other point before we move to the next question, and that is that we don't understand fully the correlate of protection, so there's a separate issue, which is one, validating the assay out there, and you've heard the previous two speakers talk about the importance of that, and the need to do that, but there's a second critical issue: they don't necessarily correlate within, let's say a monkey model, with protection. So we know we can get protection, but we don't necessarily show that those particular assays correlate. So we have to use something, and we want to standardise those, but this is one of the reasons one has to go back and begin to ask questions like we suggest in the blueprint: why does a live attenuated virus work? What are the correlates that make that work? And then we'd at least have something that we can target measurement against, which might predict protection in that model. So it's both using the existing assays better, but also creating new assays that correlate better with the animal models.
Audience Question : You spoke of...we don't fully understand the correlates of protection. There's a Quest for the Holy Grail here, isn't it? If there's someone out there, hopefully, who's got natural protection against HIV, who's got the antibodies, what kind of work is going on out there to identify that person among the 6 billion people who may have the genetic clues that could be used through reverse engineering to make this wonderful vaccine?
Koff : That's an extremely important point. As it turns out, we have now, in our aegis, about a handful of the monotonal antibodies, and these are antibodies that have come out of individuals that are HIV infected and who have the ability of the neutralising activity of these antibodies against a spectrum of the isolates, and so what we've got in fact is a lock, and we don't have the key. And so to try and find the key now, we have set up something called the neutralising antibody consortium, which has brought in a number of the best of the laboratories in this field to begin to look at the crystals of the antibodies, the crystals of the proteins on the surface of HIV, and as one of the artists would, to begin to sculpt out of the different approaches the key. At this point of time we have made incremental progress. We've had proteins that we have made that are neutralising a range of the isolates, but are not as effective as the _______antibodies. We need to keep carving out on that key till we actually open up a lock.
Berkley : On the cell mediated side, the other arm of the immune system, we now have many individuals who are highly exposed and infected, and who have cell mediate immunity, and so what we're testing with those vaccines is - would that immunity prospectively protect people from progression to disease or even from becoming infected? And those results are now in the process of coming through. And as you heard, there is now one product that is in phase 3 now, there are a couple more that are potentially moving forward. So we will have an answer to that as well.
Audience Question : Dr Koff indicated that there were 30 candidates, but they were all related to a similar approach - on T-cell immunity - for the 650 million dollars that you're calling for, how would you break down your spending between basic science and clinical trials? Clinical trials would be more expensive, but these would be all rather similar entities. A quick follow up on the G8, you were somewhat dismissive of having five G8 declarations in favour of vaccines. Do you think this one's going to pay up?
Berkley : Let me start with the beginning. What I said was that there have been five, and what we need to do is make sure that it's followed with resources and leadership. So I don't ever want to be dismissive of the G8. I'm delighted they're doing that. I'm delighted of the leadership work that's going on by the Gates Foundation and others. The challenge is going to be, can we turn that now into a real commitment? In terms of the dollar related issues, I would argue that what we need to do is redouble our efforts at making better products, and at solving these scientific problems now in an industry-like model, not to dramatically increase large numbers of trials. We will need to take a number of products forward, but we need to make sure those are best of class, and that's one of the reasons that we have to create this prioritisation process. What we don't want is ten of the same vaccines released, or at least very similar vaccines, but rather the best of that class, the best of another class...
Koff : I just wanted to add on to that. At this point in time we have at least 11 or so of DNA vaccines that are in vaccine trials now. And among those, it is unlikely there are a lot of significant differences between them. So I'm just pointing out on this prioritisation process, what we really want to do is wean down to the one or two that are the most of the interesting of the candidates. At the same time though, it's really important, as we don't understand yet what the target is to be able to move the best of the candidate into the efficacy trials as fast as we can. And that is expensive, it's expensive in terms of the building of the laboratories and the infrastructure, and the (inaudible word) and of the running of the vaccine trial itself.
Helene : May I just add, the point about the G8 is that, while there have been past declarations, this is the first declaration that I know, that...immediately following that, there was a promise of money. The US committed 15 million dollars to a new vaccine development centre. They also called for a follow-up meeting in this calendar year to talk more concretely about next steps. So this is the first one that I know of, of all the ones that you mentioned, that actually calls for...that one put the money on the table immediately, and calls for some accountability on the issue. So I'm hopeful that this can actually move forward in different ways than past declarations have.
Audience Question : You talked a lot of time about the live virus, HIV virus, so... other groups preparing clinical trials with those kinds of vaccines, ____ they could have severe side effects, cancer in the long run. Do you think that those live vaccines could be an alternative to work against the redundancy you talked about?
Koff : I think at this point it's too early in the work on the AIDS vaccine to consider a live attenuated as a viable HIV vaccine candidates. I think the issues of the potential of the reversion of the vaccine to a ___type virus. Basically, it's taken that off the table at this point. However it's critical to try and identify why the concept of a live vaccine, in the SIV model, in the monkey model, is working as well as it is...(BREAK)
Audience Question : I wonder if you can talk a bit more about the timeline. You talked about the...the ___vaccine seems to be a year behind the ____ AIDS vaccine going into phase 3. But you said that both could have results in 2007-08. Is that realistic? Can you explain why the ____ one could be so much quicker? And secondly, could you comment a bit about the after-effects of this? What sort of response would be worthwhile having, you think? (BREAK)
Berkeley : ...it is taking longer than the ___ product. The ____ product, it is planned, it hasn't yet been formally announced, but the plan is to do a phase 2 B trial, that is a proof of concept trial, where the goal is instead of trying to get a value that is license-able, what you want to do is prove that in fact the vaccine works. So you don't need to get the same level of confidence. That trial would probably be a few thousand people, rather than tens of thousands possible, and therefore the trial can be enrolled quicker. My prediction would be that more and more people would try to do those kinds of trials first to get quick answers and then, if they are successful, to roll them into efficacy trials and at that point you can expand your efficacy trial to multiple different parts of the world looking at different populations as well. In terms of the issue on effectiveness, obviously the more effective and simpler to use it is the better. But mathematical modelling has shown that a vaccine of effectiveness even as low as 30% could have a dramatic effect on the epidemic if it was used in high-risk populations.
Audience Question : I have two questions. First, you said to know the issue of using animal models in Europe, especially a kind of species of the primates; animal advocates are against it. Are you changing it to the baboon model, because it has not been used as an ___, and now as you move to Africa, where you have as in Kenya baboons... I don't know if you're going to move to baboon models. Also, secondly, I wanted to know in terms of HIV subtypes, the vaccine constructs are based on subtype A, B and C. you can't construct one based on all subtypes...(BREAK)..
Lastly, I just wanted to know, on the issue of volunteers, Dr ___ didn't talk about it in developing countries as a challenge. How are you going to go about it when you want to accelerate your clinical trials?
Koff : In terms of the monkey models, the emphasis of the work has been in two of the species of the monkeys. The emphasis of our ___ studies is done in the Indian Rhesus monkey as a priority model, and the immunogenicity studies are done in a range of other species of monkeys, and this includes a number of different kinds of the species. So we're not linking it to one or the other species of monkey. I think in terms of the issue of subtypes, we don't know at this point in time if a single vaccine is going to be effective against a range of the variable isolates of HIV, or if in fact we're going to need a cocktail of the vaccines. There is a lot of data in the animal model systems and some of the data in the early stage of the phase 1 trials to suggest that there is an extensive amount of ____ activity that is seen with a number of these T-cell base vaccines, such as the ___ vaccine, so until we do the efficacy trial, and see the level of the efficacy in the people, we aren't going to be able to answer that. In terms of the third issue of the volunteers, it is always a challenge all over the world to increase the number and speed of the enrolment of the volunteers. There is a lot of discussion in a lot of meetings, and at this meeting. And at the increase in the number of women in the vaccine trials - this has been a traditional problem. And it really speaks to the model of the partnership that we have to engage the communities early, we have to be as active as we can in the education and the counselling efforts, and we have to just keep going after it. I think our record as a field is getting a lot better now in terms of the speed and enrolment of the volunteers.
Berkley : If I can just emphasise on other point on that, in terms of the species of primates, it's not only the species of primates, and Wayne has answered that, but also what the challenge studies are, and what we know is, there are different potential challenges, and depending on vaccine, you get protection with one type of challenge and not with the other. The reason that's important - until we show protection in humans we're still guessing on which of those challenge models are the right model. So they help us to prioritise, but we can't be definitive about them until we actually have those results in humans.
Audience Q : I'd like to ask you about the Global Vaccine Enterprise, the analogy with the Human Genome Project is of course very apt. But also it strikes me that that's a far more simplistic model to follow, because as far as I understand it, that was about logistics and doing things on an enormous scale, but the actual strategies involved were much more straightforward in it. There was more consensus over what we have to do - the secrets of the genome. It seems to me, though, that with vaccine research, there are so many different strategies, so many different organisations. How will you ensure that this Global Vaccine Enterprise will actually be effective and will really pull its weight. And how do you stop the individual players just carrying on with business as usual?
Helene : Yeah, I think first of all this is something we're still in the process of, creating, if you will, but I think you're right that in some ways the task of the genome was perhaps simpler although when we talked to people who were involved in that effort, they say, you know, it may look from the outside that we knew what we were doing and that we had a clear sense of how this was going to work, but we didn't when we started. So I think anytime we talk about putting together a global scientific community it's not straightforward. But I think one of the things that we have worked on over the last few months is to get a blueprint in place, similar to what we were talking about today looking at what are the highest priority activities, so that at least we have something that everybody is working off off the same page. That we have a common set of issues that we see as priority issues, and the kind of challenges that Wayne and Seth have already outlined. But it's really how do you do it in a different way, that really does pull people together. I think that, given that we're now 20 years into HIV vaccine research, there's a great sense from the researchers themselves that if we keep doing things the way we're doing them, we could be, 20 years from now, saying the same thing. So I think a lot of the impetus is from people themselves who have been working on this for a long while and realised that if we have a much more co-ordinated global effort where we're talking to each other, sharing information, making sure that we're looking in a more systematic way at the different approaches, so we're not all moving in one direction with a single approach and really looking at it in a much more ____fashion that we will be much more further ahead. How much further ahead, how much sooner we'll get there, it's hard to predict at this point, but I think everybody thinks that that if we don't do it, having a kind of fractionated approach to it will only slow our efforts down. It will take more resources, and in answer to your question, I think that's one the things that will make a difference...
Audience Question : I'd like to know first, why after 20 years of AIDS there is still no vaccine, second, when do you think the first vaccine could be ready?
Berkley : Let me start by building on what Helene said, which is : first of all, there hasn't been much of a vaccine effort. So yes, it's very easy to say, it's been 20 years, but as a few years ago, we were able to stand up here and say, no vaccine had been tested to see if it worked on humans. And we've now had one candidate fully tested to see if it works on humans. That is a global disgrace. So when you really begin to ask the question, is it because we've had a maximum effort over this time and we've failed, not the case at all. There has not been a serious effort, there has not been a constituency, there hasn't been a driving force, there haven't been adequate resources, and so getting a serious effort underway is the first priority. In terms of the question of when we will have a vaccine, obviously if there's not going to be a serious effort we're never going to get there. There is now beginning to be a more serious effort, and we've laid out in the blueprint the evidence suggesting that we're moving forward more rapidly. If we're lucky, some of those candidates will provide protection in humans. And then we've got critical clues, but we can't take that for granted given the timeline. And that's why we've got to have other approaches moving forward simultaneously. BREAK
Audience Member : Can you comment on the doubts that many scientists have expressed about the _____ trial in Thailand?
Berkley : The ____ trial in Thailand? The ___ trial that's been completed? Is that the one?....(Audience : the ___ trial that's still recruiting volunteers, that one.) Well I would suggest that since you're here in Thailand that you talk to some of the groups that are sponsoring them, that is the Thai Ministry of Public Health and then, the US Government AIDS initiative. Those are the people sponsoring those trials. Let me just say that of course we have scientifically valid trials moving forward, and this is a trial that has gone through a lot of pre-review, and so we're supportive of seeing that trial through. Some of the controversy related to the fact that the AIDS vac was in that trial, and there had been recent data that showed it not to be efficacious, and so some people were questioning whether that...BREAK
Audience member : Just a question about the challenge of conducting large-scale phase 3 trials. Ironically we are here in Thailand where _____ probably have the most experience of that of any place in the world. But they've also pretty much expended the pool of candidates who might be available for such large-scale trials. I see there are trials planned for India as well. Where do you see the next ground occurring?
Koff : I think that at this point in time, the ideas on the ___ vaccine trial are likely to be in the United States and in some of the Latin American countries, but again that's only a proof of concept study. As we go ahead into some of the larger efficacy trials, it's really going to be up to a number of stakeholders to really get out there and build the infrastructure and the capacity, which isn't there at the moment. BREAK
...and it's the human resource infrastructure, it's the epidemiological, the background, the data, the laboratory, it's the community, it's the whole package, and so there's a building effort that's really needs to be done.
Helene : I hate to sound like a broken record, but that's partly why the HIV Vaccine Enterprise should be helpful, because with 5 million new infections every year, the issue is not, do we have enough HIV occurring? Unfortunately we do, but it's matching the right sites with trials and being able to kind of systematically look at where should we be able to build up sites, looking at where the emerging epidemics are, so that we know that those are the places where there are going to be high rates of new infection and would be good for vaccine trials, and actually look at that very systematically to make sure that we're matching our trial resources with where infection is. So I think it is doable, but as you said, there are a large number...potentially the need for a large number of people, and I think it's important to keep in mind that it's not only for HIV vaccine trials, but this is going to be critical for microbicide trials, and any other prevention trials that have to be done, making sure that we do a really good job of building the infrastructure, so we have the triocytes, can do this as quickly as possible so that we can stop new infections and save lives.
(BREAK)...and volunteer for trials, and what we've seen in all of our work, people always say, well how do you get people to volunteer, isn't it difficult, isn't it hard. We've seen a dramatic outpouring, usually for altruistic reasons and in our experience, we're now doing trials in 8 countries, we've been able to get volunteers. The process has sped up over time and it's dramatic to see what communities can do in terms of doing this. So in our sites in Kenya, in our sites in Uganda and other sites, we've seen dramatic outpouring of interest in this. So it is possible, and as Helene said the challenge is the infrastructure, but I believe that we'll be able to get adequate volunteers for this. Thank you...