Katherine Stapp
NEW YORK, Nov 30 2006 (IPS) – Smallpox, polio and a host of other contagious, often fatal diseases have been stopped in their tracks by simple vaccines. More than two decades into the quest to untangle the secrets of the notoriously changeable HIV virus, is there still reason for hope?
IPS spoke with Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition, and Anjali Nayyar, vice president for country and regional programmes at the International AIDS Vaccine Initiative (IAVI), who helped launch the first AIDS vaccine trial in India, about the challenges research scientists around the world are currently facing.
IPS: The head of IAVI, Seth Berkley, said recently that even a partially effective AIDS vaccine given to only 30 percent of the population could halve the number of new HIV infections in the developing world . Does this reflect a scaling back of expectations, or simply the scientific reality that no single vaccine will be effective for everyone?
MITCHELL WARREN: One of the great challenges in AIDS vaccine research, and for any vaccine, is the mystique that vaccines end epidemics. And they do the only thing that ends a viral epidemic is a vaccine. I think in many respects it s not so much that we ve scaled back expectations or even that the scientific reality has changed, I think it s really in the nature of the scientific progress itself. So we re going to be looking at an iterative response where the first vaccine, the first microbicide, the first female condom is not necessarily going to be the last we hear within that category. And I think that s a good thing.
ANJALI NAYYAR: The first generation of vaccines may provide partial protection; however, they still have the potential to make a significant impact in blunting the AIDS pandemic. Our analysis reveals that even a modestly effective vaccine could slash the number of new infections by a third over a decade, saving millions of lives. A vaccine with 70 percent efficacy would have a more dramatic effect. Even if provided to only 40 percent of the population, we estimate it could avert 28 million new infections between 2015 and 2030.
IPS: If and when a vaccine does hit the market, there clearly needs to be mechanisms to ensure immediate access to those who need it. What kind of pledges have you received from governments, donors and the drug industry in this regard?
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WARREN: The AIDS vaccine field is filled with good intentions, I daresay even promises of affordable products. But what does that really mean? And will those promises stand the test of time? And the honest answer is we don t know. That s not to be cynical, it is to say that we don t know what the full manufacturing process might cost.
At the same time, we are seeing more vaccines licensed in the last year or so, and looking forward to the next year, than have been licensed in decades. We have a vaccine against cervical cancer, we have a rotavirus vaccine. The challenge is how quickly will we as a global community ensure access to those vaccines in the communities that need them the most, often in the developing world. That would be an incredible indication to Merck and many other companies that if they build it, we as a global health community will come.
NAYYAR: Access to vaccines for the poor is one of the cornerstones of our programme. The companies we work with agree to provide eventual vaccines to the public sector in developing countries in reasonable quantities, and within adequate timelines and cost parametres. If companies do not live up to these agreements, then we have march-in rights for the technology as well as background and enabling technology. Approaches include agreements specifying in detail the profit permitted for developing country supply, stipulations that we may seek competitive bids for manufacturing, and partial or full ownership or licensing of the intellectual property by IAVI.
IPS: AIDS vaccine research currently gets about one percent of all global spending on health R D. Do you think that s an appropriate ratio? Is there a funding conflict between HIV/AIDS treatment and prevention?
WARREN: One can only use more. We need more for education, we need more for expanding access to treatment, we need more for vaccines. But even more than the more, we need better. Right now, the financial flows for AIDS vaccines are approaching 800 million dollars a year, and that s more than doubled in the last five years. The projection is that within the next few years, we need to be spending about a billion dollars or so a year, so we re not quite where we need to be, but it s close.
So it s become an issue of spending it better and more wisely. And better spending for me looks like grants and contracts that not only talk about access for the future, but more importantly, in the short-term, guarantee access to data. So for example, when the Gates Foundation made their recent announcement of 300 million dollars over the next five years for AIDS vaccines, within each of those 16 grant contracts were commitments to share data at an early stage. Those kinds of things are the short-term signals that we look to as an advocacy organisation to know that the field is doing science smarter, even if we re not moving as quickly as we would all like in terms of getting answers.
NAYYAR: Actually, we believe that the overall funding landscape in AIDS vaccine development has substantially improved. Yet a comparison of investment in preventive AIDS vaccine R D as a percentage of GDP highlights that countries are not contributing equally. In addition, although pharmaceutical and biotechnology companies are playing a part in AIDS vaccine research today, they are only contributing 10 percent of the total spending from their own resources.
Since industry expertise is so critical to the successful outcome of AIDS vaccine research, IAVI has been working with public and private sector leaders to encourage increased private sector involvement in vaccine R D through a range of innovative incentive programmes. These include advance market commitments, guaranteeing companies would receive a fair price for vaccines developed for poor countries, recently endorsed by the G7 finance ministers.
But it is not about a funding conflict between HIV/AIDS treatment and prevention. Medical advancements for all new promising responses drugs, vaccines and diagnostics are essential if we are to beat back the AIDS pandemic.
IPS: How have clinical trials and research capacity advanced since the early days of AIDS?
WARREN: The good news is when we look at the map of 2006 in terms of where vaccine research is happening compared to five or 10 years ago, it s truly a global effort. There s basic science as well as clinical trials happening not only in the U.S. and Western Europe, but in India, China, South Africa, Uganda, Kenya, the list goes on. And I think the shift from doing research in six countries to 20 countries is for me a testament that the world is getting it better.
Having said that, we are looking at a time in the next three to five years when we are going to have more and hopefully better candidate products that are going to be looking for large-scale efficacy trials needing tens and hundreds of thousands of people, who will go through voluntary counseling and testing, and some of them are going to turn out to be positive and need treatment, and right now we don t have the capacity as a global community to do all of the trials that we are going to need to do.
NAYYAR: First, we know much more about HIV and the way it works in the body than we did in the 1980s. We now know, for example, that virtually all persons immune systems are able to keep the virus in check for a number of years, some for 20 years or more.. There is also good evidence that some rare individuals have a natural ability to avoid HIV infection despite repeated exposure to the virus. Furthermore, experimental vaccines have successfully protected monkeys from simian immunodeficiency virus (SIV), a virus that causes a disease in monkeys much like AIDS.
The field currently has 30 AIDS vaccine candidates in early stage human trials in approximately two dozen countries. Much of this cutting-edge research is being conducted in Africa and Asia, where most new HIV infections are occurring. Over the past couple of years for example, clinical teams from several countries India, China, Rwanda, and Zambia among them have launched the first AIDS vaccine trials in their respective countries, and in doing so increased global site preparations for future AIDS vaccine efficacy trials. Other Phase I and II studies of preventive AIDS vaccines currently underway also stand to significantly inform the field in coming years.
IPS: It seems that one hurdle is the length of time it takes to organise clinical trials, especially as they move toward Phase III. Can and should the process be speeded up, without compromising medical ethics?
WARREN: There are some barriers that just can t be overcome in trials. You have to recruit a lot of people, there are all sorts of things that take time. But there are things that are holding us up unnecessarily. For me, one of the biggest issues we need to be addressing more actively is the regulatory environment. We are talking about trial designs that are very complex, and this is new territory for a lot of people. And we have very long delays. So one thing that we think needs to happen quite urgently is getting the regulatory bodies and community advisory bodies to understand the nature of some of these issues.
We also need trial designs that might get us answers faster. Rather than doing all these trials as compared to a placebo, is there a way to start doing product comparisons earlier in Phase I and Phase II trials to weed out products?
NAYYAR: In IAVI s recently published AIDS Vaccine Blueprint we recommend a new approach to vaccine research which includes an innovative model for moving more novel candidates targeting different immune responses into the pipeline and to accelerating feedback on their efficacy. For example, we believe medium-size proof of concept trials in high-risk populations can quickly yield answers regarding efficacy and safety of AIDS vaccine candidates. This approach would not jeopardise medical ethics all trials will still need to be approved by all relevant agencies in-country but rather ensure we re being much smarter and more targeted in both the research lab and in the field.
IPS: Has it been difficult to overcome the initial public perception in some developing countries that participants were being used as guinea pigs ?
WARREN: Things have changed on three levels. It s changed at the regulatory body level. In several countries Uganda, Kenya, South Africa the very first protocols to be submitted to the regulatory body took up to two years to get approved. It was the first time, people were very nervous. In each of those countries, the second trial protocol was approved in half the time, often within a matter of months.
Two, the policy-making environment is much more supportive when it comes to the second and third trial, because countries begin to buy in to the concept of ownership, that they are part of the development process. Early on, many of the trials appeared to be ones that had been taken on by developed country investigators and research was being done for the developing world. Now people recognise that the Kenyan investigator is a key senior partner in this trial, the South African investigator is the protocol chair, and so on.
Thirdly, it is an issue of the participants themselves. We need to be looking at much more marginalised communities where people are at higher risk. One of the highlights for me of 2006 was the single largest trial in Thailand, which is testing a combination of two different vaccines together. And they completed the recruitment of 16,000 people. So it can be done and we just need to be very sensitive to the fact that recruiting for trials is a hard sell sometimes, and we need to be very responsive to the community.
NAYYAR: There were some groups who raised this question when we started our work in India. However, as the former director of IAVI s India office, and as someone who spent decades working in international public health and reproductive rights in the country, I can say that I don t believe this is the case in India now.
First of all, India is a full partner in AIDS vaccine research. As importantly, for many years, we have worked on the ground in India to ensure the trial process was completely understood at the local level.
Over the years, India has demonstrated its strong capacity to conduct AIDS vaccine candidate trials meeting the highest ethical standards, maintaining complete transparency; and recruiting volunteers through a consultative and inclusive process. Today, we have some of the world s leading AIDS NGOs partnering with us in research.
