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INTERVIEW - Dr. Excler,
Senior Medical Director,IAVI India |
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| AIDS vaccine development faces unprecedented scientific challenges where researchers and developers are still in the dark and progressing with difficulty but determination. … It will take much longer to get the vaccine used for public health intervention and even longer to see a tangible impact of the vaccine on the epidemic. |
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| What are the trends in the spread of AIDS in Asia? Have behavioral change and communication affected the trends? |
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| According to UNAIDS, the number of HIV-infected people was 8.2 million at the end of 2004. Asia shows an extreme diversity in its HIV epidemic, both geographically and temporally. Three categories of countries can be drawn: . |
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1) those that were hit early where now adult prevalence exceeds 1% - e.g. Thailand, Cambodia, Burma and some states in India;
2) those in transition where the epidemic is growing like China, Indonesia, Nepal, and Vietnam;
3) and those with very low prevalence like Bangladesh, Laos, Philippines, and South Korea. |
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China and India represent real threats for the region due to their large population and the heavy burden of the number of HIV-infected people in need for care and treatment.
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| The epidemic has been largely driven by sex work and intravenous drug use. The individuals who are in regular contact and called in the literature “clients” of these two groups are the link to the spouses and the general children being the final link of the chain. For example, in Indonesia, one in two injecting drug users is HIV-infected. Another group where the epidemic is growing and hidden is among men having sex with men. Recent epidemiological studies are highlighting the magnitude of the epidemic in this group. |
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| Significant behavioural changes including fewer casual partners and constant use of condoms have been observed in two countries, Thailand and Cambodia. The response of these two countries is remarkable in their strong political support, very pragmatic, multisectorial, sustained and well-funded large-scale approach. Both countries are Buddhist and have a very compassionate attitude towards HIV-infected people. This factor may be one of the reasons for a positive impact of the response. Thailand and Cambodia provide evidence that classical prevention approaches do work when they are scaled up and endorsed by all. Such positive impact is not seen yet in other countries where greater resolve is lacking and inadequate prevention efforts along with strong stigma allow HIV to reach the general population from high risk groups. This is particularly true for India and China. |
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| Could you brief us on the latest in the preventive technology, with specific reference to vaccines and microbicides? |
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| AIDS vaccine research and development (R&D) is once again at the cross-roads of empiricism and rationale design. We still do not know what the immune correlates of protection are and animal models provide insufficient and sometimes misleading guidance. Several vaccine concept failures and a series of mediocre results have led to a reconsideration of the empirical approach and go back to the bench to redesign AIDS vaccines more rationally. Several new vaccine concepts mainly aiming at inducing a strong cell-mediated response have entered clinical development. The most promising of these vaccine candidates are vectors such as adeno-associated virus, or adenoviruses of various serotypes. Ad5 is the only in clinical trial and others are in the pipeline (11, 35, and chimpanzee-derived). Such approach with Ad5 is currently in test of concept efficacy trial led by Merck. The results of this trial may validate the cell-mediated protective efficacy concept and orient the future axis of development, however it should be recalled that the Merck vaccine includes only a portion of the HIV genes—the envelope gene is lacking and it may be important. |
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| The US NIH VRC is studying a more ‘complete’ Ad5 candidate that is based on HIV subtypes circulating in most of the world – clades* A, B and C. International AIDS Vaccine Initiative (IAVI) is also actively engaged in the research of a vaccine able to induce broad neutralising antibodies with the International Neutralising Antibody Consortium. We think that both cell-mediated and antibody-driven mechanisms are needed for protection. Another set of activities consists in studying early HIV infection and identifying early immune responses and HIV genome sequences that may be of interest for the design of new vaccines. IAVI is undertaking currently several epidemiological and clinical research studies in this regard. |
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| It is important to pursue all feasible methods of prevention, including behaviour change and broad HIV testing to identify HIV-infected individuals. Vaccines, microbicides, male circumcision and treatment with antiretroviral drugs either before or after exposure to infection are all being tested now to determine their efficacy. It is likely that no method alone will suffice. |
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| Is Asia Pacific region as a whole on the agenda? What would be the implications of the availability of preventive technology for the region? |
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| Asia is definitely on the agenda. Is the effort in Asia pushed as it should be for a region that represents 60 per cent of the world population, I would say no. It seems that the major effort is oriented to Africa mainly. There are obvious public health reasons to understand this trend. In addition, some researchers think that epidemiological conditions (high incidences) are more favourable to conduct efficacy trials of new preventive technologies such as microbicides or vaccines in heterosexual and pediatric populations of easy access. It would be unfair and shortsighted to miss the opportunity of accelerating the development and access to new preventive technologies in Asia. Asian countries could join the concert of efforts as those deployed in Africa in defining high risk cohorts needed for efficacy trials. The availability of such technologies in the region would help protecting the high risk populations and their clients and therefore the chain of transmission. But once again, these new technologies must be part of a comprehensive prevention package with classical prevention means along with care and treatment. |
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| Women are said to be affected by HIV/AIDS more than men in terms of sheer numbers. Do you think new technologies would help women and adolescents in Asia? |
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| The proportion of women in the 15-49 year bracket in the HIV-infected adult population in Asia has increased from 20 per cent in 1993 to 30 per cent in 2004. This is still far below Sub-Saharan Africa but nevertheless worrying. Women remain more vulnerable, especially in countries where sex trade and commerce are feeding the epidemic. The other group of women vulnerable to HIV is the spouses of the clients of sex workers. It is therefore quite conceivable that prevention technologies such as microbicides and mechanical “invisible” barriers such diaphragm, and vaccines if proven efficacious will protect and empower women. However, we must be very prudent: these new technologies suffer pitfalls including the need to apply microbicides regularly if not for each sexual act, the tolerance of mechanical devices, the duration of protection of a vaccine, and the fact that protection conferred will highly likely never be 100 per cent. The access to these technologies in a context of stigma and discrimination in particular for women will be another challenge. |
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| We do know that IAVI’s mission is to provide a safe and effective vaccine and make it accessible to all. What is IAVI’s mission and vision for Asia in the coming years? |
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| IAVI is already engaged in AIDS vaccine R&D in India and in advocacy and support activities in China. These activities will be strengthened and hopefully expanded in these two countries. We encourage the expansion of the AIDS vaccine effort in South East Asia whoever the key players are. We believe that India and China require specific attention and that a regional rather than country-specific approach is needed in South East Asia. |
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| Would you justify the vaccine R&D at this point of time given the large deficit in AIDS prevention and care budgets across Asia Pacific region? |
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| Yes definitely and for several reasons. Asia represents 60 per cent of the world population with a growing epidemic. The economic impact of the HIV epidemic is not yet visible but may be dramatic in countries like India, if there is no upsurge for prevention efforts. This a sufficient reason not to slow down the effort. The resource requirement for treatment and care will increase inexorably until we find a way to stop the spread of HIV. The best hope for people already infected with HIV is to prevent new infections, thus sparing resources for their care. |
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| Another reason is scientific. This is principally in Asia that the same AIDS vaccine can be tested in different transmission models including IDU (populations because they are large enough to sustain efficacy trials), hetero- and homo- sexual, and pediatric transmission. Thailand has been an early pioneer in this domain and shown that both classical prevention, vaccine R&D, and care and treatment are all possible in parallel. This creates the critical mass of scientists and public health stakeholders and providers who are able to draw a bigger picture of the epidemic and better lines of action for policy makers. It gives strength and credibility to the overall programme. The research that was conveyed through AIDS vaccine clinical trials in Thailand has benefited to a large number of fields including epidemiological and behavioural trends that guided the prevention efforts and very importantly ownership of research methodology and tools that are now used for care and treatment. This was a deliberate political will of the Thai Government spurred by national champions. The question is not money or “either or”. The question is in the political willingness to move forward the agenda. Most of the funds allocated to AIDS vaccine research are coming from external donors, and their amount is trivial compared to those allocated to care and treatment. AIDS vaccine R&D does not impact negatively on care and treatment and at the contrary can very positively contribute to spur voluntary counseling and testing, risk reduction counselling and access to care and treatment for example in high risk groups targeted for efficacy trials. I like very much the citation of Pandit Nehru who said “this is because we are poor that we cannot afford NOT to do research”. |
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| Would you justify the vaccine R&D at this point of time given the large deficit in AIDS prevention and care budgets across Asia Pacific region? |
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| Yes, definitely. As mentioned earlier, Thailand has been and is still a pioneer in AIDS vaccine development but also in care and treatment. This is the first country to have conducted an efficacy trial in the emerging world and to have initiated a second one. They have paved the way to other countries. China and India have started their first AIDS vaccine trials this year and more is coming. Vietnam, Cambodia and Indonesia have already expressed their willingness to be engaged in this effort. There is, however, not enough cooperation and support from the region and to the region in new preventive technologies. Added to this, international players and donors are sometimes reluctant to engage more ahead for political or ideological reasons including human rights issues or risk of political unrest. I personally think that we should go ahead and tackle the problems when and where they exist rather than say “we cannot work here, too risky”. We cannot be lukewarm to tackle the epidemic. The region has a unique chance to make the difference now in waking up and being bold. |
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| Would you justify the vaccine R&D at this point of time given the large deficit in AIDS prevention and care budgets across Asia Pacific region? |
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| Advocacy has a critical role in highlighting and emphasizing the need for an AIDS vaccine in Asia. The content of the advocacy is even more critical to be credible. AIDS vaccines must be seen as one of the tools for prevention and control of the HIV epidemic along with the classical means of prevention, care and treatment and other potential modern technologies such as microbicides, diaphragm, and pre-exposure prophylaxis. Advocacy must also manage expectations. |
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| The most adapted forms for advocacy in Asia are not an easy fix as Asia is quite diverse. One general feature to keep in mind is that Asian society governance is top-down with some variations though. Advocacy efforts must target first the governments and political leaders. Without their support nothing will move the agenda forward, no matter what are the next advocacy steps. Identifying champions who will advise and offer guidance to the government and stakeholders is also critical. I participated on two occasions in meetings of Asian parliamentarians. Several countries expressed very clearly their interest and wish to engage in AIDS vaccine development such as Vietnam, Cambodia and Indonesia. |
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| Now the issue is more complex when it comes to advocacy with the civil society. You find extremes such as India with many non-governmental and community-based organizations and China with almost none, and in the middle Thailand which has several whose action is limited by top-down governance. |
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| A careful advocacy plan must be country-specific addressing the political and cultural specificities, but it is now of vital interest for these countries to address this issue in a regional manner. Countries may find it easier to actually engage in AIDS vaccine R&D if they feel they are not alone and that neighbouring countries are also joining the effort. |
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| Now coming to the elusive question, when can we expect the vaccine? |
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| AIDS vaccine development faces unprecedented scientific challenges where researchers and developers are still in the dark and progressing with difficulty but determination. If you take the example of classical vaccines such as pediatric combinations developed without specific difficulty by big pharmaceutical companies, the minimum time from concept to market is seven years. Take also the dengue vaccine whose protective concept has been known for years, this vaccine is in now in efficacy trial after more than 15 years of effort. It may hopefully be available within the next 2-3 years. Coming back to AIDS vaccine whose protective concept is still poorly understood and for which clinical development meets tremendous difficulties, it would be misleading to think that because several phase I and II trials are underway or because a “proof of concept efficacy trial” has shown some promises, the vaccine will be on the shelf the “day after” and accessible to all. It will take much longer to get the vaccine used for public health intervention and even longer to see a tangible impact of the vaccine on the epidemic. |
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| Prior to his joining IAVI he was the Chief of the HIV vaccine clinical development for Pasteur Merieux Connaught in France. He combines the rare experience of the pharmaceutical industry, US academic institutions, and of the field in developing countries. He is also consultant for WHO on vaccine R&D. |
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| * Clades (Also called sub-type) A group of related HIV isolates classified by their degree of genetic similarity. There are two major groups of HIV-1 isolates, called M and O. Group M consists of at least eight clades, A through H. (See IAVI AIDS vaccine glossary http://www.iavi.org/viewpage.cfm?aid=34 ) |
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